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Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent tumors in the Caucasian population. The formation of these tumors is a consequence of long term UV-exposure of the skin. UV-light induces DNA damage in cells. If the damaged DNA cannot be repaired or the DNA damaged cell is not eliminated by apoptosis (so-called sunburn cells), cell transformation and tumor development can be the outcome. Fas-ligand (FasL), a member of the tumor necrosis superfamily, is a key molecule involved in the elimination of sunburn cells. FasL is expressed in normal skin epidermis, preferentially in the basal layer. Regulation of FasL expression has a dual effect on cancerogenesis. On the one hand, FasL expression is down regulated in skin epidermis by UV irradiation leading to the loss of its sensor function and thereby increasing the risk of cell transformation and skin tumor development. On the other hand, once BCC or SCC have developed, FasL is strongly up-regulated. High expression of FasL may now serve to protect the tumor from the attack of immune effector cells. To prove the immune escape hypothesis in vivo, the prevention or downregulation of FasL expression in tumor tissue is required. Two approaches were successfully applied to silence the FasL gene in BCC tissues ex vivo, the antisense technology and RNA interference with small interfering RNA duplexes. With both techniques FasL expression can be efficiently downregulated in BCC tissues pathing the way to test the immune escape hypothesis in vivo.

Beside UV exposure and other exogenous and endogenous factors, the activation of telomerase plays an important role in the cancerogenesis of both skin tumors. Model studies indicate that telomerase activation occurs early in the cancerogenesis of the skin. Telomerase activity (TA) has also been found in the proliferating basal cells of normal, predominantly of sun-exposed skin. Studies have demonstrated its presence in 167 of 186 (90%) basal cell carcinomas (BCC) and in 58 of 75 (77%) squamous cell skin carcinomas (SCC). While the potential for malignancy is higher in SCC, telomerase activation is more frequent in BCC. The period without recurrence is no shorter in patients with telomerase activity in a tumor than it is in patients without telomerase activity in the tumor. Proof of telomerase cannot be used as a prognostic marker in these tumors. However, it is important to prove telomerase activity in tumor-free marginal tissue, and this has a different impact on each of the tumor types. Telomerase activation originating in a BCC tumor-free margin would indicate field cancerization in the surrounding tissue. It could be used as a prognostic marker because the interval without recurrence in patients with TA positive BCC marginal tissue is significantly shorter than that in patients with a TA negative BCC margin. In contrast, telomerase activation in skin and in oral SCC tumor-free margins is associated with a significantly prolonged interval with no recurrence. The telomerase activation in this case can more probably be interpreted as an immune signal and lymphocytic defense function in the tumor margin, which can be confirmed by an in-situ demonstration of telomerase in the tumor margin tissue. The findings in histopathologically tumor-free margin tissue must be supported in further studies with a larger patient population.