The results of methylation analysis, in combination with the results of our previous mutation analysis of CDKN2A locus and p53, revealed that 70% of SCCs have alterations in the RB1/p16 or p53 pathway.
Homozygous deletion of p16 appears to be common in esophageal squamous cell carcinomas but in adenocarcinomas, both gene deletion and transcriptional silencing of p16 were infrequent.
Reduced expression of the p16 protein was observed in 18 SCC (86%), while p16 gene alterations (hypermethylation (29%) and point mutation (33%)) were found in 11 (52%).
Both of CCNH-V270A C/C or C/T and XPD 751 A/A showed a significant longer survival in the squamous cell carcinoma subgroup (P=0.047 and P=0.034 respectively).
Most advanced squamous cell carcinomas (SCCs), however, are immortal, a phenotype that is associated with p53 and INK4A dysfunction, high levels of telomerase and loss of heterozygosity (LOH) at several genetic loci, suggestive of the dysfunction of other mortality genes.
Squamous cell carcinoma (SCC) immortality is associated with p53 and INK4A dysfunction, high levels of telomerase and loss of heterozygosity (LOH) of other chromosomes, including chromosome 4.
Squamous cell carcinoma arising in association with verruca vulgares and HPV-2: a clinicopathologic study with p16 and p53 immunohistochemical studies and human papillomavirus in situ hybridization studies.
Interestingly, inactivation of RASSF1A and p16 correlated well with an extended smoking habit (P=0.02), and exposure to asbestos (P=0.017) or squamous cell carcinoma (P=0.011), respectively.
CDKN2A mutation carriers presented more atypical naevi, multiple melanomas, and basal cell carcinoma, while non-carriers were more likely to have light-coloured hair, atypical naevi, and SCC.
This is the first description of specific abnormalities in tumor suppressor genes in RDEB associated SCC, and demonstrates that alterations in both p53 and p16ink4a can contribute to RDEB associated SCC.