Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer.

Abstract

Recent studies have drawn attention to intratumoral microvessel density (MVD) as a prognostic factor in invasive breast cancer. Various methods have been applied to assess MVD and the prognostic value of MVD in different studies varies considerably. Counting of microvessels in the most highly vascularized area (hot spot) of a tumour is the method most widely used. In this study we compared three counting methods. To assess MVD in 112 cases of invasive breast cancer with long-term follow-up we performed microvessel counting in the hot spot of the tumour in four and 10 fields of vision (HS-MVD4 and HS-MVD10) and microvessel counting in 10 fields of vision distributed systematically over the whole tumour area (global MVD). The HS-MVD4, HS-MVD10 and global MVD showed good correlations with each other. HS-MVD4 provided the highest number of microvessels (median value 71) followed by HS-MVD10 and global MVD, with median values of 58 and 39, respectively. HS-MVD4 showed the best prognostic value for overall survival (P = 0.0001) whereas HS-MVD10 showed less (P = 0.01) and the global MVD showed no (P = 0.75) prognostic value. In univariate analysis, the HS-MVD4 was the second strongest prognostic factor after tumour size. In multivariate survival analysis, the HS-MVD4, mitotic activity index (MAI), lymph node status and tumour size were found to be independent prognostic factors. When combining MVD4 and MAI in lymph node negative patients, none of the patients with low MVD (< 71/mm2) and a low MAI (< 10 per 10 HPF) died, in contrast to patients with a high MVD or high MAI who have a 10-year survival of 57%. These data suggest that the hot spot MVD in four fields of vision is a major independent prognostic factor for overall survival in invasive breast cancer. For the first time, it is shown that hot spot MVD provides additional prognostic information to well established factors like lymph node status and the MAI, and may therefore be useful for designing treatment strategies in invasive breast cancer.