APOPTOSIS-ASSOCIATED PROTEINS IN ORAL LYMPHOMAS FROM HIV-POSITIVE PATIENTS

Extranodal oral lymphomas, seen with increasing frequency in HIV infec tion, may have dysfunctional apoptotic mechanisms that favor tumor pro gression. The purpose of this study was to evaluate extranodal lymphom as from HIV-positive patients for expression of apoptosis-associated p roteins. Correlations were made with 10 histologically comparable extr anodal lymphomas from HIV-negative patients and 6 hyperplastic lymph n odes from otherwise healthy young adults. Formalin-fixed tissue sectio ns were immunohistochemically stained for apoptosis-associated protein s (Bcl-2, Bcl-x, Pax, Bak, p53, MDM2, BHRF). In situ hybridization was also done on deparaffinized sections for Epstein-Barr virus EBER mRNA . Eighteen consecutive oral lymphomas were studied in HIV/AIDS-positiv e patients. Four of 5 intermediate-grade lymphomas expressed Bcl-2 to a greater degree than did high-grade lymphomas (4 of 13). Most lymphom as were positive for Bcl-x and Pax, and few expressed Bak. The stainin g patterns for these proteins were similar to those seen in HIV-negati ve patients. Staining patterns were relatively consistent in the hyper plastic lymph nodes, whereas such patterns were irregular in lymphomas . Positive p53 staining was seen in 11 of 18 HIV-positive cases; 9 of these were also MDM2-positive. Double stains suggested that both p53 a nd MDM2 proteins were expressed in the same cells in these nine cases. Epstein-Barr virus-EBER mRNA was detected in 14 of 18 cases and in 3 of 10 cases from HIV-negative patients. BHRF staining was evident in o nly a few cells of three HIV-positive lymphomas. The irregular express ion of Bcl-2, Bcl-x, Bar, and Bak in oral lymphomas indicates dysfunct ional apoptotic mechanisms in these tumors. Bcl-2 staining differs wit h tumor grade. Positive staining for p53 and MDM2 proteins is a notabl e feature of lymphomas in HIV-positive patients and may relate to bind ing of MDM2 to wild-type p53. Epstein-Barr virus is more commonly asso ciated with oral lymphomas in HIV-positive patients, although the Epst ein-Barr virus-produced protein BHRF, which has Bcl-2-like activity, i s minimally expressed.