Angiogenesis, p53, and bcl-2 Expression as Prognostic Indicators in Endometrial Cancer

Abstract

We investigated the relation of expression of tumor-suppressor gene product p53, apoptosis-regulator gene product bcl-2, and CD34 (as a measure of microvessel density [MVD]) with traditional clinicopathologic prognostic variables in endometrial carcinoma (histologic type, grade, depth of myometrial invasion, angiolymphatic invasion, lymph node involvement). In specimens from 63 patients with endometrial carcinoma, the mean MVD (64.38+/-28.71 microvessels per 200x field) was not related to any clinicopathologic variables. Nuclear p53 expression was detected in 15 (23.8%) patients and was higher in nonendometrioid carcinomas (p<0.05) and in tumors with increasing histologic grade (p<0.001). Cytoplasmic bcl-2 staining was seen in 79.3% of the tumors. There was a negative correlation between bcl-2 expression and histologic type and tumor grade (p<0.05). In survival analysis, patient age, FIGO stage, high expression of p53, low expression of bcl-2, and high and intermediate MVD values were found to be the most significant prognostic indicators of survival (p<0.05). In multivariate regression analysis, FIGO stage and low bcl-2 expression were found to be the only independent indicators of prognosis (p<0.05).

Selected Immunohistochemical Prognostic Factors in Endometrial Cancer

“…A number of works confirm an association between elevated p53 expression and unfavorable prognostic factors in women with primary endometrial cancer. 12,13,20,32 Mariani et al 17 described p53 as the only molecular marker able to predict distant metastases independent of other histopathological, molecular, and cytokinetic parameters. Furthermore, various authors confirm a much higher p53 expression in serous tumors and clear cell tumors than in endometrial cancer, which support the hypothesis on the mutation of gene p53 as a late event in endometrial cancer and, on the contrary, an early event during the development of rare endometrial tumors.…”

P53/MDM2 overexpression in metastatic endometrial cancer: correlation with clinicopathological features and patient outcome

“…Several studies corroborate the relationship between P53 overexpression and unfavourable prognosis in women affected by primary EC [34][35][36][37][38][39][40][41]. Moreover, Geisler et al [42] reported that P53 immunoreactivity can be used to predict recurrence in patients affected by EC.…”

Expression of vascular endothelial growth factor and assessment of microvascular density with CD 34 and endoglin in proliferative endometrium, endometrial hyperplasia, and endometrial carcinoma

“…It has previously been suggested that endoglin was preferentially bound to endothelial cells in tissues participating in angiogenesis (12) . Although there is considerable evidence to suggest that MVD, as a parameter of angiogenic activity, has prognostic significance in many human malignancies, including genital tumors, for predicting metastasis and survival (2)(3)(4) , there are conflicting data demonstrating an association between tumor aggressiveness and MVD assessed by pan-endothelial markers in EC (4,(27)(28)(29) . For that reason, our preliminary data suggest that MVD count with endoglin expression seemed to reflect neoplastic angio-genesis better than CD 34 in endometrium.…”