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

• Published in: British Journal of Cancer 1999-04, Vol.79 (11-12), p.1870-1878
• Main Authors: Anttila, M A, Kosma, V-M, Hongxiu, J, Puolakka, J, Juhola, M, Saarikoski, S, Syrjänen, K
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma - genetics; Carcinoma - pathology; Cell Division - genetics; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - genetics; Drug Resistance; Epidemiology; Female; Female genital diseases; Genes, p53; Genes, Tumor Suppressor; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Ki-67 Antigen - analysis; Medical sciences; Molecular Medicine; Multivariate Analysis; Oncology; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Prognosis; Regular; regular-article; Tumors
• ISSN: 0007-0920; 1476-5381; 1532-1827
• DOI: 10.1038/sj.bjc.6690298

Summary 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.