c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival

被引:65
作者
Lee, Su Jin [1 ]
Lee, Jeeyun [1 ]
Park, Se Hoon [1 ]
Park, Joon Oh [1 ]
Lim, Ho Yeong [1 ]
Kang, Won Ki [1 ]
Park, Young Suk [1 ]
Kim, Seung Tae [1 ]
机构
[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, 81 Irwon Ro, Seoul 06351, South Korea
关键词
c-MET; Colorectal cancer; Immunohistochemistry; Prognosis; GENE AMPLIFICATION; RECEPTOR; EXPRESSION; ANGIOGENESIS; CHEMOTHERAPY; BEVACIZUMAB; METASTASIS; INHIBITORS; MUTATIONS; CETUXIMAB;
D O I
10.1016/j.clcc.2018.02.013
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mesenchymal-epithelial transition factor gene (c-MET) overexpression might be an important biomarker in colorectal cancer (CRC). We evaluated the incidence of c-MET overexpression and its prognostic significance in 255 patients with metastatic CRC. We found that 15.3% had c-MET overexpression and c-MET overexpression was associated with shorter survival. Introduction: Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). Patients and Methods: We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features and survival. Results: Primary tumor sites were 67 right-sided colon, 98 left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%) exhibited c-MET overexpression. There was no significant difference in the prevalence of c-MET overexpression according to primary site, histologic differentiation, molecular markers, or metastatic sites. In a comparison of the tumor response to first-line chemotherapy according to the level of c-MET expression, we found no significant difference in either partial response or disease control rate. In the survival analysis, patients with c-MET overexpression had significantly shorter overall survival (39 vs. 27 months; P=.018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7 months; P=.024). Conclusion: c-MET overexpression, which was detected in 39 CRC patients (15.3%) irrespective of primary sites or molecular markers, indicated a poor survival prognosis and predicted shorter PFS during bevacizumab treatment in patients with CRC. Further studies are warranted to elucidate the value of ceMET-targeted therapy in CRC patients. (C) 2018 The Authors. Published by Elsevier Inc.
引用
收藏
页码:165 / 169
页数:5
相关论文
共 31 条
[1]   c-MET immunostaining in colorectal carcinoma is associated with local disease recurrence [J].
Al-Maghrabi, Jaudah ;
Emam, Eman ;
Gomaa, Wafaey ;
Saggaf, Moaath ;
Buhmeida, Abdelbaset ;
Al-Qahtani, Mohammad ;
Al-Ahwal, Mahmoud .
BMC CANCER, 2015, 15
[2]   ESSENTIAL ROLE FOR THE C-MET RECEPTOR IN THE MIGRATION OF MYOGENIC PRECURSOR CELLS INTO THE LIMB BUD [J].
BLADT, F ;
RIETHMACHER, D ;
ISENMANN, S ;
AGUZZI, A ;
BIRCHMEIER, C .
NATURE, 1995, 376 (6543) :768-771
[3]   The HGF/c-METPathway Is a Driver and Biomarker of VEGFR-inhibitor Resistance and Vascular Remodeling in Non-Small Cell Lung Cancer [J].
Cascone, Tina ;
Xu, Li ;
Lin, Heather Y. ;
Liu, Wenbin ;
Tran, Hai T. ;
Liu, Yuan ;
Howells, Kathryn ;
Haddad, Vincent ;
Hanrahan, Emer ;
Nilsson, Monique B. ;
Cortez, Maria A. ;
Giri, Uma ;
Kadara, Humam ;
Saigal, Babita ;
Park, Yun-Yong ;
Peng, Weiyi ;
Lee, Ju-Seog ;
Ryan, Anderson J. ;
Juergensmeier, Juliane M. ;
Herbst, Roy S. ;
Wang, Jing ;
Langley, Robert R. ;
Wistuba, Ignacio I. ;
Lee, Jack J. ;
Heymach, John V. .
CLINICAL CANCER RESEARCH, 2017, 23 (18) :5489-5501
[4]   HGF receptor up-regulation contributes to the angiogenic phenotype of human endothelial cells and promotes angiogenesis in vitro [J].
Ding, SL ;
Merkulova-Rainon, T ;
Han, ZC ;
Tobelem, G .
BLOOD, 2003, 101 (12) :4816-4822
[5]   Panitumumab-FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer [J].
Douillard, Jean-Yves ;
Oliner, Kelly S. ;
Siena, Salvatore ;
Tabernero, Josep ;
Burkes, Ronald ;
Barugel, Mario ;
Humblet, Yves ;
Bodoky, Gyorgy ;
Cunningham, David ;
Jassem, Jacek ;
Rivera, Fernando ;
Kocakova, Ilona ;
Ruff, Paul ;
Blasinska-Morawiec, Maria ;
Smakal, Martin ;
Canon, Jean Luc ;
Rother, Mark ;
Williams, Richard ;
Rong, Alan ;
Wiezorek, Jeffrey ;
Sidhu, Roger ;
Patterson, Scott D. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (11) :1023-1034
[6]   Targeting MET in Lung Cancer: Will Expectations Finally Be MET? [J].
Drilon, Alexander ;
Cappuzzo, Federico ;
Ignatius, Sai-Hong ;
Camidge, D. Ross .
JOURNAL OF THORACIC ONCOLOGY, 2017, 12 (01) :15-26
[7]   High c-Met expression is a negative prognostic marker for colorectal cancer: a meta-analysis [J].
Gao, HeLi ;
Guan, Mei ;
Sun, Zhao ;
Bai, ChunMei .
TUMOR BIOLOGY, 2015, 36 (02) :515-520
[8]   FAK, CD44v6, c-Met and EGFR in colorectal cancer parameters: tumour progression, metastasis, patient survival and receptor crosstalk [J].
Garouniatis, Alexandros ;
Zizi-Sermpetzoglou, Adamantia ;
Rizos, Spyros ;
Kostakis, Alkiviadis ;
Nikiteas, Nikolaos ;
Papavassiliou, Athanasios G. .
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, 2013, 28 (01) :9-18
[9]   MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas [J].
Ha, Sang Y. ;
Lee, Jeeyun ;
Kang, So Y. ;
Do, In-Gu ;
Ahn, Soomin ;
Park, Joon O. ;
Kang, Won K. ;
Choi, Min-Gew ;
Sohn, Tae S. ;
Bae, Jae M. ;
Kim, Sung ;
Kim, Minji ;
Kim, Seonwoo ;
Park, Cheol K. ;
Ou, Sai-Hong Ignatius ;
Kim, Kyoung-Mee .
MODERN PATHOLOGY, 2013, 26 (12) :1632-1641
[10]   Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer [J].
Hurwitz, H ;
Fehrenbacher, L ;
Novotny, W ;
Cartwright, T ;
Hainsworth, J ;
Heim, W ;
Berlin, J ;
Baron, A ;
Griffing, S ;
Holmgren, E ;
Ferrara, N ;
Fyfe, G ;
Rogers, B ;
Ross, R ;
Kabbinavar, F .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (23) :2335-2342