γ-Catenin is an independent prognostic marker in early stage colorectal cancer.
OBJECTIVE
Expression and role of γ-catenin in colorectal carcinogenesis is not well understood. We aimed at characterizing γ-catenin's expression pattern during colorectal carcinogenesis.


METHODS
The expression pattern of γ-catenin was characterized in adenomas, primary colorectal carcinomas, and their corresponding metastases. Since this descriptive immunohistochemical analysis revealed upregulation of γ-catenin in the invasive front of both primary tumors and metastases, a tissue microarray (TMA) was performed, allowing for correlation of subcellular expression patterns with disease recurrence and cancer-specific survival. Comparison of γ-catenin expression with that of β-catenin was performed.


RESULTS
In normal colonic epithelium and adenomas, γ-catenin was weakly expressed at the membrane. In central areas of primary colorectal carcinomas, membranous and cytoplasmatic expression was present, with cytoplasmatic and nuclear upregulation of γ-catenin in the invasive fronts. Expression patterns found in metastases resembled those of their respective primary tumors. Subsequent TMA analysis showed that upregulation of cytoplasmatic γ-catenin in the invasive fronts of curatively resected early T2 and T3 colorectal carcinomas was associated with shortened disease-free survival and an increased risk of death (p=0.003; hazard ratio = 2.98; 95% confidence interval, 1.44-6.18).


CONCLUSIONS
The correlation of upregulated cellular γ-catenin levels with higher recurrences and impaired survival suggests a tumor promoting role of γ-catenin in colorectal cancer. γ-Catenin may therefore serve as a marker for identifying patients who are at increased risk of disease recurrence who may benefit from closer follow-up and adjuvant therapy.
Nagel
Jutta Maria
JM
Department of Medicine II, University of Munich, Marchioninistrasse 15, Munich, Germany.
Kriegl
Lydia
L
Horst
David
D
Engel
Jutta
J
Gautam
Shiva
S
Mantzoros
Christos S
CS
Kirchner
Thomas
T
Göke
Burkhard
B
Kolligs
Frank Thomas
FT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism; D003710:Demography; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D046888:Tissue Array Analysis; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism; D051185:gamma Catenin / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051176:beta Catenin; D051185:gamma Catenin