Immunocytochemical detection of cyclin, a proliferation-associated protein, in cytologic preparations

Cyclin is a nuclear protein associated with DNA-polymerase delta, whose expression correlates with cell proliferation in vitro. To assess the value of cyclin staining in diagnostic cytology, an anticyclin monoclonal antibody was used to survey cyclin expression in cytologic preparations obtained as "bench top" aspirates from surgically resected specimens. The tissues assayed included carcinomas and normal and benign proliferative tissues of renal, mammary, prostatic and colonic origin. Staining was performed via the avidin-biotin-complex immunoperoxidase method. The staining of tumor cells was nuclear, with sparing of the nucleoli; the results were variable in different areas of a given tumor and varied significantly between tumors of the same histopathologic type. Benign proliferative tissues also showed staining. Nonproliferative tissues, such as renal tubules adjacent to a renal cell adenocarcinoma, were largely, but not entirely, nonstaining. The percentage of cyclin-positive nuclei was sometimes much higher than the typical percentages of tumor cells found in S phase. This observation was confirmed in two cases in which cyclin staining was much greater than the percentage of S-phase cells detected by flow cytometry. This suggests either stabilization of the protein beyond S phase in cells and/or dysregulation of cyclin expression in malignant cells. The viability of unfixed surgically resected tissue may also have affected the detection of cyclin, a problem that should not exist with clinically aspirated tissue fixed immediately after aspiration. These preliminary observations suggest that the selective use of cyclin staining may facilitate cytologic diagnoses. Furthermore, the wide range of cyclin expression within tumors of one histologic type suggests that cyclin expression may serve as a new parameter for investigating tumor behavior and prognosis.