HUMAN APURINIC ENDONUCLEASE-1 EXPRESSION IN A COLORECTAL ADENOMA-CARCINOMA SEQUENCE

Human apurinic endonuclease 1 (HAP1) plays a key role in the repair of baseless sites in DNA. HAP1 is also known to be a potent regulator of the binding activity of a number of transcription factors. We have ex amined the immunohistochemical expression of the HAP1 protein in norma l colorectal mucosa, hyperplastic polyps, tubulovillous adenomas, and carcinomas. In normal colonic mucosa, the predominant staining was nuc lear in the less differentiated cells located at the lower part of the crypt, but it was cytoplasmic in the more differentiated superficial colonic epithelium. HAP1 expression was nuclear in 3 of 30 adenomas (1 0%) and 5 of 44 carcinomas (11%), but it was cytoplasmic in 11 of 30 a denomas (37%) and 22 of 44 carcinomas (50%) and both nuclear and cytop lasmic in 16 of 30 adenomas (53%) and 17 of 44 carcinomas (39%). The o bserved staining in stromal fibroblasts and endothelial cells was nucl ear, whereas that in macrophages was cytoplasmic. Our data indicate th at HAP1 is expressed in different subcellular compartments during norm al differentiation and that this pattern is disrupted in adenomas and carcinomas. The differential localization may be relevant to the two d ifferent proposed functions of HAP1.