Proapoptotic and antiapoptotic markers in cutaneous T-cell lymphoma skin infiltrates and lymphomatoid papulosis

Background In cutaneous T‐cell lymphoma (CTCL) lesions, both reactive T cells and malignant T cells intermingle. The disease progression is mostly slow. Recent evidence suggests that even if clinical remission is reached, malignant cells persist and a relapse follows sooner or later. To what extent tumour cell apoptosis occurs in the skin lesions either due to the reactive T cells or to therapeutic efforts is not known. Objectives To determine the extent of tumour cell apoptosis and the expression of proapoptotic and antiapoptotic markers in serial skin lesion samples from patients with CTCL, and to compare the findings with those in patients with lymphomatoid papulosis (LyP). Methods Thirty‐four skin samples were obtained from 12 patients with CTCL at the time of diagnosis and at a mean of 1·6, 3 and 6 years later. The patients received psoralen plus ultraviolet A (PUVA), electron beam or cytostatic treatments. In addition, fresh post‐treatment samples from three patients with CTCL undergoing PUVA therapy were obtained. For comparison, skin biopsies of five patients with LyP were studied. Immunohistochemical demonstration of the expression of the following markers was performed on formalin‐fixed skin sections: Fas (CD95), Fas ligand (FasL), bcl‐2, granzyme B, the tumour‐suppressor protein PTEN and the effector caspase, caspase‐3. The malignant cells were identified morphologically, and apoptotic cells were identified with the terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labelling method on parallel sections. Results In untreated CTCL lesions, apoptotic lymphocytes were extremely rare, and no increase in the number of apoptotic cells was observed after any of the treatments used. In LyP, apoptotic cells were more frequent, comprising on average 5% of the infiltrate. The apoptosis‐associated markers Fas, FasL, caspase‐3 and granzyme B were expressed by morphologically neoplastic cells in CTCL and by large atypical cells in LyP, with no significant differences. However, only a few reactive cells in CTCL infiltrates expressed granzyme B while about 10% of the corresponding cells were positive in LyP. The expression of antiapoptotic bcl‐2 was more frequent in CTCL than in LyP, while PTEN expression was high in both instances. The number of bcl‐2+ cells tended to decrease after therapy. When comparing the findings between the first and the last samples, a decrease in the number of bcl‐2+ cells and an increase in Fas+ cells w