Inflammation is associated with progression of actinic keratoses to squamous cell carcinomas in humans

Background Squamous cell carcinoma (SCC) is a common skin tumour that may metastasize and lead to death. We have observed that before actinic keratoses (AK) progress to SCCs they may become tender and inflamed. In some of these, histological examination shows that they are, in fact, SCCs. Objectives To study the progression of AK to SCCs. Methods We studied skin tumours from 50 patients with either asymptomatic AK, inflamed AK or SCCs, using immunocytochemistry. The diagnosis of each tumour was confirmed by histological examination. Results Studies of differentiation using heat shock protein 27 showed a stepwise loss of differentiation as the tumours progressed from asymptomatic AK, through inflamed AK to SCCs. During the inflamed AK phase, there was a marked increase in T lymphocytes and Langerhans cells: the number of infiltrating cells diminished as progression to SCC occurred. There was an increase in immunoreactive p53 and the apoptosis inhibitor bcl-2 as tumours progressed from AK to SCCs, and a decrease in Fas and Fas ligand. Conclusions These studies have shown that progression from benign to malignant tumours may be associated with an inflammatory response, which appears to drive malignant conversion, but subsides rapidly following this conversion.