HUMAN AP ENDONUCLEASE-1 (HAP1) PROTEIN EXPRESSION IN BREAST-CANCER CORRELATES WITH LYMPH-NODE STATUS AND ANGIOGENESIS

Human AP endonuclease (HAP1) plays a major role in the repair of apuri nic/apyrimidinic (AP) sites in cellular DNA. We used immunohistochemis try to examine the expression of HAP1 in normal breast and in 102 prim ary breast carcinomas. In normal breast epithelium, HAP1 had a uniform ly nuclear localization. However, in lactating glandular epithelium, t he expression of HAP1 was predominantly cytoplasmic. In carcinomas, bo th nuclear and cytoplasmic (44%), cytoplasmic (28%) or nuclear stainin g (24%) were observed. In four cases (4%), no HAP1 expression was dete cted. All patterns of expression for HAP1 were demonstrated for ductal carcinomas in situ (DCIS), although comedo-type DCIS were usually acc ompanied by mostly cytoplasmic staining. Similarly, the HAP1 expressio n in regions of invasive tumour necrosis was cytoplasmic. Pure nuclear HAP1 expression was significantly correlated with low angiogenesis (P = 0.007) and negative lymph node status (P = 0.001). In contrast, cas es with cytoplasmic as well as nuclear staining were associated with p oor prognostic factors, such as high angiogenesis (P = 0.03) and node positivity (P = 0.03). The pure nuclear staining may be related to bet ter differentiation, as in normal breast, and hence better prognostic features, and cytoplasmic staining to a more metabolically active phen otype with high protein synthesis, as in lactating breast.