| Summary: | Background/Aims: Clinical and histological features of actinic keratosis (AK) cannot predict malignant transformation to invasive squamous cell carcinoma (iSCC) in individual lesions. We investigated whether patterns/distribution of T-cadherin in AK lesions have biomarker value in predicting transformation to iSCC. Methods: 28 specimens of cutaneous iSCC exhibiting adjacent or overlying AK were immunostained for T-cadherin and classified according to AK histological grade (AK I–III) and basal growth pattern (PRO I–III). Results: T-cadherin staining was absent/very weak in 16 and strongly positive in 12 cases. iSSCs lacking T-cadherin expression were most commonly (12/16 cases) associated with type AK I or PRO I lesions, whereas the majority (10/12 cases) of T-cadherin-positive iSCCs originated from AK II and AK III/PRO II and PRO III. In T-cadherin-negative iSCCs, T-cadherin expression was absent in overlying AK and early invasive tumour but retained in AK areas adjacent to the tumour. In contrast, T-cadherin-positive iSCCs displayed expression of T-cadherin in the adjacent AK and early invasive tumour. Conclusions: T-cadherin-negative iSCC arises from AK showing partial or extensive regional loss of T-cadherin in the basal layer of the epidermis. We speculate that T-cadherin loss in individual AK lesions could indicate potential transformation of AK into aggressive iSCC.
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