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Clinicopathological Significance and Diagnostic Accuracy of c-MET Expression by Immunohistochemistry in Gastric Cancer: A Meta-Analysis

  • Pyo, Jung-Soo (Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Kang, Guhyun (Department of Pathology, Inje University Sanggye Paik Hospital) ;
  • Cho, Hyunjin (Department of Surgery, Inje University Sanggye Paik Hospital)
  • Received : 2016.04.28
  • Accepted : 2016.06.10
  • Published : 2016.09.30

Abstract

Purpose: The aim of the present study was to elucidate the clinicopathological significance and diagnostic accuracy of immunohistochemistry (IHC) for determining the mesenchymal epidermal transition (c-MET) expression in patients with gastric cancer (GC). Materials and Methods: The present meta-analysis investigated the correlation between c-MET expression as determined by IHC and the clinicopathological parameters in 8,395 GC patients from 37 studies that satisfied the eligibility criteria. In addition, a concordance analysis was performed between c-MET expression as determined by IHC and c-MET amplification, and the diagnostic test accuracy was reviewed. Results: The estimated rate of c-MET overexpression was 0.403 (95% confidence interval [CI], 0.327~0.484) and it was significantly correlated with male patients, poor differentiation, lymph node metastasis, higher TNM stage, and human epidermal growth factor receptor 2 (HER2) positivity in IHC analysis. There was a significant correlation between c-MET expression and worse overall survival rate (hazard ratio, 1.588; 95% CI, 1.266~1.992). The concordance rates between c-MET expression and c-MET amplification were 0.967 (95% CI, 0.916~0.987) and 0.270 (95% CI, 0.173~0.395) for cases with non-overexpressed and overexpressed c-MET, respectively. In the diagnostic test accuracy review, the pooled sensitivity and specificity were 0.56 (95% CI, 0.50~0.63) and 0.79 (95% CI, 0.77~0.81), respectively. Conclusions: The c-MET overexpression as determined by IHC was significantly correlated with aggressive tumor behavior and positive IHC status for HER2 in patients with GC. In addition, the c-MET expression status could be useful in the screening of c-MET amplification in patients with GC.

