Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma

Epithelial-mesenchymal transition (EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers. The aim was to evaluate the expression of EMT-related proteins in gastric carcinoma (GC). The expression of nine EMT-related proteins in the GC tissues of 598 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of EMT-related proteins. Loss of epithelial protein and/or acquisition of the expression of mesenchymal proteins were observed in GC. These protein alterations were associated with diffuse type histology, advanced stage and poor patient outcome, respectively. Subjects were divided into three groups according to degree of EMT-related protein alteration. Increases in alteration of EMT-related protein were found to be significantly associated with poorly differentiated histology, higher pTNM stage and unfavourable outcome. Multivariate analysis showed that alterations in the expression of EMT-related proteins were independently associated with poor prognosis. Loss of epithelial proteins and/or the acquisition of mesenchymal proteins are associated with poorly differentiated histology, advanced stage and poor outcome in GC. The awareness and inhibition of EMT offer a promising target for prevention of metastatic progression and invasion.Lee HS, 2007, CLIN CANCER RES, V13, P4154, DOI 10.1158/1078-0432.CCR-07-0173Alves CC, 2007, J PATHOL, V211, P507, DOI 10.1002/path.2138Baumgart E, 2007, CLIN CANCER RES, V13, P1685, DOI 10.1158/1078-0432.CCR-06-2330Lascombe I, 2006, CLIN CANCER RES, V12, P2780, DOI 10.1158/1078-0432.CCR-05-2387Lee JM, 2006, J CELL BIOL, V172, P973Lombaerts M, 2006, BRIT J CANCER, V94, P661, DOI 10.1038/sj.bjc.6602996Willipinski-Stapelfeldt B, 2005, CLIN CANCER RES, V11, P8006, DOI 10.1158/1078-0432.CCR-05-0632Larue L, 2005, ONCOGENE, V24, P7443Moody SE, 2005, CANCER CELL, V8, P197, DOI 10.1016/j.ccr.2005.07.009Brabletz T, 2005, NAT REV CANCER, V5, P744, DOI 10.1038/nrc1694Tarin D, 2005, CANCER RES, V65, P5996Kim MA, 2004, HUM PATHOL, V35, P576, DOI 10.1016/j.humpath.2003.12.007Cavallaro U, 2004, NAT REV CANCER, V4, P118, DOI 10.1038/nrc1276Gotzmann J, 2004, MUTAT RES-REV MUTAT, V566, P9, DOI 10.1016/S1383-5742(03)00033-4Jechlinger M, 2003, ONCOGENE, V22, P7155, DOI 10.1038/sj.onc.1206887Hohenberger P, 2003, LANCET, V362, P305Xue CS, 2003, CANCER RES, V63, P3386Lee HS, 2003, J PATHOL, V200, P39, DOI 10.1002/path.1288Jemal A, 2003, CA-CANCER J CLIN, V53, P5Rosivatz E, 2002, AM J PATHOL, V161, P1881Thiery JP, 2002, NAT REV CANCER, V2, P442, DOI 10.1038/nrc822Van Aken E, 2001, VIRCHOWS ARCH, V439, P725, DOI 10.1007/S004280100516Brabletz T, 2001, P NATL ACAD SCI USA, V98, P10356Lang SH, 2001, BRIT J CANCER, V85, P590Machado JC, 2001, ONCOGENE, V20, P1525Rieger-Christ KM, 2001, HUM PATHOL, V32, P18, DOI 10.1053/hupa.2001.21140Yonemura Y, 2000, CLIN CANCER RES, V6, P4234Tomita K, 2000, CANCER RES, V60, P3650Bukholm IK, 2000, J PATHOL, V190, P15Machado JC, 1999, LAB INVEST, V79, P459NOMURA A, 1991, NEW ENGL J MED, V325, P1132JOOSSENS JV, 1981, NUTR CANCER, V2, P2501