Expression of adhesion molecules and epithelial-mesenchymal transition factors in medullary carcinoma of the colorectum

Hum Pathol. 2015 Sep;46(9):1257-66. doi: 10.1016/j.humpath.2015.05.023. Epub 2015 Jun 10.

Abstract

Medullary carcinoma (MC) of the colorectum is known as a rare variant with favorable prognosis despite its poorly differentiated morphology. The mechanism of its favorable behavior has been unclear. Here, we compared the expressions of adhesion molecules and epithelial-mesenchymal transition (EMT)-related proteins in the central portion and invasive front between 43 MCs and 30 poorly differentiated adenocarcinomas (PDAs). The expressions of membranous E-cadherin (P < .0001), β-catenin (P < .0001) and claudin 1 (P = .0036) were significantly preserved in the invasive front of the MCs compared to those in the invasive front of the PDAs. E-cadherin membranous expression was also significantly preserved in the central portion of the MCs (P = .0178). Nuclear β-catenin expression in both the central portion (P = .0463) and invasive front (P = .0346) of the MCs was significantly less frequent compared to that in the PDAs. Snail (P = .0035) and Twist1 (P = .0463) expressions in the invasive front of the MCs were significantly less frequent compared to the PDAs, suggesting that the EMT phenomenon may occur rarely in colorectal MC. Reduced membranous E-cadherin expression in the MC central portion was significantly correlated with poor clinical outcome (P = .0086). Our immunohistochemical results indicate that preserved adhesion molecule protein and less frequent expression of EMT-related transcription factors in the invasive front contribute to the favorable prognosis of colorectal MCs. We suggest that a reduced expression of E-cadherin in the central portion might be a good biomarker for an unfavorable prognosis in cases of MC.

Keywords: Adhesion molecules; Colorectum; Epithelial-mesenchymal transition; Medullary carcinoma.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Medullary / chemistry*
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / mortality
  • Carcinoma, Medullary / pathology
  • Case-Control Studies
  • Cell Adhesion Molecules / analysis*
  • Cell Differentiation
  • Colorectal Neoplasms / chemistry*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Cell Adhesion Molecules