EXPRESSION OF BCL-2 PROTEIN AND KI-67 NUCLEAR PROLIFERATION ANTIGEN IN BENIGN AND MALIGNANT CUTANEOUS T-CELL INFILTRATES

The bcl-2 protein prolongs cell life by inhibiting apoptosis. Its expr ession has been studied in a variety of normal tissues and lymphomas b ut there is minimal information available concerning bcl-2 expression by benign and malignant cutaneous T-dells. Therefore, we investigated bcl-2 expression in a wide variety of cutaneous T-cell infiltrates usi ng one- and two-color immunohistologic techniques. bcl-2 was expressed by the majority of lesional CD3(+) T-cells in most cases. This includ ed 22/26 cases of mycosis fungoides (MF), 3/3 cases of non-MF cutaneou s T-cell lymphoma, 5/5 cases of lymphomatoid papulosis, 4/4 cases of T -cell rich cutaneous lymphoid hyperplasia, 2/3 cases of bullous pemphi goid, 2/2 cases of discoid lupus erythematosus and 1/1 case of lichen planus. Titration experiments and comparative studies of tonsil sectio n positive controls revealed that, relative to mantle zone B-cells, th ere was over- expression of bcl-2 by a variable subset of T-cells in m ost cases. Assessment of multiple biopsies in a subset of MF cases sho wed stable expression of bcl-2 over intervals of up to two years. In c ontrast to the widespread expression of bcl-2 in both early and advanc ed MF skin lesions, abundant expression of the nuclear proliferation a ntigen, Ki-67, was skewed toward advanced MF skin lesions. Ten percent or more Ki-67(+) cells were present in 5% of patients with patches/th in 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 bot h a polyclonal and multilineage phenomenon, suggesting that it occurre d by a physiologic rather than mutational mechanism. We conclude that bcl-2 expression is a common feature of cutaneous T-cell infiltrates t hat has minimal differential diagnostic value for distinguishing lymph omas from reactive T-cell infiltrates. In early MF lesions, abundant e xpression of bcl-2 and sparse expression of Ki-67 suggested that the a ccumulation of tumor cells during the initial progression of MF may be facilitated by prolonged clonal survival in conjunction with low-grad e clonal proliferation.