Nuclear localization of human AP endonuclease 1 (HAP1/Ref-1) associates with prognosis in early operable non-small cell lung cancer (NSCLC)

The present study examined the immunohistochemical expression of human AP e ndonuclease 1 (HAP1/Ref-1), the major endonuclease in the repair of apurini c/apyrimidinic (AP) sites in cellular DNA, in normal lung and lung carcinom as. Cellular expression of HAP1 was determined using a standard avidin-biot in-peroxidase complex (ABC) technique and an anti-HAP1 rabbit polyclonal an tibody on paraffin-embedded tissue sections from normal lung and in 103 pri mary non-small cell lung carcinomas (NSCLCs). In normal lung, the staining for HAP1 was found to be both nuclear and cytoplasmic in the pneumocytes of the alveoli. Superficial ciliated cells of the bronchial epithelium presen ted cytoplasmic staining, while staining for the basal cells was mostly nuc lear. Bronchial glandular cells demonstrated mixed nuclear and cytoplasmic staining. Long carcinomas showed all patterns of expression for HAP1. Loss of HAP1 expression was associated with low proliferation index (p=0.01) and with squamous histology (p=0.04). In squamous carcinomas, a significant co rrelation was observed between positive nuclear HAP1 and negative p53 expre ssion (p=0.03). A survival benefit was seen in patients presenting nuclear HAP1 expression and those presenting the nuclear HAP1+/p53- phenotype (p=0. 01 and 0.007, respectively). It is concluded that nuclear HAP1 localization may be relevant to its role as a DNA repair protein and/or to the recently proposed role as an activator of wild-type p53, and thus to the better out come seen in this group of patients. Copyright (C) 1999 John Wiley & Sons, Ltd.