Increased expression of TGF-beta/Smad proteins in basal cell carcinoma.

Background: Basal cell carcinoma (BCC) is the most common cancer in humans placing a significant burden on healthcare services worldwide. There is an increasing evidence that the development of cutaneous epithelial tumours is pathogenetically linked to dysregulations of the transforming growth factor beta (TGF-beta) and its signalling molecules, the Smads.

Objective: In the present study we aimed to investigate the mRNA as well as protein expression of TGF-beta/ Smad signalling proteins in patients with BCC and healthy controls.

Methods: In this prospective pilot study, 24 patients with BCC were recruited. Punch biopsies were harvested from the centre of the tumour (lesional) as well as an adjacent healthy skin site (non-lesional controls). In addition to the specimens of BCC patients, skin samples (healthy controls) were obtained from subjects who had no history of skin cancer (n = 25). Real-time RT-PCR as well as immunohistochemistry was performed. -

Results: The mRNA levels of TGF-b/Smad transducers observed in healthy controls did not significantly differ from TGF-beta/Smad levels observed in non-lesional skin of BCCs patients (P > 0.05). RT-PCR revealed significant mRNA overexpression of TGF-beta1, Smad3, and Smad7 in BCCs as compared to non-lesional skin (P < 0.05). TGF-beta1 mRNA expression significantly correlated with Smad3 (r = 0.60; P < 0.05) and Smad7 (r = 0.76; P < 0.05) levels. Immunohistochemistry demonstrated marked protein overexpression of Smad3 in tumour tissue as compared to non-lesional skin.

Conclusions: Our data suggest a possible role of TGF-beta/Smad signalling in the pathogenesis of BCC.