Keywords

References

  1. Bosman FT, Carneiro F, Hruban RH, Theise ND, eds. WHO Classification of Tumours of the Digestive System. 4th ed. Lyon: International Agency for Research on Cancer, 2010.
  2. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 2006;24:2137-2150. https://doi.org/10.1200/JCO.2005.05.2308
  3. Lee KH, Lee HE, Cho SJ, Cho YJ, Lee HS, Kim JH, et al. Immunohistochemical analysis of cell cycle-related molecules in gastric carcinoma: prognostic significance, correlation with clinicopathological parameters, proliferation and apoptosis. Pathobiology 2008;75:364-372. https://doi.org/10.1159/000164221
  4. Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol 2008;19:1523-1529. https://doi.org/10.1093/annonc/mdn169
  5. Ishii HH, Gobe GC, Ebihara Y. p53 is an indicator of tumor progression in early but not advanced gastric carcinomas. Hepatogastroenterology 2007;54:2159-2163.
  6. Kim JH, Kim MK, Lee HE, Cho SJ, Cho YJ, Lee BL, et al. Constitutive phosphorylation of the FOXO1A transcription factor as a prognostic variable in gastric cancer. Mod Pathol 2007;20:835-842. https://doi.org/10.1038/modpathol.3800789
  7. Xing X, Tang YB, Yuan G, Wang Y, Wang J, Yang Y, et al. The prognostic value of E-cadherin in gastric cancer: a meta-analysis. Int J Cancer 2013;132:2589-2596. https://doi.org/10.1002/ijc.27947
  8. Lieto E, Ferraraccio F, Orditura M, Castellano P, Mura AL, Pinto M, et al. Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients. Ann Surg Oncol 2008;15:69-79. https://doi.org/10.1245/s10434-007-9596-0
  9. Inokuchi M, Otsuki S, Fujimori Y, Sato Y, Nakagawa M, Kojima K. Clinical significance of MET in gastric cancer. World J Gastrointest Oncol 2015;7:317-327. https://doi.org/10.4251/wjgo.v7.i11.317
  10. Liu X, Newton RC, Scherle PA. Developing c-MET pathway inhibitors for cancer therapy: progress and challenges. Trends Mol Med 2010;16:37-45. https://doi.org/10.1016/j.molmed.2009.11.005
  11. Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: rationale and progress. Nat Rev Cancer 2012;12:89-103. https://doi.org/10.1038/nrc3205
  12. Pyo JS, Sohn JH, Kim WH. Concordance rate between HER2 immunohistochemistry and in situ hybridization in gastric carcinoma: systematic review and meta-analysis. Int J Biol Markers 2016;31:e1-e10. https://doi.org/10.5301/jbm.5000171
  13. Betts G, Valentine H, Pritchard S, Swindell R, Williams V, Morgan S, et al. FGFR2, HER2 and cMet in gastric adenocarcinoma: detection, prognostic significance and assessment of downstream pathway activation. Virchows Arch 2014;464:145-156. https://doi.org/10.1007/s00428-013-1517-y
  14. Catenacci DV, Cervantes G, Yala S, Nelson EA, El-Hashani E, Kanteti R, et al. RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma. Cancer Biol Ther 2011;12:9-46. https://doi.org/10.4161/cbt.12.1.15747
  15. Choi J, Lee HE, Kim MA, Jang BG, Lee HS, Kim WH. Analysis of MET mRNA expression in gastric cancers using RNA in situ hybridization assay: its clinical implication and comparison with immunohistochemistry and silver in situ hybridization. PLoS One 2014;9:e111658. https://doi.org/10.1371/journal.pone.0111658
  16. Drebber U, Baldus SE, Nolden B, Grass G, Bollschweiler E, Dienes HP, et al. The overexpression of c-met as a prognostic indicator for gastric carcinoma compared to p53 and p21 nuclear accumulation. Oncol Rep 2008;19:1477-1483.
  17. Fuse N, Kuboki Y, Kuwata T, Nishina T, Kadowaki S, Shinozaki E, et al. Prognostic impact of HER2, EGFR, and c-MET status on overall survival of advanced gastric cancer patients. Gastric Cancer 2016;19:183-191. https://doi.org/10.1007/s10120-015-0471-6
  18. Guo T, Yang J, Yao J, Zhang Y, Da M, Duan Y. Expression of MACC1 and c-Met in human gastric cancer and its clinical significance. Cancer Cell Int 2013;13:121. https://doi.org/10.1186/1475-2867-13-121
  19. Ha SY, Lee J, Jang J, Hong JY, Do IG, Park SH, et al. HER2-positive gastric cancer with concomitant MET and/or EGFR overexpression: a distinct subset of patients for dual inhibition therapy. Int J Cancer 2015;136:1629-1635. https://doi.org/10.1002/ijc.29159
  20. Han SU, Lee HY, Lee JH, Kim WH, Nam H, Kim H, et al. Modulation of E-cadherin by hepatocyte growth factor induces aggressiveness of gastric carcinoma. Ann Surg 2005;242:676-683. https://doi.org/10.1097/01.sla.0000186171.85804.fe
