Thus, these ancillary techniques, particularly p16 immunohistochemistry, are useful for distinguishing vulvar BCCs from basaloid forms of high-risk HPV-related vulvar SCC.
A statistically significant (p = 0,012) increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%); in particular in HPV positive samples over-expressing p16INK4a.
A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 x 10(-9)), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 x 10(-10)).
By analysing various microdissected areas of basal cell carcinoma using real-time quantitative PCR we observed upregulation of p16 mRNA in invasive tumour cells compared to centrally localized tumour cells.
A role for p16(INK4a) in basal cell carcinoma is suggested by the observation that p16(INK4a) was upregulated at the invasive front of the majority of basal cell carcinomas with infiltrative growth patterns, accompanied by cessation of proliferation.
Since it has been reported that BCC retain wild-type p16(INK4A) and here BCC with CpG-methylation of 14-3-3sigma did not show CpG-methylation of p16(INK4A) (0/17), silencing of 14-3-3sigma may contribute to evasion of senescence in BCC.
These data indicate that the presence of MPM is associated with a modest incidence of a family history of melanoma, DN, or BCC and a small association with CDKN2A mutations.
Three different somatic mutations that all harbor the signature of ultraviolet light (two of p16INK4A and one of p53) were also detected in the basal cell carcinoma.
Our results provide evidence of a significantly high occurrence of loss of heterozygosity for the 9p21-p22 locus; however, lack of p16INK4a/p19ARF mutation suggests that these genes seem not to be implicated by mutational inactivation in the development of basal cell carcinoma.