EXPRESSION OF THE DOUBLE-STRANDED RNA-DEPENDENT PROTEIN-KINASE (P68) IN HUMAN BREAST TISSUES

P68 is a potent inhibitor of protein synthesis in virally infected cel ls and has been suggested to function in noninfected cells as a tumor suppressor gene. We have previously demonstrated that p68 expression c orrelates directly with cellular differentiation and inversely with pr oliferative activity in normal epithelium and in several human tumor s ystems. In order to determine the role of p68 in human breast cancer, we utilized immunohistochemistry and mapped the expression of p68 in t issue from 200 breast biopsy specimens. A total of 434 foci, ranging f rom normal breast tissue to infiltrating carcinoma were examined. We f ound that p68 was present at basal levels in normal lobular and lumina l ductal epithelial cells, with higher levels present in myoepithelial cells. Nonproliferative fibrocystic lesions showed variable expressio n of p68, with high levels seen within foci of apocrine metaplasia and low levels in cystically dilated terminal duct units. Low levels of p 68 were seen in typical ductal proliferations, lobular neoplasia (atyp ical lobular hyperplasia and lobular carcinoma in situ), and in fibroa denomas. Foci of atypical ductal hyperplasia in situ and invasive duct al carcinoma generally showed higher levels of p68 expression. Among t he infiltrating carcinomas, p68 expression correlated with nuclear gra de. This suggests that the ability of p68 to inhibit cellular prolifer ation may be impaired in breast cancer and that its expression, althou gh modestly Paralleling cellular differentiation, is not a predictive indicator of improved survival.