Assessment of vascular maturation in non-small cell lung cancer using a novel basement membrane component, LH39: Correlation with p53 and angiogenic factor expression

Angiogenesis, the formation of new vessels, has been demonstrated to be a p otent and independent indicator of prognosis in non-small cell lung cancer patients. The extent of differentiation of the tumor vessels may affect acc ess of peripheral white cells and egress or invasion of tumor cells. This h as not been assessed in relation to tumor microvessel density or other vari ables and may be a marker of vascular remodeling, LH39 is a monoclonal anti body recognizing an epitope located at the lamina lucida of mature small ve ins and capillaries but not in newly formed vessels. Rie examined the ratio of mature:immature vessels in 81 non-small cell lung carcinomas and correl ated the vascular maturation index (VMI) to different clinicopathological v ariables including angiogenesis, Mature vessels were defined by staining wi th. antibodies to both LH39 and to CD31, using double immunohistochemistry, whereas immature vessels stained only for CD31, VMI was defined as the per centage fraction of mature vessels (LH39 positive)/total number of vessels (CD31 positive). The median VMI in lung carcinomas was 46% (range, 15-90%), There was a significant inverse correlation between high VMI and low thymi dine phosphorylase expression (P = 0.0001), high VMI and nuclear p53 negati vity (P = 0.01), high VMI and low angiogenesis (P = 0.0001), as well as bet ween high VMI and absence of nodal involvement (P = 0.01). Low angiogenesis and high VMI were associated with a significantly better outcome (P = 0.00 01 and P = 0.02, respectively), These findings show that there is a wide va riation in the differentiation of tumor vasculature in lung carcinomas, and VMI gives new information on the degree of active tumor vascular remodelin g independently from microvessel quantitation.