with outcome in a cohort of trastuzumab- treated breast cancer patients. Clin Cancer Res 16: 4226–4235. 12. Larson JS, Goodman L, Tan Y, Defazio-Eli L, Paquet AC, et al. (2010) Analytical validation of a highly sensitive, accurate, and reproducible assay (HERmark) for measurement of total Her2 and Her2 homodimers in FFPE breast cancer tumor specimens. Pathol Res Int. pp 814176. 13. Kong-Beltran M, Stamos J, Wickramasinghe D (2004) The Sema domain of Met is necessary for receptor dimerization and activation. Cancer Cell 6: 75–84. 14. Dua R, Zhang, J, Nhonthachit P, Penuel E, Petropoulos C, et al. (2010) EGFR overexpression and activation in high Her2, ER negative cell line induces trastuzumab resistance. Breast Cancer Res Treat 122: 685–697. 15. Jain A, Penuel E, Mink S, Schmidt A, Hodge K, et al. (2010) Her kinase axis receptor dimer partner switching occurs in response to EGFR tyrosine kinase inhibition despite failure to block cellular proliferation. Cancer Res 70: 1989–1999. 16. Sawada K, Radjabi AR, Shinomiya N, Kistner E, Kenny H, et al. (2007) c-Met overexpression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion. Cancer Res 67: 1670–1679. 17. Lengyel E, Prechtel D, Resau JH, Gauger K, Welk A, et al. (2005) c-MET overexpression in node-positive breast cancer identifies patients with poor clinical outcome independent of Her2/neu. Int J Cancer 113: 678–682. 18. Kong DS, Song SY, Kim DH, Joo KM, Yoo JS, et al. (2009) Prognostic significance of c-Met expression in glioblastomas. Cancer 115: 140–148. 19. Chistensen JG, Schreck R, Burrows J, Kuruganti P, Chan E, et al. (2003) A selective small molecule inhibitor of c-Met kinase inhibits c-Met dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res 63: 7345–7355. 20. Ma PC, Jagadeeswaran R, Jagadeesh S, Tretiakova MS, Nallasura V, et al. (2005) Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res 65: 1479–1488. 21. Go¨tte M, Kersting C, Radke I, Radke I, Kiesel L, et al. (2007) An expression signature of syndecan-1 (CD138), E-cadherin and c-Met is associated with factors of angiogenesis and lymphangiogenesis in ductal breast carcinoma in situ. Breast Cancer Res 9: doi 10.1186/bcr1641. 22. Gupta A, Karakiewicz PI, Roehrborn CG, Lotan Y, Zlotta AR, et al. (2008) Predictive value of plasma hepatocyte growth factor/scatter factor in patients with clinically localized prostate cancer. Clin Cancer Res 14: 7385–7390. 23. Siegfried JM, Weissfeld LA, Singh-Kaw P, Weyant RJ, Testa JR, et al. (1997) Association of immunoreactive hepatocyte growth factor with poor survival in resectable non-small cell lung cancer. Cancer Res 57: 433–439. 24. Nakamura T, Matsumoto K, Kiritoshi A, Tano Y, Nakamura T (1997) Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors Detection of Receptor Activation in FFPE Specimens affects invasive growth of tumor cells: In vitro analysis of tumor-stromal interactions. Cancer Res 57: 3305–3313. 25. Koochekpour S, Jeffers M, Rulong S, Taylor G, Klinberg E, et al. (1997) Met and hepatocyte growth factor/scatter expession in human gliomas. Cancer Res 57: 5391–5398. 26. Yano S, Wang W, Matsumoto K, Sakurama H, Nakamura T, et al. (2008) Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res 68: 9479–9487. 27. Kong-Beltran M, Seshagiri S, Zha J, Zhu W, Bhawe K, et al. (2006) Somatic mutations lead to an oncogenic deletion of Met in lung cancer. Cancer Res 66: 283–289. 28. Desmedt C, Sperinde J, Piette F, Huang W, Jin X, et al. (2009) Quantitation of Her2 and Her2:Her2 dimers and differential survival in a cohort of metastatic breast cancer patients carefully selected for trastuzumab treatment by FISH. Diag Mol Pathol 18: 22–29. 29. Pozner-Moulis S, Cregger M, Camp RL, Rimm DL (2006) Antibody validation by quantitative analysis of protein expression of Met in breast cancer as a model. Lab Investigation 87: 251–260. 30. Knowles LM, Stabile LP, Egloff AM, Rothstein ME, Thomas SM, et al. (2009) HGF and c-Met participate in paracrine tumorigenic pathways in head and neck squamous cell cancer. Cancer Res 15: 3740–3750. 31. Miyata Y, Kanetake H, Kanda S (2006) Presence of phosphorylated hepatocyte growth factor receptor/c-Met is associated with tumor progression and survival in patients with conventional renal cell carcinoma. Clin Cancer Res 16: 4876–4881. 32. Gordon MS, Sweeney CJ, Mendelson DS, Eckhardt SG, Anderson A, et al. (2010) Safety, pharmacokinetics, and pharmacodynamics of AMG102, a fully human hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in- human study of patients with advanced solid tumors. Clin Cancer Res 16: 699–710. 33. Salgia R, Peterson A, Eppler S, et al. (2008) A phase I, open label, dose- escalation study of the safety and pharmacology of MetMab, a monovalent antagonist antibody to the receptor c-Met, administered IV in patients with locally advanced or metastatic solid tumors [abstract 411]. Geneva, Switzerland: Proceedings of the 20th Annual AACR-NCI-EORTC international conference: Molecular Targets and Cancer Therapeutics Oct 21-24. 34. Yap TA, Harris D, Barriuso J, et al. (2008) Phase I trial to determine the dose range for the c-Met inhibitor ARQ197 that inhibits c-Met and FAK phosphorylation, when administered by an oral twice-a-day schedule. J Clin Oncol 26(15S): 3584 p. PLoS ONE | www.plosone.org 17 January 2011 | Volume 6 | Issue 1 | e15932