Intratumoral angiogenesis: A new prognostic indicator for stage I endometrial adenocarcinomas?

The prognostic significance of three recently emerged parameters, namely in tratumoral angiogenesis and the antiapoptotic proteins bcl-2 and mutant p53 , was investigated in a series of 124 patients with endometrial adenocarcin omas of the endometrioid cell type. All patients were treated with total ab dominal hysterectomy and bilateral oophorectomy, without node dissection. W hen deep myometrial invasion or advanced stage of disease was confirmed, ad juvant radiotherapy was given. Intratumoral angiogenesis was assessed in ti ssue samples, after immunohistochemical staining, with the anti-CD31 monocl onal antibody. The mean microvessel density (MVD) was 23.2 +/- 14.1 (range 4-60; 95% CI 20-25.8). Microvessel density was high (>30) in 30% of endomet rial adenocarcinomas, medium (15-30) in 33% of the tumors, and low (<15) in the remaining cases (37%). A strong cytoplasmic and/or perinuclear express ion of bcl-2 in more than 10% of the neoplastic cells was considered as bei ng positive, and noted in 35.5% of the endometrial neoplasms; it was more f requent in the less vascularized carcinomas (P = 0.03). Nuclear p53 accumul ation in an equal percentage of neoplastic cells (>10%) was less common (7. 2%). In univariate analysis, early stage of disease, absence of lymphatic-v ascular space Invasion (LVI), and low intratumoral MVD were the parameters associated with an improved survival (P = 0.0001, P = 0.001, and P = 0.009, respectively). In multivariate analysis, however, the only independent var iable noted was stage of disease (P < 0.0001). Within stage I endometrial a denocarcinomas, only intratumoral angiogenesis was associated with prognosi s (univariate analysis): high MVD cases had a significantly worse prognosis compared to medium MVD (P = 0.02). Low MVD adenocarcinomas, on the other h and. were associated with an intermediate prognosis, indicating that other factors, such as hypoxia and related mechanisms, may also be important. It is suggested that intratumoral angiogenesis may prove useful in selecting a subgroup of cancer patients, among others with stage I endometrial disease . that would benefit from additional treatment.