Relationship of vascular maturation in breast cancer blood vessels to vascular density and metastasis, assessed by expression of a novel basement membrane component, LH39

Angiogenesis, the formation of new vessels, has been demonstrated to be an indicator of prognosis in breast cancer patients. The extent of differentia tion of the tumour vessels may affect access of peripheral white cells and egress or invasion of tumour cells. This has not been assessed in relation to tumour microvessel density or other variables and may be a marker of vas cular remodelling. LH39 is a monoclonal antibody recognizing an epitope loc ated at the lamina lucida of mature small veins and capillaries but not in newly formed vessels. To study vascular differentiation in breast tumours, we examined the vascular maturation index (VMI) in 12 normal and 50 breast carcinomas and this was correlated with different clinicopathological varia bles including angiogenesis. Mature vessels were defined by staining with a ntibodies to both LH39 and to CD31, using double immunohistochemistry, wher eas immature vessels stained only for CD31. VMI was defined as the % fracti on of mature vessels (LH39-positive) / total number of vessels (CD31-positi ve). The VMI was significantly higher in normal (54-68.5%; median 66.5%) th an in tumours (0-47%; median 8.8%) (P = 0.0005), There was a significant in verse correlation between the tumour VMI and nodal status (Fishers exact te st, P = 0.01) and between high VMI and low thymidine phosphorylase (TP) exp ression (Mann-Whitney U-test, P = 0.01). No significant association between VMI and tumour size, oestrogen receptor, epidermal growth factor receptor, grade, angiogenesis, patient age, or E-selectin was seen. There was a sign ificant reduction in relapse-free survival (P = 0.01) with high angiogenesi s. These findings show that the VMI gives new information on the mechanism of tumour angiogenesis independently from microvessel quantitation, there i s a wide variation in the differentiation of tumour vasculature but the deg ree of capillary differentiation is not associated with quantitative angiog enesis. The VMI identifies a subset of patients who have a high chance of r egional node involvement. (C) 2000 Cancer Research Campaign.