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

Authors


Jeremy R Jass MD, DSc, FRCPath, FRCPA, Department of Cellular Pathology, St Mark's Hospital, Watford Road, Harrow, Middlesex, HA1 3UJ, UK. e-mail: jeremy.jass@nwlh.nhs.uk

Abstract

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.

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