The intratumoral distribution of nuclear beta-catenin is a prognostic marker in colon cancer.
BACKGROUND
Most colon cancers harbor mutations of APC or beta-catenin, both of which may lead to nuclear beta-catenin accumulation in the tumor cells and constitutively activated expression of its target genes. In many colon cancers, however, nuclear beta-catenin accumulation is heterogeneous throughout the tumor and often confined to the tumor margin. Herein, the authors investigated whether the intratumoral distribution of nuclear beta-catenin can serve as a prognostic marker for survival and tumor progression of stage IIA colon cancer patients.


METHODS
In total, 142 patients with primarily resected, moderately differentiated stage IIA colon cancer were included in this study. The patterning of nuclear beta-catenin expression was evaluated on immunohistochemically stained whole tissue sections of the tumors and was correlated with cancer-specific survival and disease-free survival using univariate and multivariate statistical analyses.


RESULTS
Four distinct patterns of nuclear beta-catenin expression were identified, and 2 main categories comprising tumors with or without intratumoral regulation of nuclear beta-catenin were distinguished. Moreover, the results demonstrated that the patterning, and especially the regulation or absence of regulation of nuclear beta-catenin expression, was a strong predictive marker of patient survival and tumor progression.


CONCLUSIONS
The current results indicated that the distribution of nuclear beta-catenin expression can be used as a good prognostic marker in patients with stage IIA colon cancer. Thus, the evaluation of nuclear beta-catenin may help to identify patients who will have a shorter than average survival and patients with a greater risk of disease progression who may be considered for adjuvant therapeutic modalities and intensified clinical aftercare in the future.
Horst
David
D
Pathologisches Institut der Ludwig-Maximilians-Universität, Munich, Germany. david.horst@med.uni-muenchen.de
Reu
Simone
S
Kriegl
Lydia
L
Engel
Jutta
J
Kirchner
Thomas
T
Jung
Andreas
A
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000401:mortality; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051176:beta Catenin / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051176:beta Catenin