The epigenetic regulation of TP53 and CDKN2A is an attractive therapeutic target for the treatment of cSCC, as well as NOTCH activating agents capable to restore its tumour-suppressor function.
In response to miR-154 mimic or siRNA-WHSC1, SCC A431 and SCC-15 cell lines exhibited increased expression of P73, P16 and Bax, decreased expression of WHSC1, P53, c-myc and Bcl-2, as well as attenuated cell viability and enhanced cell apoptosis.
Sections of formalin fixed paraffin-embedded tumor tissue from 54 cases of Morbus Bowen (preinvasive cutaneous carcinoma) and 41 cases of invasive squamous cell carcinoma of the skin were subjected to HPV genotyping using Lipa (Line imuno probe assay), immunohistochemical staining for p16(INK4A), p53, pRb and prepared for flow cytometry DNA content analysis.
Next to sun exposure, the immunosuppressive regimen is an important risk factor for the development of SCC in OTRs.Various gene mutations (e.g.TP53) and genetic alterations (e.g. loss of CDKN2A, amplification of RAS) have been found in SCCs.
We investigated the expression of psoriasin, human beta-defensin-2, cathelicidin antimicrobial peptide/LL-37, e-cadherin, involucrin, p16(INK4a) , p53, cyclin D1 and microchromosome maintenance protein 7 in healthy skin and in lesions of psoriasis, CULP and SCC from the same patient. p16(INK4a) was overexpressed in CULP but not in the subsequent SCC.
The evaluation of a large number of AK specimens in this study have found a low gene mutation rate in low-graded AK lesions. p53 mutations rather than p16(INK4a) and/or Ha-ras mutations may be an early event in the development of AK to cutaneous SCC.
Promoter hypermethylation of the death-associated protein kinase and p16 genes does not appear to play an important role in the development of cutaneous squamous cell carcinoma.