The methodology of quantitation of microvessel density and prognostic value of neovascularization associated with long-term survival in Japanese patients with breast cancer

The present study updates results on methodology of quantitation of tumor n eovascularization and those on the prognostic value of microvessel density (MVD) in breast cancer tissue previously published in the World J. Surg. 21 : 49-56, 1997. The follow-up period of observation of the series was extend ed to 20 years, and new biological indicators (i.e., proliferating cell nuc lear antigen (PCNA), c-erbB-2, and p53) were included in the analysis. Ther e were 109 patients with primary breast cancer, from 1971 to 1979, followed up for a median of 14 years (range, 1-20). A representative median longitu dinal section of each breast tumor was immunohistochemically stained with f actor VIII-related antigen and analyzed. The three methods of identifying M VD were: (1) average microvessel count (AMC)/mm(2), (2) central microvessel count (CMC)/mm(2), and (3) highest microvessel count (HMC)/mm(2) Thirty-on e patients (28.4%) died of breast cancer. There was a relationship between MVD and peritumor blood vessel invasion (AMC: p = 0.0114, CMC: p = 0.0319, and HMC: p = 0.0009). However, there was no relationship between MVD and ot her factors. Univariate analysis showed that node status (p < 0.0001), hist ological grade (p < 0.0001), clinical tumor size (T) (p = 0.0002), PCNA (p = 0.0033), p53 (p = 0.0043), mitotic grade (p = 0.0092), AMC (p = 0.0214), and peritumor lymphatic vessel invasion (p = 0.0467) were significantly pre dictive of overall survival. HMC was borderline significant (p = 0.0702), w hile CMC and c-erbB-2 were not significant. Multivariate analysis showed th at T (p = 0.0005), node status (p = 0.0053), and AMC (p = 0.0485) were inde pendent factors, but neither CMC nor HMC was independent. AMC, a significan t independent prognostic factor, might be a better method than the others f or evaluating angiogenesis, but further and larger studies are warranted.