c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-lot dependent

c-erbB-2-positive breast carcinomas are highly aggressive tumors. In vitro data on breast cell lines showed that c-erbB-2 enhanced translational efficiency of hypoxia inducible factor-lalpha (HIFlalpha) production (Laughner et aL, Mol Cell Biol 2001;21:3995-4005). We investigated the clinical correlate of this observation to assess whether c-erbB-2 expression was related to HIFlalpha expression, angiogenesis, and prognosis. A series of 180 breast carcinomas of known cerbB-2 status (90 c-erbB-2-positive and 90 c-erbB-2-negative carcinomas) were stained inummohistochemically for HIFlalpha and CD31 enclothelial cell antigen. c-erbB-2 positivity was clearly related to HIFlalpha protein expression and high angiogenesis. However, prognosis was decreased only In cases with simultaneous c-erbB-2 and HIFlalpha expression. If activation of c-erbB-2 in humans results in overexpression of HIFlalpha independently of conditions of hypoxia, as occur in experimental studies, this interaction may represent a main pathway conferring clinical aggressiveness to c-erbB-2positive breast tumors.