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

被引:126
作者
Kim, Min A. [1 ]
Lee, Hye Seung [2 ]
Lee, Hee Eun [2 ]
Kim, Ji Hun [1 ]
Yang, Han-Kwang [3 ,4 ]
Kim, Woo Ho [1 ,3 ]
机构
[1] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110799, South Korea
[2] Seoul Natl Univ, Bundang Hosp, Dept Pathol, Gyeonggi, South Korea
[3] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110799, South Korea
[4] Seoul Natl Univ, Coll Med, Dept Surg, Seoul 110799, South Korea
关键词
epithelial-mesenchymal transition; immunohistochemistry; stomach neoplasms; survival analysis; tissue array analysis; E-CADHERIN; TUMOR PROGRESSION; PROMOTER METHYLATION; DOWN-REGULATION; BETA-CATENIN; CELL-LINES; CANCER; SNAIL; METASTASIS; PLASTICITY;
D O I
10.1111/j.1365-2559.2009.03247.x
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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.
引用
收藏
页码:442 / 451
页数:10
相关论文
共 32 条
[1]
Slug is overexpressed in gastric carcinomas and may act synergistically with SIPI and Snail in the down-regulation of E-cadherin [J].
Alves, C. Castro ;
Rosivatz, E. ;
Schott, C. ;
Hollweck, R. ;
Becker, I. ;
Sarbia, M. ;
Carneiro, F. ;
Becker, K-F .
JOURNAL OF PATHOLOGY, 2007, 211 (05) :507-515
[2]
Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors [J].
Baumgart, Egbert ;
Cohen, Michael S. ;
Neto, Brasil Silva ;
Jacobs, Micah A. ;
Wotkowicz, Chad ;
Rieger-Christ, Kimberly M. ;
Biolo, Andreia ;
Zeheb, Ron ;
Loda, Massimo ;
Libertino, John A. ;
Summerhayes, Ian C. .
CLINICAL CANCER RESEARCH, 2007, 13 (06) :1685-1694
[3]
Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment [J].
Brabletz, T ;
Jung, A ;
Reu, S ;
Porzner, M ;
Hlubek, F ;
Kunz-Schughart, LA ;
Knuechel, R ;
Kirchner, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (18) :10356-10361
[4]
Opinion - Migrating cancer stem cells - an integrated concept of malignant tumour progression [J].
Brabletz, T ;
Jung, A ;
Spaderna, S ;
Hlubek, F ;
Kirchner, T .
NATURE REVIEWS CANCER, 2005, 5 (09) :744-749
[5]
Bukholm IK, 2000, J PATHOL, V190, P15
[6]
Cell adhesion and signalling by cadherins and Ig-CAMs in cancer [J].
Cavallaro, U ;
Christofori, G .
NATURE REVIEWS CANCER, 2004, 4 (02) :118-132
[7]
Molecular aspects of epithelial cell plasticity: implications for local tumor invasion and metastasis [J].
Gotzmann, J ;
Mario, M ;
Eger, A ;
Schulte-Hermann, R ;
Foisner, R ;
Beug, H ;
Mikulits, W .
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 2004, 566 (01) :9-20
[8]
Gastric cancer [J].
Hohenberger, P ;
Gretschel, S .
LANCET, 2003, 362 (9380) :305-315
[9]
Expression profiling of epithelial plasticity in tumor progression [J].
Jechlinger, M ;
Grunert, S ;
Tamir, IH ;
Janda, E ;
Lüdemann, S ;
Waerner, T ;
Seither, P ;
Weith, A ;
Beug, H ;
Kraut, N .
ONCOGENE, 2003, 22 (46) :7155-7169
[10]
Cancer statistics, 2003 [J].
Jemal, A ;
Murray, T ;
Samuels, A ;
Ghafoor, A ;
Ward, E ;
Thun, MJ .
CA-A CANCER JOURNAL FOR CLINICIANS, 2003, 53 (01) :5-26