Prognostic significance of angiogenesis and Ki-67, p53, and p21 expression: A population-based endometrial carcinoma study

Purpose: For endometrial carcinoma patients, there is a need for improved i dentification of high-risk groups that may benefit from postoperative adjuv ant therapy. We therefore studied the prognostic impact of markers for cell proliferation, cell-cycle regulation, and angiogenesis among endometrial c arcinoma patients in a population-based setting. Patients and Methods: All patients diagnosed with endometrial carcinoma bet ween 1981 and 1985 in Hordaland County, Norway, were studied. The median fo llow up for the survivors was 11.5 years (range, 8 to 15 years), with no pa tient lost because of insufficient follow-up information. Paraffin-embedded tumor tissue, available in 96% of the cases (n = 142), was studied immunoh istochemically for microvessel density (MVD) and expression of Ki-67, p53, and p21 proteins. We used the hot spat method for calculation of MVD, and e xpression of Ki-67 and p21 protein, because this approach may increase the probability of detecting small aggressive clones of possible prognostic rel evance. The importance of these tumor markers was investigated in univariat e survival analyses and Cox regression analysis. Results: The majority of traditional clinicopathologic variables was signif icantly associated with the tumor biomarkers. Age, International Federation of Gynecology and Obstetrics (FIGO) stage, histologic type, histologic gra de, MVD, as well as Ki-67, p53, and p21 protein expression, all significant ly influenced survival in univariate analyses (P less than or equal to.05). In the Cox regression analysis, age, FIGO stage, MVD, Ki-67 expression, an d p53 expression were the only variables with independent prognostic impact (P less than or equal to.05), whereas histologic type, histologic grade, a nd p21 expression had no independent influence. A group of high-risk patien ts with more than one unfavorable marker was identified. Conclusion: In addition to age and FIGO stage, MVD, Ki-67, and p53 protein expression showed an independent prognostic impact. Thus, information deriv ed from routine histologic specimens identified a subgroup of high-risk end ometrial carcinoma patients in this population-based study J Clin Oncol 17: 1382-1390. (C) 1999 by American Society of Clinical Oncology.