p21/WAF1 expression as related to p53, cell proliferation and prognosis in epithelial ovarian cancer

• Published in: British Journal of Cancer Vol. 79; no. 11-12; pp. 1870 - 1878
• Main Authors: ANTTILA, M. A, KOSMA, V.-M, HONGXIU, J, PUOLAKKA, J, JUHOLA, M, SAARIKOSKI, S, SYRJÄNEN, K
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.04.1999
• Subjects: Biological and medical sciences; Carcinoma - genetics; Carcinoma - pathology; Cell Division - genetics; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - genetics; Female; Female genital diseases; Genes, p53; Genes, Tumor Suppressor; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Ki-67 Antigen - analysis; Medical sciences; Multivariate Analysis; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Prognosis; Regular; Tumors; Human; Cell proliferation; Antigen Ki 67; Carcinoma; Prognosis; Cell nucleus; Biological marker; Malignant tumor; Gene expression; Female genital diseases; Antigen; Ovarian diseases; Ovary; TP53 Gene; Genetics; Tumor suppressor gene
• ISSN: 0007-0920; 1476-5381; 1532-1827
• DOI: 10.1038/sj.bjc.6690298

The role and prognostic value of the tumour suppressor p21/WAF1 expression in epithelial ovarian cancer has not yet been defined. Therefore, the expression of p21/WAF1 was assessed immunohistochemically (IHC) in 316 epithelial ovarian malignancies in relation to p53, cell proliferation and patient survival. p21/WAF1 expression was inversely correlated with p53 and cell proliferation. Low p21/WAF1 expression was significantly associated with high grade of the tumour (P = 0.0005), advanced FIGO stage (P = 0.001) and primary residual tumour (P = 0.0001). Low p21/WAF1 expression was a marker of poor overall survival (P = 0.012). Similarly, p53-positivity and high cell proliferative activity were significant predictors of poor survival in univariate analyses. Moreover, the patients with p21-/p53+ tumours had a poorer overall (P < 0.00005) and recurrence-free (P = 0.0005) survival in univariate analyses, and the p21/p53 expression independently predicted tumour recurrence in Cox's multivariate analysis. Our results suggest that p21/WAF1 expression is mostly p53-dependent in epithelial ovarian cancer. High p21/WAF1 expression seems to function as a negative cell cycle regulator and as a marker of favourable disease outcome in epithelial ovarian cancer. In addition, the patients with their tumour expressing no or low p21/WAF1 protein but positive for p53 had a notably higher risk of recurrent disease, implicating that these patients might be more prone to treatment failures.