Laryngeal Cancer - Molecular Biology

Overview

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Laryngeal Cancer
  • microRNA mir-1297
  • Gene Expression
  • Glutathione Transferase
  • NAT2
  • Chromosome Aberrations
  • Gene Expression Profiling
  • Loss of Heterozygosity
  • RECQL4
  • Apoptosis
  • Pharyngeal Neoplasms
  • Ploidies
  • Genotype
  • Disease Progression
  • Tissue Fixation
  • Base Sequence
  • Cell Proliferation
  • DNA Methylation
  • Neoplasm Recurrence, Local
  • Case-Control Studies
  • Western Blotting
  • S Phase
  • MicroRNAs
  • Down-Regulation
  • Sequence Deletion
  • CDKN1A
  • Immunohistochemistry
  • Genetic Predisposition
  • BCL2 protein
  • p53 Protein
  • Squamous Cell Carcinoma
  • Neoplasm Invasiveness
  • Cancer DNA
  • Oligonucleotide Array Sequence Analysis
  • bcl-2-Associated X Protein
  • Alcohol Drinking
  • Cancer Gene Expression Regulation
  • DNA-Binding Proteins
  • FISH
  • Mutation
  • Neoplastic Cell Transformation
  • PARK7
  • Lymphatic Metastasis
  • Larynx
  • Head and Neck Cancers
Tag cloud generated 08 August, 2015 using data from PubMed, MeSH and CancerIndex

Mutated Genes and Abnormal Protein Expression (9)

How to use this data tableClicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.

GeneLocationAliasesNotesTopicPapers
TP53 17p13.1 P53, BCC7, LFS1, TRP53 -TP53 and Laryngeal Cancer
124
NAT2 8p22 AAC2, PNAT, NAT-2 -NAT2 and Laryngeal Cancer
11
GSTM3 1p13.3 GST5, GSTB, GTM3, GSTM3-3 -GSTM3 and Laryngeal Cancer
11
CDKN1A 6p21.2 P21, CIP1, SDI1, WAF1, CAP20, CDKN1, MDA-6, p21CIP1 -CDKN1A Expression in Laryngeal Cancer
6
ADH1C 4q23 ADH3 -ADH1C and Laryngeal Cancer
4
RECQL4 8q24.3 RECQ4 -RECQL4 and Laryngeal Cancer
4
PARK7 1p36.23 DJ1, DJ-1, HEL-S-67p -PARK7 and Laryngeal Cancer
3
LMNA 1q22 FPL, IDC, LFP, CDDC, EMD2, FPLD, HGPS, LDP1, LMN1, LMNC, PRO1, CDCD1, CMD1A, FPLD2, LMNL1, CMT2B1, LGMD1B -LMNA and Laryngeal Cancer
3
MIR1297 13 MIRN1297, hsa-mir-1297 -MicroRNA miR-1297 and Laryngeal Cancer
1

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications

Lopes-Aguiar L, Visacri MB, Nourani CM, et al.
Do genetic polymorphisms modulate response rate and toxicity of Cisplatin associated with radiotherapy in laryngeal squamous cell carcinoma?: a case report.
Medicine (Baltimore). 2015; 94(16):e578 [PubMed] Related Publications
UNLABELLED: Cisplatin (CDDP) plus radiotherapy (RT) has been used to treat advanced laryngeal squamous cell carcinoma (LSCC) patients. Single nucleotide polymorphisms (SNPs) may be responsible for differences in chemo/radiosensitivity and side effects in those patients. We reported an advanced LSCC patient, who obtained durable complete response and unexpected pronounced toxicity during CDDP and RT, possibly due to SNPs in genes that modulate the effects of this therapeutic modality.
CASE PRESENTATION: A 30-year-old man with advanced LSCC obtained durable complete response and severe alopecia and pancytopenia after standard and reduced doses of CDDP and RT. Analyses of SNPs revealed that the patient presented GSTT1 deletion, variant MSH3 1045ThrThr, wild GSTP1 105IleIle, and wild BAX -248GG genotypes, which were previously described in association with abnormal detoxification, DNA repair, and damaged cell apoptosis, respectively. Seven other advanced LSCC patients with GSTT1 gene, MSH3 AlaAla or AlaThr, GSTP1 IleVal or ValVal, and BAX GA or AA genotypes served as controls of the study. Only 1 control presented complete response; the other 6 controls obtained partial response of short duration. Four and 3 controls presented grade 1 or 2 and grade 3 anemia or leukopenia during treatment, respectively. The CDDP level in urine collected after CDDP infusion in the reported patient was lower than the median value obtained in controls, suggesting a higher amount of intracellular CDDP in the reported case.The data suggest, for the first time, that inherited abnormalities in intracellular detoxification of CDDP, DNA repair of lesions induced by CDDP and RT, and damaged cell apoptosis may alter treatment response and toxicity in LSCC, but should be confirmed by large pharmacogenomic studies.

Jiang Y, Wang P, Yu Y
[Relationship between the major histocompatibility complex class I chain-related gene A expression and clinicopathologic features in laryngeal squamous carcinoma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014; 28(21):1694-696 [PubMed] Related Publications
OBJECTIVE: To investigate the expression of major histocompatibility complex class I chain-related gene A (MICA) in laryngeal squamous cell carcinoma(LSCC), and its clinical significance.
METHOD: Immunohistochemistry and RT-PCR were used to detect the expression of the MICA in LSCC and normal tissue samples. The relationship between the expression of MICA and the clinicopathologic features features were was analyzed.
RESULT: Compared to the expression of MICA in normal tissues samples, the expression of MICA in LSCC tissue was significantly increased (P < 0.01). MICA expression level in carcinoma tissue was closely related to the tumor-differentiation degree and TNM staging.
CONCLUSION: Our study suggests that MICA may play an important role in the invasion and metastasis of LSCC, and could be a potential tumor maker for LSCC.

