To identify genes that could potentially serve as molecular therapeutic markers for human head and neck cancer (HNC), we employed differential display analysis to compare the gene expression profiles between HNC and histopathologically normal epithelial tissues. Using reverse transcription-polymerase chain reaction and Western blot analysis, desmoglein 3 (DSG3) was identified as being differentially expressed at both the RNA and protein levels. Of 56 patients assayed, 34 (61%) had overexpression of DSG3, which correlated statistically with T stage (P ¼ 0.009), N stage (P ¼ 0.047), overall stage (P ¼ 0.011), tumor depth (P ¼ 0.009) and extracapsular spread in lymph nodes (P ¼ 0.044), suggesting that DSG3 participates in carcinogenesis of HNC. Consistent with the clinical findings, inhibition of DSG3 by RNA interference (RNAi) significantly reduced cell growth and colony formation to 57-21% in three HNC cell lines. Use of an in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 30-48% in three cell lines tested. An in vivo xenograft study showed that administration of DSG3-RNAi plasmid significantly inhibited tumor growth for 2 months in BALB/C nude mice. In conclusion, DSG3 is identified overexpressed in HNC, with the degree of overexpression associated with clinicopathologic features of the tumor. Inhibition of DSG3 significantly suppresses carcinogenic potential in cellular and in vivo animal studies. These findings suggest that DSG3 is a potential molecular target in the development of adjuvant therapy for HNC.

Although several studies have found overexpression of epidermal growth factor receptor (EGFR) proteins EGFR and Her-2 in head and neck cancers, the clinical relevance of the finding varies. We examined the expression and clinical association of these molecules with oral squamous cell carcinoma in an area where betel chewing is prevalent. EGFR and Her-2 proteins were measured in 59 paired (grossly normal and cancer) tissues by an enzyme immunoassy method. The cutoff value for gene overexpression was defined as the level of mean expression in normal tissue plus two s.d. A total of 59% of the patients consumed alcohol, 90% smoked tobacco, and 90% chewed betel quid. Of the patients assayed, 34 (58%) and 24 (41%) had EGFR and Her-2 overexpression, with average 3.5-and 1.5-fold elevations. EGFR overexpression has been shown to be statistically associated with T stage, N stage, overall TMN stage, primary tumour depth, lymph node extra-capsular spread, and poor survival. Her-2 overexpression, however, did not demonstrate a similar association with clinicopathological parameters or therapeutic outcome. On multivariant analysis, EGFR overexpression (P ¼ 0.041) and N stage (P ¼ 0.024) were the only independent factors for overall survival. These results indicate that the molecular targeting therapy to EGFR may be a treatment for oral cavity cancer in the betel quid-chewing prevalent area.

The present study was designed to examine whether different p53 haplotypes of exon 4 -intron 3 -intron 6 affect the frequency of mutations and loss of heterozygosity (LOH) of the p53 gene in male oral squamous cell carcinomas (OSCCs) in Taiwan. We found that individuals without two Pro-W-G alleles had significantly higher frequency of p53 mutations than those with two Pro-W-G alleles (odds ratio (OR) ¼ 1.98; 95% confidence interval (CI), 1.10 -3.56). Out of the 172 p53 gene exon 4 informative male OSCCs, 72 (41.9%) showed LOH. Among these 72 OSCCs with LOH, the frequency of Pro allele loss was 73.6% (53/72). It is notable that alcohol drinking increased the frequency of Arg allele loss (OR ¼ 10.56; 95% CI, 1.23 -234.94) in OSCCs from patients who both smoked cigarettes and chewed areca quid (AQ). The frequency of LOH of p53 was not different between p53-mutated OSCCs and p53-normal OSCCs. Thus, the present study revealed that (a) the Arg allele is associated with p53 mutations, (b) the Pro allele is preferentially lost in OSCCs associated with cigarette smoking and AQ chewing, while the frequency of Arg allele loss is increased with alcohol drinking, and (c) haploinsufficiency of p53 is in itself likely to contribute to tumour progression in Taiwanese OSCCs.