Possible associations among expression of p14(ARF), p16(INK4a), p21(WAF1/CIP1), p27(KIP1), and p53 accumulation and the balance of apoptosis and cellproliferation in ovarian carcinomas

BACKGROUND. Although there are several reports of changes in expression of cyclin-dependent kinase inhibitors in ovarian carcinomas, little is known a bout their associations with tissue kinetics in the various histologic subt ypes. METHODS. In total, 131 carcinomas were immunohistochemically investigated f or expression of p14(ARF) (p14), p16(INK4a) (p16), p21(WAF1/Cipl) (p21), an d p27(Kipl) (p27). The results also were compared with data for apoptosis, cell proliferation, p53 status, and survival. Western blot and mRNA analyse s 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 subty pes of ovarian carcinomas, showing a shift toward predominance of cell prol iferation in serous and cell deletion in clear cell types. The expression o f p16, p21, p27, and p53 was associated closely with changes in cell prolif eration rather than apoptosis and survival, dependent on the subtype. Posit ivity for p16 and p21 in the Western blot assay was significantly related t o the results for immunohistochemical but not mRNA analyses, indicating pos sible posttranscriptional regulation of these genes. CONCLUSIONS. The findings indicate that the several cyclin-dependent kinase inhibitors investigated are expressed differently among histologic subtype s of ovarian carcinomas, associated with differences in tissue kinetics and the balance of apoptosis and cell proliferation. (C) 2001 American Cancer Society.