Zhou X, Qi Y
[Haplotype analysis of XRCC3 gene and laryngeal].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014; 28(21):1655-7 [PubMed] Related Publications
OBJECTIVE: To explore the association of XRCC3 gene polymorphisms and haplotypes with laryngeal.
METHOD: We selected 4 tag SNPs (rs12432907, rs861536, rs861537, rs861531, rs861531) for the present study. 310 laryngeal patients and 310 healthy control subject were genotyping. The distribution of genotypes and haplotypes in these two group was compared.
RESULT: The distributions of rs12432907 was significantly different between these two groups. The CCAG haplotype frequency was higher in laryngeal group than that in control group. But TCAG and TTAG haplotype frequency was were lower in the laryngeal patient than that those in the control subject.
CONCLUSION: XRCC3 gene polymorphism was associated with the risk of laryngeal patients.

Zhang S, Guo Y, Zhang C, et al.
Primary laryngeal cancer-derived miR-193b induces interleukin-10-expression monocytes.
Cancer Invest. 2015; 33(2):29-33 [PubMed] Related Publications
The pathogenesis of laryngeal cancer (LC) is unclear. Published data indicate that micro RNAs (miRNA) play an important role in the pathogenesis of cancer. This study aims to elucidate the role of miR-193b in the tumor tolerance of LC. High levels of miR-193b were detected in LC cells as well as in the culture supernatant. Interleukin (IL)-10-expressing Mos were detected in the LC tissue-derived single cells. Treating naïve Mos with a miR-193b induced expression of IL-10 in the Mos. Culturing the IL-10(+) Mos with effector CD8(+) T cells resulted in the suppression of CD8(+) T-cell activities.

Starska K, Forma E, Jóźwiak P, et al.
Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer-the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis.
Tumour Biol. 2015; 36(4):2309-21 [PubMed] Free Access to Full Article Related Publications
Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative real-time PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7% of SCC specimens and in 34.4, 59.4, and 62.5% of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p < 0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p < 0.05). SLC2A3 was related to grade and invasion type (p < 0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p < 0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.

Krikelis D, Kotoula V, Bobos M, et al.
Protein and mRNA expression of notch pathway components in operable tumors of patients with laryngeal cancer.
Anticancer Res. 2014; 34(11):6495-503 [PubMed] Related Publications
BACKGROUND: There exist substantial evidence that laryngeal cancer represents a unique entity among squamous head and neck carcinomas.
MATERIALS AND METHODS: Tumors from 289 patients with squamous cell laryngeal cancer were assessed for protein (immunohistochemistry) and mRNA (qRT-PCR) expression of Notch pathway components (Notch1 to 4 receptors and Jagged1 ligand) on tissue microarrays.
RESULTS: In univariate analysis, enhanced nuclear Jagged1 expression conferred a longer disease-free survival (DFS) (p=0.013) and overall survival (OS) (p=0.004), in contrast to the unfavorable prognostic value of Notch3 for both DFS (p=0.009) and OS (p=0.024). In multivariate analysis, overexpression of either Notch or cytoplasmic Jagged1 conferred an unfavorable effect on DFS (Hazard Ratio=1.88, 95% Confidence Interval=1.03-3.43, p=0.04).
CONCLUSION: Our study indicates a consistent unfavorable effect of Notch3 and cytoplasmic Jagged1 protein expression, a favorable impact of nuclear Jagged 1 localization, and a differential prognostic value of Notch2 expression according to the presence of cytoplasmic Jagged 1.

Zhang Y, Liu G, Wang G, et al.
[Prediction of new long non-coding RNA of laryngeal carcinoma by high-throughput RNA-Seq data].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014; 49(8):637-42 [PubMed] Related Publications
OBJECTIVE: To screen and identify the new long non-coding RNAs from transcriptome of laryngeal squamous cell cancer using strand-specific RNA-Seq technology and bioinformatics tools, and to analyze the difference expression of these LncRNAs.
METHODS: RNA was extracted from laryngeal squamous cell cancer tissues of 10 patients and the strand-specific libraries were constructed for high-throughput sequencing. The low-quality data were filtered and the high quality sequencing reads were mapped to the reference genome and assembled. The obtained transcripts were classified and annotated, the optimized LncRNA identification pipeline was used to discover novel LncRNA in these transcriptome, and the characteristics of LncRNA were analyzed.
RESULTS: A more optimized pipeline were established and 134 new LncRNA transcripts were found, which was not included in the public database. The new LncRNA transcripts had some characteristics in length distribution, ORF length, and expression.
CONCLUSION: Some new LncRNA from the transcriptome of laryngeal carcinoma were identified, with different expression, and they may play an important role in laryngeal squamous cell cancer.

Jin J, Lin F, Liao S, et al.
Effects of SNPs (CYP1B1*2 G355T, CYP1B1*3 C4326G, and CYP2E1*5 G-1293C), smoking, and drinking on susceptibility to laryngeal cancer among Han Chinese.
PLoS One. 2014; 9(10):e106580 [PubMed] Free Access to Full Article Related Publications
PURPOSE: This study was conducted to explore the effects of genetic polymorphisms (CYP1B1*2 G355T, CYP1B1*3 C4326G, and CYP2E1*5 G-1293C) and environmental factors (smoking and drinking) on susceptibility to laryngeal cancer in a Han Chinese study group.
METHODS: This case-control study included 552 Han Chinese patients diagnosed with laryngeal cancer and 666 healthy control subjects of the same ethnicity, similar age, and gender. Genetic polymorphisms were examined using multi-PCR and Matrix Assisted Laser Desorption Ionization - Time of Flight (MALDI-TOF MS) methodology. The association of these genetic and environmental factors with susceptibility to laryngeal cancer was evaluated using a statistical approach.
RESULTS: The frequencies of all three polymorphisms in the patient cohort were significantly different from those in the control cohort. Compared to the control cohort, carriers of variant alleles of CYP1B1*2 355T and CYP2E1*5 -1293C showed a higher risk for developing laryngeal cancer (for CYP1B1*2 355T, adjusted OR = 2.657, P <0.001; for CYP2E1*5 -1293C, adjusted OR = 1.938, P <0.001), while carriers of mutation allele CYP1B1*3 4326G showed a lower risk (adjusted OR = 0.562, P <0.001). Joint effects of these polymorphisms were observed. When compared to haplotype G355C4326G-1293, haplotypes T355C4326G-1293 (adjusted OR = 1.809, P <0.001), G355C4326C-1293 (adjusted OR = 1.644, P = 0.044), and T355C4326C-1293 (adjusted OR = 3.104, P <0.001) were associated with a significantly higher laryngeal cancer risk. The adjusted ORs for non-smokers, non-drinkers, smokers, and drinkers with the GT/TT genotype at CYP1B1*2 G355T were 2.190 (P = 0.006), 2.008 (P = 0.001), 5.875 (P <0.001), and 4.518 (P <0.001), respectively.
CONCLUSIONS: CYP1B1*2 355T and CYP2E1*5 -1293C are associated with an increased laryngeal cancer risk, while CYP1B1*3 4326G is associated with a decreased risk. These polymorphisms showed joint effects on laryngeal cancer risk. Smoking and drinking showed collaborative effects with two high risk alleles (CYP1B1*2 355T and CYP1B1*3 4326G) for promoting laryngeal cancer risk.

