This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 Straume, O. Articles by Akslen, L. A. Search for Related Content PubMed PubMed Citation Articles by Straume, O. Articles by Akslen, L. A.

(American Journal of Pathology. 2002;160:1009-1019.)
© 2002 American Society for Investigative Pathology

Regular Articles

Importance of Vascular Phenotype by Basic Fibroblast Growth Factor, and Influence of the Angiogenic Factors Basic Fibroblast Growth Factor/Fibroblast Growth Factor Receptor-1 and Ephrin-A1/EphA2 on Melanoma Progression

From the Department of Pathology, The Gade Institute, HaukelandUniversity Hospital, Bergen, Norway

The expression of several angiogenic factors and receptors was examined in a series of vertical growth phase cutaneous melanomas using high-throughput tissue microarray technology and immunohistochemistry. The results were correlated with microvessel density, clinicopathological features, and patient survival. Expression of basic fibroblast growth factor (bFGF) was significantly associated with increased microvessel density. Also, we found an independent prognostic importance of vascular phenotype by endothelial cell expression of bFGF; cases with positive vessels had the best prognosis and these tumors revealed a low frequency of vascular invasion (14%) when compared with bFGF-negative vessels (47%). This bFGF-negative phenotype was significantly increased in metastatic lesions. Strong tumor cell expression of FLT-4, ephrin-A1, and EphA2 was associated with increased melanoma thickness, and ephrin-A1 staining was related to decreased survival (P = 0.039). Expression of EphA2 in tumor cells was associated with increased tumor cell proliferation (Ki-67 positivity), indicating possible autocrine growth stimulation. Thus, our findings indicate the presence of phenotypic diversity among tumor-associated vessels, and subgroups defined by bFGF expression may be of clinical importance. bFGF was associated with microvessel density, whereas the ephrin-A1/EphA2 pathway might also be important for tumor cell proliferation and patient survival.

This article has been cited by other articles:

				Y.-H. Liao, S.-M. Hsu, and P.-H. Huang ARMS Depletion Facilitates UV Irradiation Induced Apoptotic Cell Death in Melanoma Cancer Res., December 15, 2007; 67(24): 11547 - 11556. [Abstract] [Full Text] [PDF]

				K. Gravdal, O. J. Halvorsen, S. A. Haukaas, and L. A. Akslen A Switch from E-Cadherin to N-Cadherin Expression Indicates Epithelial to Mesenchymal Transition and Is of Strong and Independent Importance for the Progress of Prostate Cancer Clin. Cancer Res., December 1, 2007; 13(23): 7003 - 7011. [Abstract] [Full Text] [PDF]

				C. Cristina, G. Diaz-Torga, A. Gongora, M. C. Guida, M. I. Perez-Millan, A. Baldi, and D. Becu-Villalobos Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1341 - E1351. [Abstract] [Full Text] [PDF]

				Y. Chen, A. D. Leal, S. Patel, and D. H. Gorski The Homeobox Gene GAX Activates p21WAF1/CIP1 Expression in Vascular Endothelial Cells through Direct Interaction with Upstream AT-rich Sequences J. Biol. Chem., January 5, 2007; 282(1): 507 - 517. [Abstract] [Full Text] [PDF]

				H. Was, T. Cichon, R. Smolarczyk, D. Rudnicka, M. Stopa, C. Chevalier, J. J. Leger, B. Lackowska, A. Grochot, K. Bojkowska, et al. Overexpression of Heme Oxygenase-1 in Murine Melanoma: Increased Proliferation and Viability of Tumor Cells, Decreased Survival of Mice Am. J. Pathol., December 1, 2006; 169(6): 2181 - 2198. [Abstract] [Full Text] [PDF]

				K. Collett, G. E. Eide, J. Arnes, I. M. Stefansson, J. Eide, A. Braaten, T. Aas, A. P. Otte, and L. A. Akslen Expression of Enhancer of Zeste Homologue 2 Is Significantly Associated with Increased Tumor Cell Proliferation and Is a Marker of Aggressive Breast Cancer Clin. Cancer Res., February 15, 2006; 12(4): 1168 - 1174. [Abstract] [Full Text] [PDF]

				I. M. Bachmann, O. Straume, H. E. Puntervoll, M. B. Kalvenes, and L. A. Akslen Importance of P-Cadherin, {beta}-Catenin, and Wnt5a/Frizzled for Progression of Melanocytic Tumors and Prognosis in Cutaneous Melanoma Clin. Cancer Res., December 15, 2005; 11(24): 8606 - 8614. [Abstract] [Full Text] [PDF]

