IMMUNODETECTION OF APOPTOSIS-REGULATING PROTEINS IN LYMPHOMAS FROM PATIENTS WITH AND WITHOUT HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

The expression of the apoptosis-regulating genes Bcl-2, Bcl-x, Bax, Mc l-1, and p53 was analyzed in 4 cases of human immunodeficiency, virus (HIV)-associated Hodgkin's disease, in 36 cases of HIV-related non-Hod gkin's lymphomas (NHLs), and in 109 cases of non-HIV-related NHLs by u sing immunohistochemistry. HIV-associated Hodgkin's disease samples we re positive for all markers. For the HIV-related NHL samples, 36, 66, 88, 100, and 94% of the cases were Bcl-2, Bcl-x, Bax, Mcl-1, and p53 p ositive, respectively. For the HIV-unrelated NHLs, Bcl-2, Bcl-x, Bax, Mcl-1, and p53 were found to be expressed in 69, 65, 82, 83, and 42%, respectively. No significant differences were observed in Bax and Mcl- 1 staining between HIV-related NHLs of B cell and T cell types. In con trast, Bcl-2 tons positive in 66/79 (83%) and 10/30 (33%) of B cell an d T cell HIV-related NHLs, respectively (P2 < 0.001). Peculiar pattern s were observed for hairy cell leukemia (Bax(+), Bcl-2(+), Mcl-1(-)) a nd for anaplastic large cell lymphoma (Bax(+), Mcl-1(+), Bcl-2(-)) in HIV-unrelated NHLs. Of interest, all cases with a positive expression of Bax were also found to express either Mcl-1 and/or Bcl-2, suggestin g that Mcl-1 and Bcl-2 may counteract the pro-apoptosis function of Ba r in vivo by protein-protein interaction within the tumor cell, as dem onstrated previously in vitro. These results suggest that apoptosis re gulation may have a role in the pathogenesis of some HIV-related and H IV-unrelated NHLs.