Braut T, Krstulja M, Rukavina KM, et al.
Cytoplasmic EGFR staining and gene amplification in glottic cancer: a better indicator of EGFR-driven signaling?
Appl Immunohistochem Mol Morphol. 2014; 22(9):674-80 [PubMed] Related Publications
Although enhanced epidermal growth factor receptor (EGFR) signaling has been connected with glottic cancerogenesis, the precise mechanisms of its activation still remain unclear. The aim of the present study was to examine EGFR on protein level, confronting cellular pattern of expression and EGFR gene amplification in glottic carcinomas. Tissue microarray technology was applied for uniformity of results. Biopsy specimens of patients with glottic squamous cell carcinoma and simple hyperplasia (control samples) were immunostained for EGFR. Immunohistochemical EGFR reaction was analyzed as membrane and cytoplasm positive and compared with the presence of gene amplification obtained by fluorescent in situ hybridization (FISH) analysis, obtained previously on a large group of patients. The cytoplasmic distribution of the EGFR staining appeared as a primary property of some squamous carcinoma cells; different from the membranous reaction, the reactions were mutually exclusive. Significantly higher scores of cytoplasmic EGFR staining were found in carcinomas with gene amplification when the cell reaction was examined in the basal and suprabasal layer. Our results suggest that EGFR expression in squamous cell carcinoma is different with regard to tumor cell position in carcinoma with ERGF gene amplification, which could be a new indicator of differently driven EGFR signaling in glottic cancer. Such results with cellular pattern distribution of EGFR protein are worthy of further research.

Luo J, Wu J, Li Z, et al.
miR-375 suppresses IGF1R expression and contributes to inhibition of cell progression in laryngeal squamous cell carcinoma.
Biomed Res Int. 2014; 2014:374598 [PubMed] Free Access to Full Article Related Publications
MicroRNAs (miRNAs) are small noncoding RNA molecules which are involved in tumorigenesis and development. To investigate their role in primary laryngeal squamous cell carcinoma (LSCC), miRNA GeneChips were used to screen the differentially expressed miRNA, and then validated by real-time quantitative PCR in LSCC samples, we found that miR-375 was frequently downregulated in primary LSCC tissues. The tumor-suppressive effect of miR-375 was determined by in vitro assays; through gain-of-function studies we demonstrated that miR-375 can inhibit LSCC cell (SNU-48 and SNU-899) proliferation, motility, and invasion, and promote their apoptosis. In addition, bioinformatics tools TargetScan, PicTar, and Miranda were used to investigate the potential target of miR-375; bioinformatics analysis and dual-luciferase reporter assay indicated that IGF1R was a novel direct target of miR-375. Ectopic transfection of miR-375 led to a significant reduction in IGF1R and its downstream signaling molecule AKT at both the mRNA and protein levels in LSCC cells. Our results suggested that downregulation of miR-375 is one of the molecular mechanisms for the development and progression of LSCC by directly targeting IGF1R and affecting its downstream AKT signaling pathways. Furthermore, miR-375 and IGF1R may serve as a novel therapeutic target for LSCC.

Starska K, Krześlak A, Forma E, et al.
The -5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer.
Toxicol Appl Pharmacol. 2014; 280(2):256-63 [PubMed] Related Publications
Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the -5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region -5 A/G SNP was determined by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2% of SCC and NCM samples, respectively. As a result, a significant association was identified between the -5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed that the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that -5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer.

Song Y, Tian Y, Bai WL, Ma XL
Expression and clinical significance of microRNA-152 in supragalottic laryngeal carcinoma.
Tumour Biol. 2014; 35(11):11075-9 [PubMed] Related Publications
MicroRNAs (miRNAs) are small, noncoding RNAs of endogenous origin that play an important role in tumor development. Here, we examined the role of miR-152 in supragalottic laryngeal carcinoma. The expression of miR-152 was assessed by real-time PCR in tissues from 83 patients with supragalottic laryngeal carcinoma in relation to clinicopathological parameters. Cell viability was assessed by thiazolyl blue assay in Hep-2 cells transfected with miR-152 mimics or a negative control. MiR-152 was significantly downregulated in supragalottic laryngeal carcinoma tissues (t = 12.65, p < 0.001, paired t test), and its expression was correlated with pT stage (χ(2) = 26.88, p < 0.001) and pN stage (z = -3.56, p < 0.001) in patients with supragalottic laryngeal carcinoma. MiR-152 inhibited the proliferation of Hep-2 cells. MiR-152 may serve as a novel prognostic marker in patients with supragalottic laryngeal carcinoma.

Zhang Y, Chen Y, Yu J, et al.
Integrated transcriptome analysis reveals miRNA-mRNA crosstalk in laryngeal squamous cell carcinoma.
Genomics. 2014; 104(4):249-56 [PubMed] Related Publications
Next generation sequencing (NGS) has proven to be a powerful tool in delineating myriads of molecular subtypes of cancer, as well as in revealing accumulation of genomic mutations throughout cancer progression. Whole genome microRNA (miRNA) and mRNA expression profiles were obtained from patients with laryngeal squamous cell carcinoma (LSCC) using deep sequencing technology, and were analyzed by utilizing integrative computational approaches. A large number of protein-coding and non-coding genes were detected to be differentially expressed, indicating a functional switch in LSCC cells. A total of 127 mutated genes were detected to be significantly associated with ectoderm and epidermis development. Eleven miRNAs were found to be differentially expressed, including a potential cancer suppressor miRNA, mir-34c, which was dramatically down-regulated. Integrated analysis of mRNA and miRNA transcriptomes further revealed correlated dynamics among 11 miRNAs and 138 targeted genes, forming a highly dynamical co-regulation network response to LSCC development.

