Immunohistological Characterization of Actinic Keratoses with Varying Degrees of Proliferation

Background: Actinic keratoses (AKs) are considered early in situ forms of cutaneous squamous cell carcinoma (cSCC). However reliable histopathological or molecular markers for predicting the risk of progression are still lacking. The aim of this study was to investigate the relationship between immunohistochemical markers and basal proliferation patterns of AKs in order to identify histopathological associations that may be relevant for malignant transformation. Methods: A total of 97 AK samples from facial and scalp areas were retrospectively analyzed and classified according to their basal proliferation pattern (Pro I: non-proliferative and Pro III: proliferative). Immunohistochemical staining was performed for Ki-67, p53, p16 and podoplanin. In addition, histopathological parameters such as Röwert-Huber grade, inflammatory infiltrate, parakeratosis, elastosis and the presence of acantholysis were evaluated. Results: Pro III lesions were significantly more frequently associated with higher Röwert-Huber grades (AK III: 47.9% vs. 14.3%; p = 0.0004) and with acantholysis (p = 0.0004). No significant differences between the groups were found for Ki-67, p53 and p16. Podoplanin expression, however, was significantly higher in Pro III lesions (93.7% vs. 57.1%, p < 0.0001) and was predominantly localized basally. The combination of a PRO III pattern and podoplanin positivity identified a distinct histopathological subgroup associated with features linked to progression. Conclusions: Podoplanin expression, especially in combination with PRO III pattern and acantholysis, characterizes a histologically and biologically distinct AK subgroup. In contrast, Ki-67, p53 and p16 showed no additional discriminative value in this cohort. Podoplanin could therefore be a useful addition to existing classification systems and in the future support risk-adapted treatment decision. However, prospective longitudinal studies are required to determine its prognostic value.