Prognostic significance of the wnt signalling pathway molecules APC, beta-catenin and E-cadherin in colorectal cancer: a tissue microarray-based analysis

Histopathology. 2007 Mar;50(4):453-64. doi: 10.1111/j.1365-2559.2007.02620.x.


Aims: To investigate dysregulation of the wnt signalling pathway by assessing beta-catenin expression/increasing expression and loss of cytoplasmic adenomatous polyposis coli (APC) and membranous E-cadherin in colorectal cancer (CRC) and determining the prognostic significance of these variables.

Methods and results: Unselected, non-consecutive CRC resections (n = 1420) were subdivided into three groups: mismatch repair (MMR)-proficient, MLH1- and presumed hereditary non-polyposis colonic cancer (HNPCC). Immunohistochemical analysis of beta-catenin expression (0% versus > 0%) and increasing expression (increasing percentage-positivity) and loss of APC and E-cadherin was performed using the tissue microarray technique. In MMR-proficient CRC, increased nuclear beta-catenin expression and loss of membranous E-cadherin were independently associated with higher N stage (P = 0.03 and < 0.0001), vascular invasion (P < 0.01 and < 0.001) and worse survival (P < 0.01 and < 0.001). Additionally, there was an association between loss of membranous E-cadherin and higher T stage (P = 0.03). In MLH1- CRC, loss of membranous E-cadherin was associated with higher N stage (P = 0.05) and worse survival (P = 0.03). In presumed HNPCC CRC nuclear beta-catenin and membranous E-cadherin were not associated with tumour progression or worse survival. In all CRC subsets loss of cytoplasmic APC was not associated with clinicopathological features.

Conclusions: Increasing nuclear beta-catenin expression and loss of membranous E-cadherin are independent, adverse prognostic factors in MMR-proficient and MLH1- CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenomatous Polyposis Coli Protein / biosynthesis
  • Adenomatous Polyposis Coli Protein / physiology*
  • Cadherins / biosynthesis
  • Cadherins / physiology*
  • Carrier Proteins / genetics
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / metabolism
  • Cytoplasm / metabolism
  • DNA Mismatch Repair
  • Female
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • MutL Protein Homolog 1
  • Nuclear Proteins / genetics
  • Prognosis
  • Regression Analysis
  • Signal Transduction
  • Tissue Array Analysis
  • Wnt Proteins / physiology*
  • beta Catenin / biosynthesis
  • beta Catenin / physiology*


  • Adaptor Proteins, Signal Transducing
  • Adenomatous Polyposis Coli Protein
  • Cadherins
  • Carrier Proteins
  • MLH1 protein, human
  • Nuclear Proteins
  • Wnt Proteins
  • beta Catenin
  • MutL Protein Homolog 1