Possible associations among expression of p14ARF, p16INK4a, p21WAF1/CIP1, p27KIP1, and p53 accumulation and the balance of apoptosis and cell proliferation in ovarian carcinomas

Abstract

BACKGROUND. Although there are several reports of changes in expression of cyclin-dependent kinase inhibitors in ovarian carcinomas, little is known about their associations with tissue kinetics in the various histologic subtypes. METHODS. In total, 131 carcinomas were immunohistochemically investigated for expression of p14ARF (p14), p16INK4a (p16), p21WAF1/Cip1 (p21), and p27Kip1 (p27). The results also were compared with data for apoptosis, cell proliferation, p53 status, and survival. Western blot and mRNA analyses were conducted on 35 malignant ovarian tumor samples. RESULTS. Significant differences in tissue kinetics determined by ratios of apoptotic relative to mitotic indices were observed among histologic subtypes of ovarian carcinomas, showing a shift toward predominance of cell proliferation in serous and cell deletion in clear cell types. The expression of p16, p21, p27, and p53 was associated closely with changes in cell proliferation rather than apoptosis and survival, dependent on the subtype. Positivity for p16 and p21 in the Western blot assay was significantly related to the results for immunohistochemical but not mRNA analyses, indicating possible posttranscriptional regulation of these genes. CONCLUSIONS. The findings indicate that the several cyclin-dependent kinase inhibitors investigated are expressed differently among histologic subtypes of ovarian carcinomas, associated with differences in tissue kinetics and the balance of apoptosis and cell proliferation. © 2001 American Cancer Society.