This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kakolyris, S. Articles by Harris, A. L. Search for Related Content PubMed PubMed Citation Articles by Kakolyris, S. Articles by Harris, A. L.

Assessment of Vascular Maturation in Non-Small Cell Lung Cancer Using a Novel Basement Membrane Component, LH39

Correlation with p53 and Angiogenic Factor Expression

Tumor and Angiogenesis Research Group, Departments of Clinical Oncology and Radiotherapy [S. K., M. K., V. G.] and Pathology [P. K.], University Hospital of Heraklion, 71110 Crete, Greece; Histopathology Department, Democritus University, Alexandroupolis, 80100 Thrace, Greece [A. G., E. S.]; Experimental Dermatology Laboratory, The Royal London Hospital, London E1 1BB, United Kingdom [I. M. L.]; and Department of Cellular Science [K. C. G.], ICRF Molecular Oncology Laboratory [A. L. H.], John Radcliffe Hospital, University of Oxford, OX3 9DU, United Kingdom

Angiogenesis, the formation of new vessels, has been demonstrated to be a potent and independent indicator of prognosis in non-small cell lung cancer patients. The extent of differentiation of the tumor vessels may affect access of peripheral white cells and egress or invasion of tumor cells. This has not been assessed in relation to tumor microvessel density or other variables and may be a marker of vascular remodeling. 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. We examined the ratio of mature:immature vessels in 81 non-small cell 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 to 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). The median VMI in lung carcinomas was 46% (range, 15–90%). There was a significant inverse correlation between high VMI and low thymidine phosphorylase expression (P = 0.0001), high VMI and nuclear p53 negativity (P = 0.01), high VMI and low angiogenesis (P = 0.0001), as well as between high VMI and absence of nodal involvement (P = 0.01). Low angiogenesis and high VMI were associated with a significantly better outcome (P = 0.0001 and P = 0.02, respectively). These findings show that there is a wide variation in the differentiation of tumor vasculature in lung carcinomas, and VMI gives new information on the degree of active tumor vascular remodeling independently from microvessel quantitation.

This article has been cited by other articles:

				A. Bhattacharya, M. Seshadri, S. D. Oven, K. Toth, M. M. Vaughan, and Y. M. Rustum Tumor Vascular Maturation and Improved Drug Delivery Induced by Methylselenocysteine Leads to Therapeutic Synergy with Anticancer Drugs Clin. Cancer Res., June 15, 2008; 14(12): 3926 - 3932. [Abstract] [Full Text] [PDF]

				I. M. Stefansson, H. B. Salvesen, and L. A. Akslen Vascular proliferation is important for clinical progress of endometrial cancer. Cancer Res., March 15, 2006; 66(6): 3303 - 3309. [Abstract] [Full Text] [PDF]

				T C Mineo, V Ambrogi, A Baldi, C Rabitti, P Bollero, B Vincenzi, and G Tonini Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer J. Clin. Pathol., June 1, 2004; 57(6): 591 - 597. [Abstract] [Full Text] [PDF]

				H. E. Turner, A. L. Harris, S. Melmed, and J. A. H. Wass Angiogenesis in Endocrine Tumors Endocr. Rev., October 1, 2003; 24(5): 600 - 632. [Abstract] [Full Text] [PDF]

				P. Wachsberger, R. Burd, and A. P. Dicker Tumor Response to Ionizing Radiation Combined with Antiangiogenesis or Vascular Targeting Agents: Exploring Mechanisms of Interaction Clin. Cancer Res., June 1, 2003; 9(6): 1957 - 1971. [Abstract] [Full Text] [PDF]

				A. Giatromanolaki, E. Sivridis, G. Minopoulos, A. Polychronidis, C. Manolas, C. Simopoulos, and M. I. Koukourakis Differential Assessment of Vascular Survival Ability and Tumor Angiogenic Activity in Colorectal Cancer Clin. Cancer Res., May 1, 2002; 8(5): 1185 - 1191. [Abstract] [Full Text] [PDF]

				M. J. Currie, S. P. Gunningham, C. Han, P. A. E. Scott, B. A. Robinson, A. L. Harris, and S. B. Fox Angiopoietin-1 Is Inversely Related to Thymidine Phosphorylase Expression in Human Breast Cancer, Indicating a Role in Vascular Remodeling Clin. Cancer Res., April 1, 2001; 7(4): 918 - 927. [Abstract] [Full Text]

				A. J. Marrogi, W. D. Travis, J. A. Welsh, M. A. Khan, H. Rahim, H. Tazelaar, P. Pairolero, V. Trastek, J. Jett, N. E. Caporaso, et al. Nitric Oxide Synthase, Cyclooxygenase 2, and Vascular Endothelial Growth Factor in the Angiogenesis of Non-Small Cell Lung Carcinoma Clin. Cancer Res., December 1, 2000; 6(12): 4739 - 4744. [Abstract] [Full Text]

				A. W. Griffioen and G. Molema Angiogenesis: Potentials for Pharmacologic Intervention in the Treatment of Cancer, Cardiovascular Diseases, and Chronic Inflammation Pharmacol. Rev., June 1, 2000; 52(2): 237 - 268. [Abstract] [Full Text] [PDF]