Chen W, Xu L, Wang ZY, et al.
Haplotype analysis of the XRCC1 gene and laryngeal cancer.
Genet Test Mol Biomarkers. 2014; 18(7):525-9 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: Several polymorphisms in DNA repair genes have been extensively studied in association with various human cancers, including laryngeal cancer. The present study aimed to investigate the association between polymorphisms of the XRCC1 gene and laryngeal cancer in a Chinese population.
METHODS: Five polymorphisms of the XRCC1 gene (rs3213403, rs1799778, rs1001581, rs3213282, and rs3810378) were genotyped by TaqMan in 234 patients with larynx cancer and 230 age- and sex-matched controls without cancer.
RESULTS: The rs3213403, rs1799778, and rs3213282 polymorphisms of XRCC1 were associated with larynx cancer. Haplotype analysis indicated that CCA (odds ratio [OR], 5.707; 95% confidence interval [CI], 3.277-9.938; p<0.001), TGG (OR, 4.344; 95% CI, 2.804-6.732; p<0.001), ACA (OR, 1.615; 95% CI, 1.159-2.250; p=0.004), and GCG (OR, 1.702; 95% CI, 1.164-2.489; p=0.005) were associated with an increased risk for larynx cancer, respectively. However, TGA (OR, 0.518; 95% CI, 0.398-0.673; p<0.001) and ACC (OR, 0.314; 95% CI, 0.215-0.457; p<0.001) were associated with a decreased risk for larynx cancer.
CONCLUSIONS: The results indicated that XRCC1 genetic polymorphisms were associated with larynx cancer in a Chinese population.

Starska K, Krześlak A, Forma E, et al.
Genetic polymorphism of metallothionein 2A and risk of laryngeal cancer in a Polish population.
Med Oncol. 2014; 31(7):75 [PubMed] Related Publications
Metallothioneins are intracellular regulators of many biological mechanisms including differentiation, proliferation, angiogenesis and invasion, which are crucial processes in carcinogenesis. This study examines the association between three single-nucleotide polymorphisms at loci -5 A/G (rs28366003) and -209 A/G (rs1610216) in the core promoter region and at locus +838 C/G (rs10636) in 3'UTR region of the metallothionein 2A (MT2A) gene with squamous cell laryngeal cancer (SCLC) risk, as well as with tumor invasiveness according to tumor front grading (TFG). Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism technique in 323 genetically unrelated individuals with SCLC and 418 randomly selected healthy volunteers. Only one SNP (rs28366003) was significantly related to laryngeal cancer in the study population. Compared with homozygous common allele carriers, heterozygous and homozygous for the G variant had significantly increased risk of SCLC [adjusted odds ratio (OR) = 2.90, 95 % confidence interval (CI) 1.53-5.21, p dominant < 0.001]. The A/G allele carriers at rs28366003 MT2A were at higher risk of SCLC development (OR = 2.63, 95 % CI 1.41-2.85, p < 0.001]. There was a significant association between the rs28366003 and stage and TFG classification. Most carriers of minor allele had a higher stage (OR = 2.76, 95 % CI 1.11-7.52, p = 0.03), increased cancer aggressiveness, as defined by a higher total TFG score (>18 points) (OR = 3.76, 95 % CI 1.15-12.56, p = 0.03) and diffuse tumor growth (OR = 5.86, 95 % Cl 0.72-44.79, p = 0.08). The results of this study raise a possibility that a genetic variation of MT2A may be implicated in the etiology of laryngeal cancer in a Polish population.

Zhou X, Qi Y
PLGF inhibition impairs metastasis of larynx carcinoma through MMP3 downregulation.
Tumour Biol. 2014; 35(9):9381-6 [PubMed] Related Publications
Cancer neovascularization plays a key role in the metastasis of larynx carcinoma. However, the molecular mechanism for the neovascularization control in larynx carcinoma is poorly understood. Since placental growth factor (PLGF) has been reported to be involved in pathological angiogenesis, and since matrix metalloproteinases (MMPs) are essential for extracellular matrix degradation during neovascularization, here we were prompted to examine whether PLGF and MMPs may play a coordinate role in the metastasis of larynx carcinoma. Our data showed that the expression of PLGF and MMP3 strongly correlated in the larynx carcinoma in the patients, and significant higher levels of PLGF and MMP3 were detected in the larynx carcinoma from the patients with metastasis of the primary cancer. Thus, we used a human larynx carcinoma cell line, Hep-2, to examine whether expression of PLGF and MMP3 may affect each other. We found that overexpression of PLGF in Hep-2 cells increased expression of MMP3, while inhibition of PLGF in Hep-2 cells decreased expression of MMP3. However, neither overexpression, nor inhibition of MMP3 in Hep-2 cells affected the expression level of PLGF. These data suggest that PLGF may function upstream of MMP3 in larynx carcinoma cells. We then analyzed how PLGF affected MMP3. Application of a specific ERK1/2 inhibitor to PLGF-overexpressing Hep-2 cells substantially abolished the effect of PLGF on MMP3 activation, suggesting that PLGF may increase expression of MMP3 via ERK/MAPK signaling pathway. Since anti-PLGF was recently applied in clinical trials to inhibit cancer-related angiogenesis, here our data further demonstrate that inhibition of cancer neovascularization by anti-PLGF is mediated not only by direct effect on endothelial growth and capillary permeability, but also by indirect effect via MMP3 on the extracellular matrix degradation in larynx carcinoma.

