Differences between oral cancer and cancers of the pharynx and larynx on a molecular level.

In order to elucidate differences between oral cancers and cancers of the pharynx and larynx, we investigated the genetic and epigenetic changes in these tumors using molecular biology methods. Methylation of the promoter region of the p16 tumor suppressor gene was examined using methylation-specific polymerase chain reaction in specimens from 47 oral, 39 pharyngeal and 35 laryngeal squamous cell carcinomas. These specimens were also characterized for allelic loss of certain areas of the genome, i.e., 3p22, 9p21 and 17p13 (TP53). The frequency of methylation of the promoter region of the p16 gene in tongue cancers (35.3%) was significantly higher than in pharyngeal (12.8%) and laryngeal cancers (11.4%) (p=0.046 and p=0.039, respectively). The frequency of methylation in tumors of female patients (47.1%) was significantly higher compared to tumors of male patients (15.4%) (p=0.0067). In contrast, the frequency of the loss of heterozygosity (LOH) at 3p21 in pharyngeal cancers (66.7%) was significantly higher than in oral cancers (20.0%) (p=0.0006). The frequencies of LOH at 17p13 in pharyngeal (71.0%) and laryngeal cancers (73.1%) were also significantly higher than in oral cancers (36.1%) (p=0.009 and p=0.009, respectively). Our results indicate that there are marked differences in the frequencies of the hypermethylation of genes and allelic loss between oral cancers and cancer of the pharynx and larynx. Although all of these tumors were diagnosed as squamous cell carcinomas, the process of carcinogenesis may be different in tumors located in various parts of the head and neck. Loss of function of tumor suppressor genes by allelic loss gives rise to tumors in the pharynx and larynx, while loss of function due to methylation of the promoter regions of those genes is related to carcinogenesis in the oral cavity.