Intratumoral angiogenesis: a new prognostic indicator for stage I endometrial adenocarcinomas?
Giatromanolaki A., Sivridis E., Koukourakis MI., Georgoulias V., Gatter KC., Harris AL.
The prognostic significance of three recently emerged parameters, namely intratumoral angiogenesis and the antiapoptotic proteins bcl-2 and mutant p53, was investigated in a series of 124 patients with endometrial adenocarcinomas of the endometrioid cell type. All patients were treated with total abdominal hysterectomy and bilateral oophorectomy, without node dissection. When deep myometrial invasion or advanced stage of disease was confirmed, adjuvant radiotherapy was given. Intratumoral angiogenesis was assessed in tissue samples, after immunohistochemical staining, with the anti-CD31 monoclonal 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 endometrial adenocarcinomas, medium (15-30) in 33% of the tumors, and low (< 15) in the remaining cases (37%). A strong cytoplasmic and/or perinuclear expression of bcl-2 in more than 10% of the neoplastic cells was considered as being positive, and noted in 35.5% of the endometrial neoplasms; it was more frequent in the less vascularized carcinomas (P = 0.03). Nuclear p53 accumulation in an equal percentage of neoplastic cells (> 10%) was less common (7.2%). In univariate analysis, early stage of disease, absence of lymphatic-vascular 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 variable noted was stage of disease (P < 0.0001). Within stage I endometrial adenocarcinomas, only intratumoral angiogenesis was associated with prognosis (univariate analysis): high MVD cases had a significantly worse prognosis compared to medium MVD (P = 0.02). Low MVD adenocarcinomas, on the other hand, 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.