Liu Y, Zhou X, Wen J, et al.
[Inhibition of Hep-2 cell apoptosis after annexin A5 knockdown].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014; 49(4):326-9 [PubMed] Related Publications
OBJECTIVE: To study the effect of annexin A5 on the apoptosis of laryngeal cancer cells.
METHODS: Special siRNAs were used to knock annexinA5 down in Hep-2 cell, and RT-PCR and Western blot were applied to identify the efficacy of RNA interference. The flow cytometry assay was performed to detect the Hep-2 cell apoptosis.
RESULTS: RT-PCR analysis showed that the relative mRNA expression of annexin A5 in siRNA group, negative control group, Lipofectamine 2000 group and blank control group were 0.70 ± 0.03, 1.18 ± 0.05, 1.17 ± 0.06 and 1.23 ± 0.07. The relative mRNA expression of annexin A5 in siRNA group was significantly decreased than contrast groups(t = -14.77, t = -13.23, t = -12.99, P < 0.05).In Western blot assay, the trend of protein expression level was consistent with the mRNA expression levels of annexin A5. The relative levels of proteins in siRNA group, negative control group, Lipofectamine 2000 group and blank control group were shown 1.21 ± 0.03, 3.88 ± 0.06, 3.87 ± 0.02 and 3.95 ± 0.08. The relative protein expression of annexin A5 in siRNA group was significantly decreased than contrast groups(t = -70.34, t = -150.62, t = -56.32, P < 0.05). At the same time in flow cytometry the apoptotic rate of siRNA group, negative control group, Lipofectamine 2000 group and blank control group were 4.43% ± 0.12%, 13.67% ± 0.22%, 13.66% ± 0.12% and 13.35% ± 0.13%, the difference between the siRNA group and contrast groups was statistically significant(t = -62.50, t = -14.16, t = -11.47, P < 0.05).So after RNA interference, expression of annexin A5 decreased, and the results in the apoptosis inhibition of Hep-2 cell.
CONCLUSION: Annexin A5 promotes apoptosis of Hep-2 cells, and it may be a potential therapeutic target for the laryngeal cancer.

Song Y, Dong YD, Bai WL, Ma XL
Silencing of Src by siRNA inhibits laryngeal carcinoma growth through the Src/PI-3 K/Akt pathway in vitro and in vivo.
Tumour Biol. 2014; 35(9):9009-14 [PubMed] Related Publications
This study aimed to investigate the expression, function, and possible mechanism of Src in the Hep-2 cell line. We used Src-specific small interfering RNA (siRNA) to inhibit the expression of Src in Hep-2 cells. RT-PCR and Western blot were applied to evaluate the expression level of Src after RNA interference, and the MTT assay and flow cytometry were used to observe the expression of PI-3 K and Akt. siRNA can downregulate the expression of Src in Hep-2 cells. Downregulation of Src decreased PI-3 K and Akt expression. We found that Src knockdown inhibits the proliferation of Hep-2 cells and the growth of laryngeal carcinoma in vivo. This study has demonstrated that Src participates in the regulation of apoptosis through the Src/PI-3 K/Akt signaling pathway in the Hep-2 cell line. Silencing of Src by siRNA is a viable approach in laryngeal carcinoma treatment.

Li Q, Liu M
Glutathione S-transferase T1 null genotype and laryngeal cancer risk: a meta-analysis.
Tumour Biol. 2014; 35(9):8781-5 [PubMed] Related Publications
Glutathione S-transferase T1 (GSTT1) polymorphic variation has been implicated as a risk factor for various cancers. However, previous studies investigating the association between GSTT1 null genotype and laryngeal cancer risk in Asians reported conflicting outcomes. In the present study, the possible association of laryngeal cancer risk with GSTT1 null genotype was explored by a meta-analysis. Relevant studies were identified through a systemic search of PubMed and Chinese National Knowledge Infrastructure databases. Six studies with a total of 1,824 individuals were included in the meta-analysis. The pooled odds ratio (OR) with 95 % confidence interval (CI) was used to assess the association. Meta-analysis of all included studies showed that there was an obvious association between GSTT1 null genotype and laryngeal cancer risk in Asians (OR = 2.41, 95 % CI 1.27-4.57, P = 0.007, I (2) = 86 %). After adjusting for heterogeneity, there was still an obvious association between GSTT1 null genotype and laryngeal cancer risk in Asians (OR = 1.75, 95 % CI 1.36-2.24, P < 0.001, I (2) = 0 %). The findings from the meta-analysis suggest that GSTT1 null genotype is associated with laryngeal cancer risk in Asians.

Foteinou E, Kontos CK, Giotakis AI, Scorilas A
Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma.
Biol Chem. 2014; 395(9):1051-62 [PubMed] Related Publications
Several members of the family of tissue kallikrein and kallikrein-related peptidases have been suggested as promising tumor biomarkers with important prognostic significance. However, only one (KLK11) has already been studied in laryngeal squamous cell carcinoma (LSCC) as a potential biomarker for LSCC diagnosis and/or prognosis. Our study investigated the prognostic value of kallikrein-related peptidase-4 (KLK4) mRNA expression as a molecular tissue biomarker in LSCC. For this purpose, KLK4 mRNA expression analysis was performed in 116 cancerous and 74 paired non-cancerous laryngeal tissue specimens obtained from patients that had undergone surgical treatment for primary LSCC. A remarkable downregulation of KLK4 mRNA expression was discovered in laryngeal tumors, compared to non-cancerous laryngeal tissue specimens. KLK4 mRNA expression was also shown to distinguish LSCC from non-cancerous laryngeal tissues. Furthermore, low KLK4 mRNA expression was shown to predict poor disease-free survival, independently of the histological grade and size of the malignant tumor as well as patient TNM stage. According to Kaplan-Meier survival analysis, low KLK4 mRNA expression predicts short-term relapse even among patients with well-differentiated tumors or those at an early TNM stage. Thus, KLK4 mRNA positivity could be regarded as a novel independent indicator of favorable prognosis for the disease-free survival of LSCC patients.

