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

Histopathology. 2009 Mar;54(4):442-51. doi: 10.1111/j.1365-2559.2009.03247.x.

Abstract

Aims: 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).

Methods and results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / metabolism
  • Catenins / metabolism
  • Epithelium / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Keratins / metabolism
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Mesoderm / pathology
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Prognosis
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / metabolism
  • Snail Family Transcription Factors
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • Tissue Array Analysis
  • Transcription Factors / metabolism
  • Vimentin / metabolism

Substances

  • Cadherins
  • Catenins
  • Neoplasm Proteins
  • S100 Calcium-Binding Protein A4
  • S100 Proteins
  • Snail Family Transcription Factors
  • Transcription Factors
  • Vimentin
  • S100A4 protein, human
  • Keratins
  • MMP2 protein, human
  • Matrix Metalloproteinase 2