Evaluation of T lymphocyte subpopulations in Actinic Keratosis, In Situ and Invasive Squamous Cell Carcinoma of the Skin

Abstract

Background

Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing two semi-quantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions.

Methods

Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semi-quantitative Klintrup-Mäkinen score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification.

Results

An increase of all TIL subpolulations from precursor lesions towards inSCC was shown by both scoring systems. Treg counts progressively increased from normal skin to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes.

Conclusions

T-cells and cytotoxic T-cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K-M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC.