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

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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.