We searched for p16, Cdk4 and p53 gene mutations in 20 squamous cell carcinomas (SSCs), 1 actinic keratosis (AK), and 28 basal cell carcinomas (BCCs), using PCR-SSCP.
Microdissection-based studies have also shown that different parts of individual BCC tumors can share a common p53 mutation yet differ with respect to additional alterations within the p53 gene, consistent with subclonal development within tumors.
Therefore, we suggest that a putative tumor suppressor gene on the region of 9q, but not p53 gene, plays a critical role in the pathogenesis of BCC, independent of race.
The results from cutaneous XP tumors, including 27 squamous cell carcinomas and 6 basal cell carcinomas, show a very high level (86%) of p53 mutations.
These results suggest that (i) the major initiator of p53 mutations in basal cell carcinoma in psoralen and ultraviolet A-treated psoriasis patients is environmental and/or therapeutic ultraviolet(B) exposure, and that (ii) psoralen and ultraviolet A itself causes only a smaller portion of p53 mutations in psoralen and ultraviolet A-associated basal cell carcinomas.
Studies on basal cell carcinoma (BCC) have demonstrated that patched gene and p53 gene located at 9q22.3 and 17p13 are the main genes responsible for the onset of this tumor.
This spontaneous apoptosis decreases with increasing bcl-2 (in basal cell carcinoma), whereas it does not appear to be related to p53 level expression.
Mutations of the p53 gene were detected in seven of 23 SCCs (30%), three of 25 BCCs (12%), and none in all cases of Bowen's disease, solar keratosis, or keratoacanthoma.
In the 22 non-aggressive tumors, less than 50% of cells showed positive staining. p53 immunoreactivity was significantly higher in aggressive BCCs than non-aggressive ones (x(2) test; p < 0.01).
These results suggest that the mutation in the p53 gene plays a significant role in the tumorigenesis of BCC developed in less-exposed areas as well as those in sun-exposed areas in Japanese patients.
In this work, we have evaluated resistance mechanisms to MAL-PDT developed by three BCC cell lines (ASZ, BSZ and CSZ), derived from mice on a ptch+/- background and with or without p53 expression, subjected to 10 cycles of PDT (10<sup>th</sup>G).
A correlation was observed between p53 expression and the proliferative activity of differentiated squamous cell carcinomas (P < 0.066), undifferentiated squamous cell carcinomas (P < 0.05) and basal cell carcinomas (P < 0.01).
Our results indicate that UV radiation is responsible for the induction of p53 mutations and perhaps for the initiation of both aggressive and nonaggressive BCCs and SCCs.
Microdissection of small parts (50-100 cells) of individual tumors showed BCC to be composed of a dominant cell clone and prone to genetic progression with appearance of subclones with a second and even third p53 mutation.
The aim of the present work is to test association between POMC and TP53 genetic variability, the possible interplay with host factors and the risk of basal cell carcinoma of skin.
Taken together, our data suggest that functional interactions between KIR and HLA modify risks of BCC and SCC and that KIR encoded by the B genes provides selective pressure for altered p53 in BCC tumors.
With two different anti-p53 antibodies of CM1 and DO7, p53 expression was frequently detected in the epidermis adjacent to BCCs arising on the face and in the normal epidermis with usual sun exposure.