Comprehensive molecular analyses of lung adenocarcinoma with regard to the epidermal growth factor receptor, K-ras, MET, and hepatocyte growth factor status.

作者: Takamitsu Onitsuka , Hidetaka Uramoto , Kenji Ono , Mitsuhiro Takenoyama , Takeshi Hanagiri

DOI: 10.1097/JTO.0B013E3181D0A4DB

关键词:

摘要: Background The mutation and amplification of oncogenic genes are associated with carcinogenesis tumor growth. purpose this study was to clarify the role epidermal growth factor receptor (EGFR), K- ras , MET, hepatocyte (HGF) status in lung adenocarcinoma. Methods Tumor specimens were collected from 183 patients who underwent a complete resection for adenocarcinoma 2003 2007 our department. genetic EGFR investigated by polymerase chain reaction (PCR)-based analyses. Immunohistochemistry real time PCR assays used evaluate MET gene regarding tyrosine phosphorylation amplification, respectively. HGF evaluated immunohistochemistry. Results mutations detected 64 (35%) 17 (9%), 1234/1235 (p-MET 1234/1235) identified 12 (7%) 8 (4%) specimens, Positive expression 104 (57%). An found significantly more frequently females tumors wild type without amplification. A p-MET positive HGF. multivariate survival analysis demonstrated that negative 1234/1235, independently an increased risk poor survival. Conclusions occurrence EGFR/ might be mutually exclusive suggesting several distinct mechanisms development may useful marker predicting prognosis surgical

参考文章(40)
Patrick C Ma, Gautam Maulik, James Christensen, Ravi Salgia, c-Met: Structure, functions and potential for therapeutic inhibition Cancer and Metastasis Reviews. ,vol. 22, pp. 309- 325 ,(2003) , 10.1023/A:1023768811842
Stephen L. Graziano, Gary P. Gamble, Nancy B. Newman, Lynn Z. Abbott, Michelle Rooney, Sulagna Mookherjee, Melissa L. Lamb, Leslie J. Kohman, Bernard J. Poiesz, Prognostic Significance of K-ras Codon 12 Mutations in Patients With Resected Stage I and II Non–Small-Cell Lung Cancer Journal of Clinical Oncology. ,vol. 17, pp. 668- 668 ,(1999) , 10.1200/JCO.1999.17.2.668
Hidetaka Uramoto, Kenji Sugio, Tsunehiro Oyama, Masakazu Sugaya, Takeshi Hanagiri, Kosei Yasumoto, Resistance to gefitinib. International Journal of Clinical Oncology. ,vol. 11, pp. 487- 491 ,(2006) , 10.1007/S10147-006-0609-Y
Takamitsu Onitsuka, Hidetaka Uramoto, Naohiro Nose, Mitsuhiro Takenoyama, Takeshi Hanagiri, Kenji Sugio, Kosei Yasumoto, Acquired resistance to gefitinib: The contribution of mechanisms other than the T790M, MET, and HGF status Lung Cancer. ,vol. 68, pp. 198- 203 ,(2010) , 10.1016/J.LUNGCAN.2009.05.022
Takayuki Kosaka, Yasushi Yatabe, Hideki Endoh, Kimihide Yoshida, Toyoaki Hida, Masahiro Tsuboi, Hirohito Tada, Hiroyuki Kuwano, Tetsuya Mitsudomi, Analysis of Epidermal Growth Factor Receptor Gene Mutation in Patients with Non–Small Cell Lung Cancer and Acquired Resistance to Gefitinib Clinical Cancer Research. ,vol. 12, pp. 5764- 5769 ,(2006) , 10.1158/1078-0432.CCR-06-0714
Tomoyuki Goya, Hisao Asamura, Hirokuni Yoshimura, Harubumi Kato, Kaoru Shimokata, Ryosuke Tsuchiya, Yasunori Sohara, Toshimichi Miya, Etsuo Miyaoka, Japanese Joint Committee of Lung Cancer Registry, None, Prognosis of 6644 resected non-small cell lung cancers in Japan: A Japanese lung cancer registry study Lung Cancer. ,vol. 50, pp. 227- 234 ,(2005) , 10.1016/J.LUNGCAN.2005.05.021
Clifton F. Mountain, Revisions in the International System for Staging Lung Cancer Chest. ,vol. 111, pp. 1710- 1717 ,(1997) , 10.1378/CHEST.111.6.1710
J. A. Engelman, K. Zejnullahu, T. Mitsudomi, Y. Song, C. Hyland, J. O. Park, N. Lindeman, C.-M. Gale, X. Zhao, J. Christensen, T. Kosaka, A. J. Holmes, A. M. Rogers, F. Cappuzzo, T. Mok, C. Lee, B. E. Johnson, L. C. Cantley, P. A. Janne, MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling Science. ,vol. 316, pp. 1039- 1043 ,(2007) , 10.1126/SCIENCE.1141478