  21. Heideman DA, Snijders PJ, Bloemena E, Meijer CJ, Offerhaus GJ, Meuwissen SG, et al. Absence of tpr-met and expression of c-met in human gastric mucosa and carcinoma. J Pathol 2001;194:428-435. https://doi.org/10.1002/path.934
  22. Huang TJ, Wang JY, Lin SR, Lian ST, Hsieh JS. Overexpression of the c-met protooncogene in human gastric carcinoma: correlation to clinical features. Acta Oncol 2001;40:638-643. https://doi.org/10.1080/028418601750444204
  23. Janjigian YY, Tang LH, Coit DG, Kelsen DP, Francone TD, Weiser MR, et al. MET expression and amplification in patients with localized gastric cancer. Cancer Epidemiol Biomarkers Prev 2011;20:1021-1027. https://doi.org/10.1158/1055-9965.EPI-10-1080
  24. Kang BW, Lee D, Chung HY, Han JH, Kim YB. Tetraspanin CD151 expression associated with prognosis for patients with advanced gastric cancer. J Cancer Res Clin Oncol 2013;139:1835-1843. https://doi.org/10.1007/s00432-013-1503-4
  25. Kijima Y, Hokita S, Yoshinaka H, Itoh T, Koriyama C, Eizuru Y, et al. Amplification and overexpression of c-met gene in Epstein-Barr virus-associated gastric carcinomas. Oncology 2002;62:60-65. https://doi.org/10.1159/000048248
  26. Koh YW, Hur H, Lee D. Increased MACC1 expression indicates a poor prognosis independent of MET expression in gastric adenocarcinoma. Pathol Res Pract 2016;212:93-100. https://doi.org/10.1016/j.prp.2015.11.018
  27. Kubicka S, Claas C, Staab S, Kuhnel F, Zender L, Trautwein C, et al. p53 mutation pattern and expression of c-erbB2 and cmet in gastric cancer: relation to histological subtypes, Helicobacter pylori infection, and prognosis. Dig Dis Sci 2002;47:114-121. https://doi.org/10.1023/A:1013275706401
  28. Kuboki Y, Yamashita S, Niwa T, Ushijima T, Nagatsuma A, Kuwata T, et al. Comprehensive analyses using next-generation sequencing and immunohistochemistry enable precise treatment in advanced gastric cancer. Ann Oncol 2016;27:127-133. https://doi.org/10.1093/annonc/mdv508
  29. Kurokawa Y, Matsuura N, Kawabata R, Nishikawa K, Ebisui C, Yokoyama Y, et al. Prognostic impact of major receptor tyrosine kinase expression in gastric cancer. Ann Surg Oncol 2014;21 Suppl 4:S584-S590. https://doi.org/10.1245/s10434-014-3690-x
  30. Lee J, Seo JW, Jun HJ, Ki CS, Park SH, Park YS, et al. Impact of MET amplification on gastric cancer: possible roles as a novel prognostic marker and a potential therapeutic target. Oncol Rep 2011;25:1517-1524.
  31. Lee SJ, Lee J, Sohn I, Mao M, Kai W, Park CK, et al. A survey of c-MET expression and amplification in 287 patients with hepatocellular carcinoma. Anticancer Res 2013;33:5179-5186.
  32. Li Y, Chen CQ, He YL, Cai SR, Yang DJ, He WL, et al. Abnormal expression of E-cadherin in tumor cells is associated with poor prognosis of gastric carcinoma. J Surg Oncol 2012;106:304-310. https://doi.org/10.1002/jso.23008
  33. Liu YJ, Shen D, Yin X, Gavine P, Zhang T, Su X, et al. HER2, MET and FGFR2 oncogenic driver alterations define distinct molecular segments for targeted therapies in gastric carcinoma. Br J Cancer 2014;110:1169-1178. https://doi.org/10.1038/bjc.2014.61
  34. Ma J, Ma J, Meng Q, Zhao ZS, Xu WJ. Prognostic value and clinical pathology of MACC-1 and c-MET expression in gastric carcinoma. Pathol Oncol Res 2013;19:821-832. https://doi.org/10.1007/s12253-013-9650-0
  35. Metzger ML, Behrens HM, Boger C, Haag J, Kruger S, Rocken C. MET in gastric cancer: discarding a 10% cutoff rule. Histopathology 2016;68:241-253. https://doi.org/10.1111/his.12745
  36. Nagatsuma AK, Aizawa M, Kuwata T, Doi T, Ohtsu A, Fujii H, et al. Expression profiles of HER2, EGFR, MET and FGFR2 in a large cohort of patients with gastric adenocarcinoma. Gastric Cancer 2015;18:227-238. https://doi.org/10.1007/s10120-014-0360-4
  37. Nakajima M, Sawada H, Yamada Y, Watanabe A, Tatsumi M, Yamashita J, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer 1999;85:1894-1902. https://doi.org/10.1002/(SICI)1097-0142(19990501)85:9<1894::AID-CNCR3>3.0.CO;2-J
  38. Paliga A, Marginean H, Tessier-Cloutier B, Purgina B, Jonker D, Marginean EC. The prognostic significance of c-MET and EGFR overexpression in resected gastric adenocarcinomas. Am J Clin Oncol 2015. doi: 10.1097/COC.0000000000000202 [In print].
  39. Peng Z, Li Z, Gao J, Lu M, Gong J, Tang ET, et al. Tumor MET expression and gene amplification in Chinese patients with locally advanced or metastatic gastric or gastroesophageal junction cancer. Mol Cancer Ther 2015;14:2634-2641. https://doi.org/10.1158/1535-7163.MCT-15-0108
