Expression of bcl‐2 protein and Ki‐67 nuclear proliferation antigen in benign and malignant cutaneous T‐cell infiltrates

Abstract

The bcl‐2 protein prolongs cell life by inhibiting apoptosis. Its expression has been studied in a variety of normal tissues and lymphomas but there is minimal information available concerning bcl‐2 expression by benign and malignant cutaneous T‐cells. Therefore, we investigated bcl‐2 expression in a wide variety of cutaneous T‐cell infiltrates using one‐ and two‐color immunohistologic techniques, bcl‐2 was expressed by the majority of lesional CD3 + T‐cells in most cases. This included 22Departments of 26 cases of mycosis fungoides (MF), 3/3 cases of non‐MF cutaneous T‐cell lymphoma, 5/5 cases of lymphomatoid papulosis, 4/4 cases of T‐cell rich cutaneous lymphoid hyperplasia, 2/3 cases of bullous pemphigoid, 2/2 cases of discoid lupus erythematosus and 1/1 case of lichen planus. Titration experiments and comparative studies of tonsil section positive controls revealed that, relative to mantle zone B‐cells, there was over‐ expression of bcl‐2 by a variable subset of T‐cells in most cases. Assessment of multiple biopsies in a subset of MF cases showed stable expression of bcl‐2 over intervals of up to two years. In contrast to the widespread expression of bcl‐2 in both early and advanced MF skin lesions, abundant expression of the nuclear proliferation antigen, Ki‐67, was skewed toward advanced MF skin lesions. Ten percnt or more Ki‐67 + cells were present in 5% of patients with patches/thin plaques, 38% with moderate plaques, 64% with thick plaques and 100% with tumor nodules. Two‐color immunohistologic analysis combined with molecular biologic analysis of clonality in the cases of T‐cell rich cutaneous lymphoid hyperplasia indicated that bcl‐2 expression was both a polyclonal and multi‐lineage phenomenon, suggesting that it occurred by a physiologic rather than mutational mechanism. We conclude that bcl‐2 expression is a common feature of cutaneous T‐cell infiltrates that has minimal differential diagnostic value for distinguishing lymphomas from reactive T‐cell infiltrates. In early MF lesions, abundant expression of bcl‐2 and sparse expression of Ki‐67 suggested that the accumulation of tumor cells during the initial progression of MF may be facilitated by prolonged clonal survival in conjunction with low‐grade clonal proliferation.