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

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.

Behavior of cervical intraepithelial neoplasia (CIN) associated with various human papillomavirus (HPV) types.

201 cervical punch biopsies which showed CIN lesions and were obtained between 1967 to 1977 from Falu Hospital patients, with long-term follow-up data were examined histologically and by DNA typing for human papillomavirus (HPV). We used in situ hybridization for HPV types 6, 11, 16, 18, 31 and 33 and related our findings to the behaviour of the lesion (103 regressed spontaneously and 98 progressed, some of them to invasive cervical carcinoma). There was evidence of HPV infection in 75.6% (152/201) of these lesions on histological examination, and in 53.2% (107/201) on in situ DNA hybridization. Lesions positive for HPV by both methods occurred in the younger age group (Pearson's correlation coefficient, P = 0.008). HPV 16 was found in 51/152 (33.6%) of the HPV lesions, HPV in 12.5%, and HPV 33 in 8.5% HPV 16 was highly significantly (P = 0.0001), and HPV 18 and HPV 33 were significantly (P = 0.008 and P = 0.007, respectively) associated with increasing grades of CIN. Progression to invasive carcinoma was directly (and regression inversely) correlated with the severity of CIN in the first biopsy (P = 0.005). Almost 74% (17/23) of the HPV-CIN III lesions progressed, while only 25% of the HPV-NCIN lesions (6/24) did so. The progression rate was 84.6% for HPV 33 lesions and 52.9% for HPV 16. On the other hand, progression was less common with HPV 6 (25%), and HPV 31 (30.0%). Histological grade and HPV type appear to be of value as prognostic indices.