Detection of the apoptosis-suppressing oncoprotein bcl-2 in salivary gland lymphoma.

The bcl-2 proto-oncogene encodes an inner mitochondrial membrane protein that blocks apoptosis and programmed cell death in human lymphoid tissue. In this study a monospecific anti-human bcl-2 antibody that is reactive in formalin-fixed tissues was used with an avidin-biotin complex immunoperoxidase method to evaluate 41 cases of lymphoproliferative disorders of the salivary gland. The study cases were 26 primary salivary gland lymphomas (including 21 B-cell lymphomas, four T-cell lymphomas and one true histiocytic lymphoma) and 15 cases of myoepithelial sialadenitis. Bcl-2 expression is restricted to the mantle zone and interfollicular lymphocytes around reactive germinal centers of myoepithelial sialadenitis. Seventeen of the 21 B-cell lymphomas were positive for bcl-2, and were composed of mucosa-associated lymphoid tissue (MALT), centrocytic, centroblastic-centrocytic and centroblastic lymphomas. Noticeably, all 11 cases of MALT lymphoma were bcl-2 positive. In contrast, staining for bcl-2 was present in only one of four cases of T-cell lymphomas and was negative in one true histiocytic lymphoma. The expression of bcl-2 protein was also investigated in the ductal systems and epimyoepithelial islands of salivary glands from patients with malignant lymphoma and myoepithelial sialadenitis. While salivary ducts in eight of 15 cases of myoepithelial sialadenitis immunostained for bcl-2, epimyoepithelial islands showed bcl-2 expression in only five cases of myoepithelial sialadenitis. We found that ductal cells in the salivary gland from patients with primary non-Hodgkin's lymphomas expressed bcl-2 protein. It was of interest that epimyoepithelial islands in all cases of MALT lymphoma displayed bcl-2 expression, whereas other subtypes of B-cell lymphoma, T-cell lymphoma and true histiocytic lymphoma were invariably negative. These results indicate that bcl-2 is expressed in a wide variety of non-Hodgkin's lymphomas, especially when all 11 cases of MALT lymphoma are bcl-2 positive. Epimyoepithelial islands in MALT lymphoma express this oncoprotein, and their ability to induce bcl-2 synthesis resulted in the prevention of apoptosis and prolonged cell survival. Furthermore, the expression of bcl-2 protein in the lymphoma cells may be responsible for the induction of bcl-2 expression in the adjacent epimyoepithelial islands through a lymphocyte chemical mediator.