Wang R, Ma H, Lian M, et al.
[A preliminary study on genome-wide expression profiling of laryngeal squamous cell carcinoma].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014; 49(3):232-5 [PubMed] Related Publications
OBJECTIVE: To identify the genes differentially expressed and underlying molecular mechanism in laryngeal squamous cell carcinoma by using cDNA microarrays.
METHODS: Using Illumina Human HT-12 BeadChip, gene expressions were detected in ten pairs of laryngeal cancer tissues and adjacent normal tissues. Total RNA was extracted and reverse-transcribed into cDNA. Labeled cDNA were hybridized with cDNA microarray, data were read and images were scanned. All the samples had passed quality control testing.
RESULTS: Through Illumina Genomstudio 1.9.0 Data processing software (P < 0.05 or diffscore>13, diffscore<-13) and multiple displacement t test(FDR<0.05), 426 genes showed statistically significant differences in expressions between laryngeal tumor tissues and corresponding adjacent normal tissues, with 222 up-regulated genes and 204 down-regulated genes in laryngeal cancer tissues. These up- or down-regulated genes were indicated to involve in cellular processes relevant to the cancer phenotype, such as proliferation, cell cycle, chromosome segregation, mitosis and meiosis. These differentially expressed genes also took part in cancer related signaling pathways as well, for instance, metabolic pathways, cell cycle, DNA replication, glutathione metabolism, mucin type O-Glycan biosynthesis, drug metabolism-cytochrome P450 and so on.
CONCLUSION: The set of genes identified here and their functional annotations contribute to a better understanding of the pathogenesis of laryngeal squamous cell carcinoma from the view of multiple gene interactions and provide candidate markers for improving diagnosis, prognosis and treatment of this cancer.

Li M, Tian L, Yao H, et al.
ASAP1 mediates the invasive phenotype of human laryngeal squamous cell carcinoma to affect survival prognosis.
Oncol Rep. 2014; 31(6):2676-82 [PubMed] Related Publications
ASAP1 helps regulate cellular structures such as actin cytoskeletal remodeling and focal adhesions that have a pivotal function in tumor progression. Overexpression of ASAP1 has proven to be a malignant indicator for a variety of tumors. To further determine the potential involvement of ASAP1 in laryngeal squamous cell carcinoma (LSCC), we evaluated the expression levels of ASAP1 by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry in tissue samples of 64 LSCC patients. We then analyzed and correlated the results with clinicopathological features. Furthermore, we used small interfering RNA (siRNA) to inhibit ASAP1 expression in vitro. The potential function of ASAP1 in invasiveness was evaluated in the Hep-2 LSCC cell line. Kaplan-Meier method was utilized to determine the association of ASAP1 expression with survival of patients. We showed that ASAP1 was upregulated in primary LSCC tumors and was correlated with lymph node metastasis and clinical tumor stage. Similarly, higher levels of ASAP1 were detected in the Hep-2 cell line compared to the 16 human bronchial epithelial (16HBE) cell line. ASAP1 expression was downregulated by lentiviral vector transfection containing siRNA in vitro. The invasive potential of these cells was found to be significantly suppressed, while expression levels of Rac1 and Cdc42 positively correlated with the inhibition of ASAP1 expression. In Kaplan-Meier overall survival curves, higher ASAP1 mRNA levels were found to be associated with a shorter progression-free survival trend. Based on these results, ASAP1 appears to contribute to the malignant mechanism of LSCC and may represent a significant prognostic marker for LSCC patients.

Kis A, Tatár TZ, Gáll T, et al.
Frequency of genetic and epigenetic alterations of p14ARF and p16INK4A in head and neck cancer in a Hungarian population.
Pathol Oncol Res. 2014; 20(4):923-9 [PubMed] Related Publications
Occurrence of genetic and epigenetic alterations affecting p14ARF and p16INK4A were investigated in tumour samples of 37 oral (OSCC) and 28 laryngeal squamous cell cancer (LSCC) patients, and compared to exfoliated buccal epithelial cells of 68 healthy controls. Presence of deletions and mutations/polymorphisms affecting exons were examined using sequencing. Methylation status of promoters was assessed by methylation-specific PCR. Chi-square and Fisher's exact tests were used to compare frequency of events. Exon deletions were found in four controls, one OSCC and 22 LSCC patients; the latter significantly differed from controls (p < 0.001). Only two mutations (T24610A and C24702A) were in p16 exon 1 of two OSCC patients. Polymorphisms G28575A (Ala140Thr), G31292C (C540G) and G28608A were found in both patient groups. The p14 promoter was unmethylated in 86.7 % of OSCC and in 85.7 % of LSCC patients; for the p16 promoter these rates were 69.0 % and 76.2 % for OSCC and LSCC patients, respectively. Combining the two patient groups, unmethylated promoter was significantly less frequent in case of both p14 and p16 (p = 0.043 and p = 0.001, respectively) compared to the control group. In summary, exon deletion may be important in LSCC, while promoter methylation was relatively frequent in both patient groups.

Yang N, Hui L, Wang Y, et al.
SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway.
Oncol Rep. 2014; 31(6):2651-9 [PubMed] Related Publications
SOX2 is a high mobility group box containing transcription factor that has been reported to be aberrantly overexpressed in various human malignancies, including laryngeal squamous cell carcinoma (LSCC). However, the potential role of SOX2 in LSCC migration and invasion remains to be elucidated. In the present study, we generated stable transformants of human LSCC cells constitutively overexpressing SOX2 and investigated the effects of SOX2 overexpression on migration and invasion in LSCC cells as well as the possible underlying mechanisms. We found that ectopic overexpression of SOX2 in LSCC cells enhanced their migratory and invasive ability in vitro, accompanied by increased expression and activity of matrix metalloproteinase (MMP)-2. Meanwhile, SOX2-induced cell migration and invasion were significantly abrogated by a neutralizing anti-MMP-2 antibody or small interfering RNA targeting MMP-2. Furthermore, overexpression of SOX2 induced phosphorylation of Akt and mammalian target of rapamycin (mTOR), which are downstream effectors of the PI3K pathway. Finally, LY294002, an inhibitor of PI3K, also markedly abolished SOX2-induced activation of the Akt/mTOR pathway and increased cell invasion and MMP-2 expression. Taken together, we conclude that SOX2 promotes migration and invasion of laryngeal cancer cells by inducing MMP-2 via the PI3K/Akt/mTOR pathway. Our findings suggest that SOX2 may serve as a potential therapeutic target for LSCC.

