ANGIOGENESIS AS A PROGNOSTIC MARKER IN BREAST-CARCINOMA WITH CONVENTIONAL ADJUVANT CHEMOTHERAPY - A MULTIPARAMETRIC AND IMMUNOHISTOCHEMICALANALYSIS

It has now been clearly established that quantitative immunohistochemi cal methods applied to tumour angiogenesis under suitable quality cont rol conditions are a powerful prognostic tool for use in the initial a ssessment of breast carcinomas. Appropriate parameters for predicting the aggressiveness of tumours and their sensitivity to treatment are, however, still required. To determine whether the microvessel count (M VC) may serve to predict the chemotherapeutic response, a retrospectiv e study was carried out on a series of 162 patients with breast carcin oma, who were all treated with the same standard adjuvant chemotherapy . Angiogenesis was assessed by performing CD31 immunostaining and MVC per mm(2). Several other factors such as P53, ERBB2, BCL2, and Ki67 we re also measured, and their prognostic value was compared with that of the MVC. The MVC was not found to be correlated with any of the other prognostic parameters, but turned out to be of great prognostic value whatever the threshold value chosen, which suggests that it is contin uously, and at all levels. The median value of the MVC (43.5 per mm(2) ) divided this series into two significantly different prognostic cate gories, in terms of both disease-free survival (P=0.0002) and overall survival (P=0.037). Univariate analysis showed that most of the parame ters analysed were of prognostic value regarding the disease-free surv ival, namely grade (P=0.029), mitotic index (P=0.049), size (P=0.015), oestrogen receptors (P=0.022), progesterone receptors (P=0.018). P53 (P=0.0045), ERBB2 (P=0.046), and Ki67 (P=0.0008). As regards overall s urvival, grade and ERBB2 showed a loss of prognostic value. In multiva riate analysis on disease-free survival, the MVC was the most accurate prognostic factor (RR=2.64), followed by Ki67 (RR=2.06) and P53 (RR=1 .69). With respect to overall survival, the MVC ranked third among the prognostic parameters analysed. Standard chemotherapy did not reduce the high prognostic value of the MVC performed on tumour angiogenesis. This suggests that the MVC may predict the degree of resistance to ch emotherapy. Patients with high levels of angiogenesis, particularly no de-negative patients, might therefore be able to benefit from adjuvant therapy of another kind. (C) 1998 John Wiley & Sons, Ltd.