				M. Stapelberg, N. Gellert, E. Swettenham, M. Tomasetti, P. K. Witting, A. Procopio, and J. Neuzil {alpha}-Tocopheryl Succinate Inhibits Malignant Mesothelioma by Disrupting the Fibroblast Growth Factor Autocrine Loop: MECHANISM AND THE ROLE OF OXIDATIVE STRESS J. Biol. Chem., July 8, 2005; 280(27): 25369 - 25376. [Abstract] [Full Text] [PDF]

				H Iida, M Honda, H F Kawai, T Yamashita, Y Shirota, B-C Wang, H Miao, and S Kaneko Ephrin-A1 expression contributes to the malignant characteristics of {alpha}-fetoprotein producing hepatocellular carcinoma Gut, June 1, 2005; 54(6): 843 - 851. [Abstract] [Full Text] [PDF]

				X.-F. Wang, J. Z. Cui, S. S. Prasad, and J. A. Matsubara Altered Gene Expression of Angiogenic Factors Induced by Calcium-Mediated Dissociation of Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1508 - 1515. [Abstract] [Full Text] [PDF]

				C. J. Herrem, T. Tatsumi, K. S. Olson, K. Shirai, J. H. Finke, R. M. Bukowski, M. Zhou, A. L. Richmond, I. Derweesh, M. S. Kinch, et al. Expression of EphA2 is Prognostic of Disease-Free Interval and Overall Survival in Surgically Treated Patients with Renal Cell Carcinoma Clin. Cancer Res., January 1, 2005; 11(1): 226 - 231. [Abstract] [Full Text] [PDF]

				P. H. Thaker, M. Deavers, J. Celestino, A. Thornton, M. S. Fletcher, C. N. Landen, M. S. Kinch, P. A. Kiener, and A. K. Sood EphA2 Expression Is Associated with Aggressive Features in Ovarian Carcinoma Clin. Cancer Res., August 1, 2004; 10(15): 5145 - 5150. [Abstract] [Full Text] [PDF]

				I. M. Stefansson, H. B. Salvesen, and L. A. Akslen Prognostic Impact of Alterations in P-Cadherin Expression and Related Cell Adhesion Markers in Endometrial Cancer J. Clin. Oncol., April 1, 2004; 22(7): 1242 - 1252. [Abstract] [Full Text] [PDF]

				P. Dobrzanski, K. Hunter, S. Jones-Bolin, H. Chang, C. Robinson, S. Pritchard, H. Zhao, and B. Ruggeri Antiangiogenic and Antitumor Efficacy of EphA2 Receptor Antagonist Cancer Res., February 1, 2004; 64(3): 910 - 919. [Abstract] [Full Text] [PDF]

				P. V. Nantermet, J. Xu, Y. Yu, P. Hodor, D. Holder, S. Adamski, M. A. Gentile, D. B. Kimmel, S.-i. Harada, D. Gerhold, et al. Identification of Genetic Pathways Activated by the Androgen Receptor during the Induction of Proliferation in the Ventral Prostate Gland J. Biol. Chem., January 9, 2004; 279(2): 1310 - 1322. [Abstract] [Full Text] [PDF]

				M. Kunz, S. Moeller, D. Koczan, P. Lorenz, R. H. Wenger, M. O. Glocker, H.-J. Thiesen, G. Gross, and S. M. Ibrahim Mechanisms of Hypoxic Gene Regulation of Angiogenesis Factor Cyr61 in Melanoma Cells J. Biol. Chem., November 14, 2003; 278(46): 45651 - 45660. [Abstract] [Full Text] [PDF]

				S. E. Woodman, A. W. Ashton, W. Schubert, H. Lee, T. M. Williams, F. A. Medina, J. B. Wyckoff, T. P. Combs, and M. P. Lisanti Caveolin-1 Knockout Mice Show an Impaired Angiogenic Response to Exogenous Stimuli Am. J. Pathol., June 1, 2003; 162(6): 2059 - 2068. [Abstract] [Full Text] [PDF]

				O. Straume, D. G. Jackson, and L. A. Akslen Independent Prognostic Impact of Lymphatic Vessel Density and Presence of Low-Grade Lymphangiogenesis in Cutaneous Melanoma Clin. Cancer Res., January 1, 2003; 9(1): 250 - 256. [Abstract] [Full Text] [PDF]