BCL-2 EXPRESSION IN LANGERHANS CELL HISTIOCYTOSIS

Langerhans' cell histiocytosis (LCH) is an abnormal accumulation of de ndritic histiocytes of unknown pathogenesis. It has recently been show n to be a clonal process. Bcl-2 is a proto-oncogene whose protein prod uct is known to inhibit apoptosis. The overexpression of bcl-2 has bee n demonstrated in a number of neoplasms, presumably prolonging the sur vival of the neoplastic cells. We examined the expression of bcl-2 in normal Langerhans' cells in the skin and in LCH by immunohistochemistr y for protein and in situ hybridization for mRNA to see if it could be implicated in the pathogenesis of this disorder Additionally, we perf ormed Southern analysis to determine if genomic rearrangement of the b cl-2 gene occurs in cases of LCH. Bcl-2 was not detected in normal ski n Langerhans' cells. Eleven of thirteen cases of LCH demonstrated bcl- 2 protein expression in the cytoplasm of the Langerhans' cells by immu nohistochemistry, while 12 of 13 cases had evidence of bcl-2 mRNA by i n situ hybridization. Southern analysis revealed a germline configurat ion of the bcl-2 gene in the five cases studied. These findings sugges t that bcl-2 expression is present and up-regulated in pathologic Lang erhans' cells, however, this overexpression does not appear to be due to genomic rearrangement.