Detection of ERBB2 (Her2/neu) and P16 (INK4A) genes in oral squamous cell carcinoma using fluorescent in situ hybridization (FISH)


Background Head and neck cancers account for approximately 5% of all carcinomas in industrialized countries, witha worldwide incidence of 500,000 new cases annually. Nearly all head and neck cancers (90%) are squamous cellcarcinomas (SCCs), and >50% of tumors arise in the oral cavity. It is important to know what prognostic factors canfacilitate diagnosis, optimize therapeutic decisions, and improve the survival of these patients. A member of theepidermal growth factor receptor (EGFR) family, HER2/neu, has received much attention because of its therapeuticimplications. The p16 gene produces P16 protein, which in turn inhibits phosphorylation of Rb, thus inhibiting the Rbinducedrelease of transcription factor EF1 and cell cycle progression. Genetic aberration analyzed by fluorescence(FISH) to measure the gene copy number. The aims of the present study are to detect HER2/neu amplification andP16 deletion in oral squamous cell carcinoma and correlate them with various clinicopathological parameters (age,sex, clinical presentation, tumor site, tumor stage, tumor grade).Materials and Methods Thirty formalin-fixed paraffin embedded tissue blocks of oral squamous cell carcinoma whichwere collected from laboratories archives included in this study. H&E stain was done for each block for reassessmentof histological examination. DNA probes were used to detect copy numbers of the HER2/neu and P16 genes usingfluorescent in situ hybridization technique (FISH).Results FISH evaluation showed that HER2/neu gene amplification was found in 12 cases (40%), while 18 cases (60%)showed no amplification. Among the cases in which amplification was not found, 8 cases (44.45%) showed polysomyof chromosome 17.P16 gene deletion was found in 20 cases (66.7%) while 10 cases (33.3%) showed no deletion.Conclusions: HER2/neu amplification and P16 deletion were observed in studied oral squamous cell carcinomasamples using FISH, however, statistically non significant correlation with all clinicopathological findings (age, sex,clinical presentation, tumor site, tumor stage, tumor grade) and also between both genes were found in the presentstudy. It is premature to conclude that HER-2/neu and P16 alterations may have prognostic significance, but it is alsotoo early to dismiss that possibility without a larger, perhaps multicenter study