Prognostic significance of the wnt signalling pathway molecules APC, β-catenin and E-cadherin in colorectal cancer—a tissue microarray-based analysis
Version of Record online: 28 FEB 2007
Volume 50, Issue 4, pages 453–464, March 2007
How to Cite
Lugli, A., Zlobec, I., Minoo, P., Baker, K., Tornillo, L., Terracciano, L. and Jass, J. R. (2007), Prognostic significance of the wnt signalling pathway molecules APC, β-catenin and E-cadherin in colorectal cancer—a tissue microarray-based analysis. Histopathology, 50: 453–464. doi: 10.1111/j.1365-2559.2007.02620.x
- Issue online: 28 FEB 2007
- Version of Record online: 28 FEB 2007
- Date of submission 13 March 2006 Accepted for publication 8 June 2006
- colorectal cancer;
- tissue microarray;
- wnt signalling pathway
Aims: To investigate dysregulation of the wnt signalling pathway by assessing β-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 β-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 β-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 β-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 β-catenin expression and loss of membranous E-cadherin are independent, adverse prognostic factors in MMR-proficient and MLH1– CRC.