Zhang T, Han G, Wang Y, et al.
MicroRNA expression profiles in supraglottic carcinoma.
Oncol Rep. 2014; 31(5):2029-34 [PubMed] Related Publications
MicroRNAs (miRNAs) are single-stranded RNA molecules which regulate gene expression at the post-transcriptional level and several miRNAs have been found to be associated with some types of cancer. We sought to identify the expression and involvement of miRNAs in supraglottic carcinoma tissues compared with normal tissues and to determine whether miRNA expression is predictive of disease. Unsupervised clustering shows that miRNA profiles can distinguish tumor from normal tissues. Analysis of miRNA contents in supraglottic carcinoma highlighted nineteen differentially expressed miRNAs, three upregulated miRNAs (miR-21, miR-19a, miR-33a) and two downregulated miRNAs (miR-206, miR-375). The microarray results of supraglottic carcinoma and related computer analysis may be beneficial for further analysis of cancer diagnosis and therapy.

Wang DS, Lai HC, Huang JM
Epidermal growth factor receptor mutations in Chinese patients with laryngeal squamous cell carcinoma.
Acta Otolaryngol. 2014; 134(6):631-5 [PubMed] Related Publications
CONCLUSION: The epidermal growth factor receptor (EGFR) mutation is rare in patients with laryngeal squamous cell carcinoma (LSCC) in China.
OBJECTIVE: To determine the incidence of EGFR mutations in patients with LSCC who underwent surgical resection in mainland China.
METHODS: xTAG technology was used to detect the EGFR exon 19, exon 20, and exon 21 mutations in 132 patients with LSCC who underwent surgical treatment in our hospital from 2010 to 2013.
RESULTS: Of the 132 LSCC specimens examined, only 1 specimen was found to be positive for EGFR exon 20 mutation (0.76%). The mutation was p.T790M in exon 20. Two LSCC specimens were positive for EGFR exon 21 mutation (1.52%). The mutation was p.L858R in exon 21. None of the samples was found to be positive for EGFR exon 19 mutation.

Zhang Y, Chen W, Ji JF, et al.
GSTM1 null polymorphisms is associated with laryngeal cancer risk: a meta-analysis.
Tumour Biol. 2014; 35(7):6303-9 [PubMed] Related Publications
Many studies have examined the association between the GSTM1 (null or non-null genotype) polymorphism and laryngeal cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. PubMed was searched for case-control studies published up to December 2013. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 23 studies, comprising 2,562 laryngeal cancer cases and 4,091 controls, were included. Overall, for null versus present, the pooled OR was 1.22 (95 % CI = 1.10-1.36), and the heterogeneity was found in all studies. In the stratified analysis by ethnicity, significant risks were found among Asians (OR = 1.71; 95 % CI = 1.34-2.19; P = 0.011 for heterogeneity) and in Caucasians (OR = 1.13, 95 % CI = 1.00-1.27; P = 0.036 for heterogeneity). In conclusion, this meta-analysis demonstrates that the GSTM1 null gene polymorphism is an increased risk of laryngeal cancer in Asians and Caucasians.

Tian S, Xiao Q, Zhang J, et al.
[The association between genetic polymorphisms of DNA repair genes XPD, XPC and susceptibility to laryngeal carcinoma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2013; 27(21):1199-205 [PubMed] Related Publications
OBJECTIVE: To analyze the association between genetic polymorphisms of DNA repair genes of XPD (751 Lys/Gln), XPC (PAT)and susceptibility to laryngeal carcinoma. To explore the effect between DNA repair genes of XPD (751 Lys/Gln), XPC (PAT) and carcinogenesis of LSCC(laryngeal squamous cell carcinoma).
METHOD: A case-control study was conducted involving 233 LSCC patients and 102 healthy controls to investigate the association between polymorphisms of XPD(751 Lys/Gln), XPC (PAT) and LSCC. All blood samples of the Han people from the Guang Dong Zone was analysze with methods of PCR, PCR-RFLP, ASA and the technique of checking DNA sequencing with sequenator. We explored the association between polymorphisms and the clinical pathologic characteristic of LSCC. The data was compute with SPSS13.0. Odds Ratios (ORs) with 95% CI for relevancy intensity were calculated using binary logistic regression analysis. REULT: There is no difference of the frequency of XPC-PAT and XPD (751 Lys/Gln) genotype between in LSCC and in healthy contradistinguish (P > 0.05).
CONCLUSION: There may be no association between the susceptibility to laryngeal carcinoma and the genotype of XPC-PAT and XPD (751 Lys/Gln).

Bergshoeff VE, Van der Heijden SJ, Haesevoets A, et al.
Chromosome instability predicts progression of premalignant lesions of the larynx.
Pathology. 2014; 46(3):216-24 [PubMed] Related Publications
The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice. Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and 7 centromeres was performed on tissue sections of laryngeal premalignancies in 69 patients. Chromosome instability was indicated by numerical imbalances and/or polysomy for chromosomes 1 and 7. Additionally, immunostainings for p53, Cyclin D1 and (p)FADD expression were evaluated. Malignant progression was recorded. Eighteen patients with carcinoma in situ (CIS) were treated after diagnosis and excluded from follow-up. Chromosome instability was strongly associated with a high risk of malignant transformation, especially in lower grade lesions (hyperplasia, mild and moderate dysplasia; odds ratio = 8.4, p = 0.004). Patients with lesions containing chromosome instability showed a significantly worse 5-year progression-free survival than those with premalignancies without chromosome instability (p = 0.002). Neither histopathology nor the protein markers predicted progression in univariate analysis, although histopathological diagnosis, p53 and FADD contributed positively to chromosome instability in multivariate analysis. Chromosome instability is associated with malignant progression of laryngeal premalignancies, especially in lower grade lesions. These results may contribute to better risk counselling, provided that they can be validated in a larger patient set.

