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


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.
Lugli
A
A
Department of Pathology, McGill University, Montreal, Canada.
Zlobec
I
I
Minoo
P
P
Baker
K
K
Tornillo
L
L
Terracciano
L
L
Jass
J R
JR
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein / Q000096:biosynthesis / Q000502:physiology*; D015820:Cadherins / Q000096:biosynthesis / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D012044:Regression Analysis; D015398:Signal Transduction; D046888:Tissue Array Analysis; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000096:biosynthesis / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D000070957:MutL Protein Homolog 1