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Prognostic significance of the wnt signalling pathway molecules APC, β‐catenin and E‐cadherin in colorectal cancer—a tissue microarray‐based analysis
Author(s) -
Lugli A,
Zlobec I,
Minoo P,
Baker K,
Tornillo L,
Terracciano L,
Jass J R
Publication year - 2007
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2007.02620.x
Subject(s) - tissue microarray , mlh1 , adenomatous polyposis coli , colorectal cancer , cadherin , immunohistochemistry , catenin , wnt signaling pathway , cancer , beta catenin , microsatellite instability , cancer research , medicine , pathology , biology , oncology , dna mismatch repair , signal transduction , cell , gene , genetics , allele , microsatellite
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.