Assessment of vascular maturation in lung and breast carcinomas using a novel basement membrane component, LH39.
Kakolyris S., Giatromanolaki A., Koukourakis M., Kaklamanis L., Kouroussis CH., Bozionelou V., Georgoulias V., Gatter KC., Harris AL.
LH39, is a monoclonal antibody recognizing an epitope located at the lamina lucida of mature small veins and capillaries but not in newly- formed vessels of several pathological conditions including cancer. We examined the ratio of mature/immature vessels in 50 breast and 81 lung carcinomas and correlated the vascular maturation index (VMI) to different clinicopathological variables including angiogenesis. Mature vessels were defined by staining with antibodies to both LH39 and CD31, using double immunohistochemistry, whereas immature vessels stained only for CD31. VMI was defined as the percentage fraction of mature vessels (LH39 positive)/total number of vessels (CD31 positive). VMI in breast carcinomas ranged from 0-47% (median 8.75%), which was significantly lower than that observed in the normal breast cases (range 54%-70%; median 68%). The median VMI in the non-small cell lung carcinomas was 46% (range 15%-90%). There was a significant inverse correlation between high tumor VMI and absence of nodal involvement in both breast and lung tumors examined (p=0.01). Thymidine phosphorylase (TP) expression, but not vascular endothelial growth factor (VEGF) expression, was related to a low VMI showing an intense vascular remodeling in TP expressing cases. Thus, assessment of vessel maturation might be complementary to microvessel number to aid the identification of patients who might benefit from specific antiangiogenic therapies or vascular targeting treatment.