RESUMEN
BACKGROUND: Mucins are high-molecular-weight glycoproteins and are implicated in diverse biological functions. MUC4, a member of transmembrane mucin family, is expressed in airway epithelial cells and body fluids such as the saliva, tear film, ear fluid and breast milk. In addition to its normal expression, an aberrant expression of MUC4 has been reported in a variety of carcinomas. Till date, very few studies have discussed about MUC4 expression in normal and cancerous oral mucosa. AIM: The aim of the study is to evaluate the expression of MUC4 in varying grades of oral squamous cell carcinoma (OSCC) and also to analyze its role played in oral carcinogenesis. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissues of five cases of normal tissue, ten cases of well-differentiated OSCC, ten cases of moderately differentiated OSCC and ten cases of poorly differentiated OSCC were retrieved from the archives of the department, and MUC4 antigen was immunohistochemically localized. STATISTICAL ANALYSIS: The result was subjected to statistical analysis using Pearson's Chi-square test and one-way analysis of variance. RESULTS: About 70% of OSCC were stained positive with MUC4 antigen. Maximum intensity of staining was noted in well-differentiated OSCC. A steady decrease in MUC4 staining was noted with the increase in histological grading of OSCC. CONCLUSION: The findings of the study suggest that MUC4 plays a vital role in the pathogenesis of OSCC and can be regarded as a novel marker for OSCC.
RESUMEN
BACKGROUND AND OBJECTIVES: To investigate a potential association between single-nucleotide polymorphisms (SNPs) and haplotypes at the TNFA-LTA locus and the development of oral cancer in an Indian population. MATERIALS AND METHODS: In this study, 150 oral precancer/cancer samples (50 precancer and 100 cancer), along with an equal number of control samples, were genotyped. Six SNPs at the TNF-LTA locus (i.e., -238G/A, -308G/A, -857C/T, -863C/A, -1031T/C, and +252A/G) were analyzed by use of a polymerase chain reaction-restriction fragment length polymorphism method, the assay was validated by sequencing 10 % of samples. RESULTS: The allelic frequencies of TNFA and LTA SNPs were found to be significantly associated with the risk of oral cancer and precancerous lesions in comparison with controls (P < 0.0003). Further haplotypic analysis showed that two haplotypes (ATCTGG and ACACGG) served as risk haplotypes for oral cancer. These haplotypes were also found to be significantly and positively associated with lifestyle habits (tobacco chewing P = 0.04, odds ratio [OR] 3.4) and socioeconomic status (P = 0.01, OR 3.4). We noticed an increased percentage of risk haplotypes correlating with the aggressiveness of oral cancer. The percentages of risk haplotypes were found to be threefold higher in precancer and fourfold higher in advanced stages of oral cancer in comparison with controls. CONCLUSION: Five SNPs at the TNF-LTA locus (i.e., -308G>A, -857C>T, -863C>A, -1031T>C, and +252A>G) were found to be associated with the development of oral cancer. Two haplotypes (ATCTGG and ACACGG) emerged as major risk haplotypes for oral carcinoma progression and were also found to be associated with lifestyle factors and clinical aggressiveness. These findings make the TNF-LTA locus a suitable candidate for a future biomarker, which may be used either for early detection or for helping to improve treatment efficacy and effectiveness.