  40. Retterspitz MF, Monig SP, Schreckenberg S, Schneider PM, Holscher AH, Dienes HP, et al. Expression of {beta}-catenin, MUC1 and c-met in diffuse-type gastric carcinomas: correlations with tumour progression and prognosis. Anticancer Res 2010;30:4635-4641.
  41. Sotoudeh K, Hashemi F, Madjd Z, Sadeghipour A, Molanaei S, Kalantary E. The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays. Diagn Pathol 2012;7:57. https://doi.org/10.1186/1746-1596-7-57
  42. Sun Y, Li JY, He JS, Zhou LX, Chen K. Tissue microarray analysis of multiple gene expression in intestinal metaplasia, dysplasia and carcinoma of the stomach. Histopathology 2005;46:505-514. https://doi.org/10.1111/j.1365-2559.2005.02111.x
  43. Tang Z, Zhao M, Ji J, Yang G, Hu F, He J, et al. Overexpression of gastrin and c-met protein involved in human gastric carcinomas and intestinal metaplasia. Oncol Rep 2004;11:333-339.
  44. Taniguchi K, Yonemura Y, Nojima N, Hirono Y, Fushida S, Fujimura T, et al. The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor. Cancer 1998;82:2112-2122. https://doi.org/10.1002/(SICI)1097-0142(19980601)82:11<2112::AID-CNCR5>3.0.CO;2-X
  45. Wu JG, Yu JW, Wu HB, Zheng LH, Ni XC, Li XQ, et al. Expressions and clinical significances of c-MET, p-MET and E2f-1 in human gastric carcinoma. BMC Res Notes 2014;7:6. https://doi.org/10.1186/1756-0500-7-6
  46. Yun C, Gang L, Rongmin G, Xu W, Xuezhi M, Huanqiu C. Essential role of Her3 in two signaling transduction patterns: Her2/Her3 and MET/Her3 in proliferation of human gastric cancer. Mol Carcinog 2015;54:1700-1709. https://doi.org/10.1002/mc.22241
  47. Zhang Z, Wang J, Ji D, Wang C, Liu R, Wu Z, et al. Functional genetic approach identifies MET, HER3, IGF1R, INSR pathways as determinants of lapatinib unresponsiveness in HER2- positive gastric cancer. Clin Cancer Res 2014;20:4559-4573. https://doi.org/10.1158/1078-0432.CCR-13-3396
  48. Zhao J, Zhang X, Xin Y. Up-regulated expression of Ezrin and c-Met proteins are related to the metastasis and prognosis of gastric carcinomas. Histol Histopathol 2011;26:1111-1120.
  49. Zhu C, Xu J, Li M, Zhao G, Cao H. Heterogeneity of c-Met expression in Chinese gastric cancer patients. Hum Pathol 2015;46:1901-1907. https://doi.org/10.1016/j.humpath.2015.06.025
  50. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 1998;17:2815-2834. https://doi.org/10.1002/(SICI)1097-0258(19981230)17:24<2815::AID-SIM110>3.0.CO;2-8
  51. Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 1985;27:335-371. https://doi.org/10.1016/S0033-0620(85)80003-7
  52. Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 2006;6:31. https://doi.org/10.1186/1471-2288-6-31
  53. Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: dataanalytic approaches and some additional considerations. Stat Med 1993;12:1293-1316. https://doi.org/10.1002/sim.4780121403
  54. Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, et al. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol 2014;15:1007-1018. https://doi.org/10.1016/S1470-2045(14)70023-3
  55. Peng Z, Zhu Y, Wang Q, Gao J, Li Y, Li Y, et al. Prognostic significance of MET amplification and expression in gastric cancer: a systematic review with meta-analysis. PLoS One 2014;9:e84502. https://doi.org/10.1371/journal.pone.0084502
  56. Yu S, Yu Y, Zhao N, Cui J, Li W, Liu T. C-Met as a prognostic marker in gastric cancer: a systematic review and meta-analysis. PLoS One 2013;8:e79137. https://doi.org/10.1371/journal.pone.0079137
  57. Agarwal S, Zerillo C, Kolmakova J, Christensen JG, Harris LN, Rimm DL, et al. Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells. Br J Cancer 2009;100:941-949. https://doi.org/10.1038/sj.bjc.6604937
  58. Garrett JT, Arteaga CL. Resistance to HER2-directed antibodies and tyrosine kinase inhibitors: mechanisms and clinical implications. Cancer Biol Ther 2011;11:793-800. https://doi.org/10.4161/cbt.11.9.15045
  59. Kneissl J, Keller S, Lorber T, Heindl S, Keller G, Drexler I, et al. Association of amphiregulin with the cetuximab sensitivity of gastric cancer cell lines. Int J Oncol 2012;41:733-744. https://doi.org/10.3892/ijo.2012.1479
  60. Chen CT, Kim H, Liska D, Gao S, Christensen JG, Weiser MR. MET activation mediates resistance to lapatinib inhibition of HER2-amplified gastric cancer cells. Mol Cancer Ther 2012;11:660-669. https://doi.org/10.1158/1535-7163.MCT-11-0754

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