PROGNOSTIC VALUE OF INTRATUMORAL MICROVESSEL DENSITY, A MEASURE OF TUMOR ANGIOGENESIS, IN NODE-NEGATIVE BREAST-CARCINOMA - RESULTS OF A MULTIPARAMETRIC STUDY

In the present study we update previous results on the prognostic valu e of intratumoral microvessel density (IMD), determined immunocytochem ically using the monoclonal antibody CD-31 and a standard streptavidin -immunoperoxidase technique, published in the J Clin Oncol 12:454-466, 1994. This study was undertaken in those 211 node-negative breast can cer (NNBC) cases of that series of which we had pathological material available to determine all the prognostic indicators. The median perio d of follow-up has been extended to 78 and 80 months for relapse-free survival (RFS) and overall survival (OS), respectively, and new biolog ical indicators (i.e. Ki-67 labeling and 67 kDa laminin receptor expre ssion) were included in the analysis. The main results obtained are: i ) a confirmation that IMD is not associated with the other biological markers studied, i.e. expression of p53 protein, c-erbB-2 protein, 67 kDa laminin receptor, and cell kinetics; IMD was weakly associated onl y with histological grade (p = 0.053); ii) IMD remains a highly signif icant prognostic factor for RFS and OS (p < 0.0001 and p = 0.018, resp ectively) in univariate analysis; iii) in multivariate analysis on RFS , IMD (likelihood ratio test (LRT) = 30.16; p < 0.0001), 67 kDa lamini n receptor (LRT = 9.80; p = 0.0017), the IMD/67 kDa laminin receptor i nteraction (LRT = 8.62; p = 0.0033), tumor size (LRT = 8.56; p = 0.003 4), and p53 protein (LRT = 4.96; p = 0.025) are significant and indepe ndent prognostic indicators. For OS, only tumor size (LRT = 8.34; p = 0.0038), menopausal status (LRT = 5.16; p = 0.023), p53 protein (LRT = 4.37; p = 0.036), and IMD (LRT = 4.05; p = 0.044) retain a significan t and independent prognostic value. The results of this study confirm the prognostic importance on RFS of the variables previously tested, b ut not of peritumoral lymphatic vessel invasion. A novel finding is th at 67 kDa laminin receptor and the IMD/67 kDa laminin receptor interac tion are also significant and independent variables. For OS, the resul ts confirm that both IMD and tumor size are significant and independen t variables. With prolonged follow-up the novel finding that emerges i s the prognostic importance of menopausal status and p53 protein. This new information could be useful for a more accurate selection of high -risk NNBC patients who require careful follow-up and may benefit from adjuvant therapy.