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2002 Scientific Report

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patients and confirmed

patients and confirmed that Met expression was present in all of 41 prostate cancer metastases to bone within this cohort (Figure 2). In collaboration with Nadia Harbeck and Ernest Lengyel, we have conducted a retrospective pilot study using breast cancer tissue obtained from about 40 patients to investigate whether Met-HGF/SF and HER-2/neu are coexpressed in HER-2-positive tumors. We correlated the results of immunohistochemical evaluation of tissue samples in our two laboratories with other clinicopathological data. We found that neither Met nor HER-2 expression in primary tumors correlated with established prognostic factors such as age, lymph node involvement, estrogen receptor expression, progesterone receptor expression, tumor size, or tumor grading. However, Met overexpression alone identified high-risk patients independent of HER-2 expression. Median disease-free survival associated with c-Met overexpressing tumors was 8 months, compared to 53 months in remaining Figure 2. Met expression (arrow, brown) by prostate cancer metastasis in human bone patients (p = 0.031; RR 3.1). We conclude that Met overexpression is associated with significantly diminished disease-free survival (DFS) and, in the majority of cases, this is independent of HER-2 overexpression. External Collaborators Michael Clague, University of Liverpool, United Kingdom Milton Gross, Department of Veterans Affairs Healthcare System and University of Michigan, Ann Arbor Nadia Harbeck and Ernest Lengyel, Technische Universität, Munich, Germany Ruth Heimann and Samuel Hellman, University of Chicago, Illinois Richard Jove, H. Lee Moffitt Cancer and Research Institute, Tampa, Florida Beatrice Knudsen, Fred Hutchinson Cancer Research Center, Seattle, Washington Len Neckers and Bert Zbar, National Cancer Institute, Bethesda, Maryland Brian Ross, University of Michigan, Ann Arbor Peter Schirmacher, University of Cologne, Germany David Waters, Gerald P. Murphy Cancer Foundation, Seattle, Washington David Wenkert, Michigan State University, East Lansing Robert Wondergem, East Tennessee State University, Johnson City 47

Publications Collazo, Carmen M., George S. Yap, Gregory D. Sempowski, Kimberly C. Lusby, Lino Tessarollo, George F. Vande Woude, Alan Sher, and Gregory A. Taylor. 2001. Inactivation of LRG-47 and IRG-47 reveals a family of interferon g–inducible genes with essential, pathogen-specific roles in resistance to infection. Journal of Experimental Medicine 194(2): 181–188. Furge, Kyle A., David Kiewlich, Phuong Le, My Nga Vo, Michel Faure, Anthony R. Howlett, Kenneth E. Lipson, George F. Vande Woude, and Craig P. Webb. 2001. Suppression of Rasmediated tumorigenicity and metastasis through inhibition of the Met receptor tyrosine kinase. Proceedings of the National Academy of Sciences U.S.A. 98(19): 10722–10727. Hay, Rick V., Brian Cao, R. Scot Skinner, Ling-Mei Wang, Yanli Su, James H. Resau, George F. Vande Woude, and Milton Gross. 2002. Radioimmunoscintigraphy of tumors autocrine for human Met and hepatocyte growth factor/scatter factor. Molecular Imaging 1(1): 56–62. Knudsen, Beatrice S., Glenn A. Gmyrek, J. Inra, D.S. Scherr, E. Darracott Vaughan, D.M. Nanus, M.W. Kattan, W.L. Gerald, and George F. Vande Woude. In press. High expression of the Met receptor in prostate cancer metastasis to bone. Urology. Koo, Han-Mo, Matt VanBrocklin, MaryJane McWilliams, Stephan H. Leppla, Nicholas S. Duesbery, and George F. Vande Woude. 2002. Apoptosis and melanogenesis in human melanoma cells induced by anthrax lethal factor inactivation of mitogen-activated protein kinase kinase. Proceedings of the National Academy of Sciences U.S.A. 99(5): 3052–3057. Qian, Chao-Nan, Xiang Guo, Brian Cao, Eric J. Kort, Chong-Chou Lee, Jindong Chen, Ling-Mei Wang, Wei-Yuan Mai, Hua-Qing Min, Ming-Huang Hong, George F. Vande Woude, James H. Resau, and Bin T. Teh. 2002. Met protein expression level correlates with survival in patients with late-stage nasopharyngeal carcinoma. Cancer Research 62(2): 589–596. Webb, Craig P., and George F. Vande Woude. 2002. Met gene. In Wiley Encyclopedia of Molecular Medicine, Haig H. Kazazian, ed. New York: Wiley, pp. 2049–2051. Zhang, Yu-Wen, Ling-Mei Wang, R. Jove, and George F. Vande Woude. 2002. Requirement of Stat3 signaling for HGF/SF-Met-mediated tumorigenesis. Oncogene 21(2): 217–226. From left to right: Kaufman, Gao, Zhang, I. Tsarfaty, Shinomiya, Hay, G. Tsarfaty, Su, Vande Woude, Bruch, Gustafson 48

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