Lu B, Li J, Gao Q, et al.
Laryngeal cancer risk and common single nucleotide polymorphisms in nucleotide excision repair pathway genes ERCC1, ERCC2, ERCC3, ERCC4, ERCC5 and XPA.
Gene. 2014; 542(1):64-8 [PubMed] Related Publications
Because the molecular mechanisms underlying the development of laryngeal cancer are not well understood, we conducted a case-control study to determine the association between eight common SNPs in NER pathway genes and risk of laryngeal cancer, and the association between genetic polymorphisms and environmental factors. A 1:1 matched case-control study of 176 cases and 176 controls was conducted. Laryngeal cancer cases were more likely to smoke and drink (all P values<0.05). Subjects with the ERCC1 rs11615 CC genotype and C allele had an increased risk of laryngeal cancer. Similarly, individuals with the ERCC5 rs17655 GG genotype and G allele had an increased risk of laryngeal cancer. Gene-gene interaction analysis showed that subjects carrying ERCC1 rs11615 C allele and XPG/ERCC5 rs17655 G allele had a greatly increased risk of breast cancer. Stratified analysis revealed that the interaction between polymorphisms of ERCC1 rs11615 and ERCC5 rs17655 and smoking on cancer risk was statistically significant, and ERCC1 rs11615 polymorphisms also had a significant interaction with drinking habit. In conclusion, our study suggests that ERCC1 rs11615 and ERCC5 rs17655 polymorphisms are associated with increased risk of laryngeal cancer, and that they confer more risk among smokers and drinkers.

Recurring Structural Abnormalities

Selected list of common recurrent structural abnormalities

Abnormality Type Gene(s)
8p23 Loss in Laryngeal Cancer

This is a highly selective list aiming to capture structural abnormalies which are frequesnt and/or significant in relation to diagnosis, prognosis, and/or characterising specific cancers. For a much more extensive list see the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.

8p23 Loss in Laryngeal Cancer

Jin C, Jin Y, Wennerberg J, et al.
Nonrandom pattern of cytogenetic abnormalities in squamous cell carcinoma of the larynx.
Genes Chromosomes Cancer. 2000; 28(1):66-76 [PubMed] Related Publications
Cytogenetic analysis of short-term cultures from 105 squamous cell carcinomas of the larynx (LSCC) revealed clonal chromosome aberrations in 56 tumors. Simple karyotypic changes (less than four aberrations per clone) were found in 24 cases, and the remaining 32 tumors had complex karyotypes with multiple numerical as well as unbalanced structural rearrangements. Extensive intratumor heterogeneity, in the form of multiple related subclones or unrelated clones, was observed in a large fraction of the tumors. The structural changes most often affected chromosomes 3, 1, 11, 7, 2, 15, 5, 4, 8, and 12, with rearrangements in the centromeric regions, i.e., the centromeric bands p10 and q10 and the juxtacentromeric bands p11 and q11, accounting for 43% of the total breakpoints. The most common imbalances brought about by numerical and unbalanced structural rearrangements were loss of chromosomal region 3p21-pter, chromosome arms 4p, 6q, 8p, 10p, 13p, 14p, 15p, and 17p, and gain of chromosomal regions 3q21-qter, 7q31-pter, and 8q. Among 17 recurrent aberrations identified, the most common were i(8q), hsr(11)(q13), i(3q), i(5p), and del(3)(p11). No statistically significant association was found between major karyotypic features and histological differentiation or TNM stage. The karyotypic features of the LSCC were also compared with previously published oral SCC, a subgroup of SCC that has been more extensively characterized cytogenetically. No clear-cut karyotypic differences were found between LSCC and oral SCC, with the exception that i(8q) was significantly more frequent among the latter.

Scholnick SB, Haughey BH, Sunwoo JB, et al.
Chromosome 8 allelic loss and the outcome of patients with squamous cell carcinoma of the supraglottic larynx.
J Natl Cancer Inst. 1996; 88(22):1676-82 [PubMed] Related Publications
BACKGROUND: Loss of genetic heterogeneity (allelic loss or loss of heterozygosity) on chromosome arm 8p is frequent in squamous cell carcinomas of the head and neck and has been associated with poor prognosis. We have previously demonstrated that there are three minimal regions of allelic loss on this chromosome arm. The location of each region is marked by a microsatellite locus: D8S264 (8p23), D8S552 (8p23-p22), and D8S133 (8p21). These findings imply the existence of at least three putative tumor suppressor genes on this chromosome arm that may become inactivated during the progression of squamous cell carcinoma.
PURPOSE: We used allelic loss data from these three loci to determine if inactivation of these putative suppressors is associated with poor prognosis for patients with squamous cell carcinoma of the supraglottic larynx. We also used multivariate statistics to compare the prognostic power of allelic loss at these genetic markers with that of demographic, clinical, and histopathologic parameters.
METHODS: We examined the D8S264, D8S552, and D8S133 microsatellites in tumors from a retrospective population of 59 patients. All patients had histologically confirmed squamous cell carcinoma of the supraglottic larynx and had been treated surgically. DNA was extracted from matched sets of normal and microdissected tumor tissue and used for polymerase chain reaction amplification of the microsatellite markers. Reaction products were separated by denaturing gel electrophoresis and visualized by autoradiography. Patient data were obtained from the original pathology report and from the tumor registry of the Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO. Histopathologic data were obtained by reviewing the portion of the resection specimen used for DNA extraction. Parameters whose association with reduced disease-free interval and reduced disease-specific survival was statistically significant were identified by use of the Kaplan-Meier method and the logrank statistic. Multivariate Cox proportional hazards models were used to identify independent predictors of poor prognosis. All statistical tests were two-sided.
RESULTS: In this patient population, allelic loss at the D8S264 locus was associated with both shorter disease-free interval (logrank P = .028) and reduced disease-specific survival (logrank P = .004). Allelic loss at the next most centromeric locus, D8S552, had a statistically significant association with only reduced disease-specific survival (logrank P = .034), whereas allelic loss at the most centromeric region, D8S133, showed no statistically significant association with reductions in either interval. Multivariate Cox models suggested that D8S264 was the only 8p marker of the three microsatellites with a statistically significant and independent association with shortened disease-free interval (relative risk [RR] = 3.38; P = .0107) and reduced disease-specific survival (RR = 3.41; P = .0105).
CONCLUSIONS: Allelic loss in the p23 region of chromosome 8 appears to be a statistically significant, independent predictor of poor prognosis in patients with supraglottic squamous cell carcinoma.

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