Loss of Tumor Suppressor Gene Expression in High-Grade But Not Low-Grade Non-Hodgkin’s Lymphomas

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Abstract
The products of the MTS1/CDKN2 and retinoblastoma (RB) tumor suppressor genes, pl6 and pRB, act as agonists in controlling the late G1 cell cycle checkpoint. Inactivation of either gene occurs in a wide range of human malignant neoplasms. Data on the expression of both genes in the same set of malignant lymphoid neoplasms are scarce. We studied the pl6/pRB pathway in low-grade and high-grade non-Hodgkin’s lymphomas, using immunohistochemical techniques. Paraffin sections of 9 reactive lymph nodes and 43 low-grade and 60 high-grade malignant lymphomas were reacted with antibodies against pRB and pl6. All benign lymph nodes showed a normal pattern of RB and MTS1ICDKN2 expression. Of 101 evaluable lymphomas, only a single high-grade tumor displayed loss of RB reactivity. Loss of pl6 was identified in 14 of 55 evaluable high-grade lymphomas but not in any of the low-grade lesions. All but 3 of the RB- and pl6-negative cases were diffuse large cell lymphomas, for an abnormality rate of 55% in this category. While loss of RB function was a rare event in human lymphomagenesis, pl6 was absent in some 25% of high-grade non-Hodgkin’s lymphomas; diffuse large cell lymphomas were the primary target of tumor suppressor gene inactivation.

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