MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis.
OBJECTIVE
Overexpression of MUC1 and cytosolic interaction of the mucin with beta-catenin are claimed to be involved in colorectal carcinogenesis. In vitro data published recently suggest that MUC1 overexpression results in an increase of steady state levels of nuclear beta-catenin. We tried to elucidate the coexpression of both molecules in colorectal cancer to demonstrate possible correlations with clinical, pathological, and prognostic data.


METHODS
An immunohistochemical double staining study was performed to characterize the expression and subcellular distribution of MUC1 and beta-catenin in a series of 205 patients with colorectal carcinoma. The results were correlated with clinicopathological variables as well as overall survival.


RESULTS
MUC1 was strongly expressed in the tumor center and at the invasion front in approximately 50% of the cases. Similar results were obtained with regard to nuclear accumulation of beta-catenin at the invasive tumor parts. MUC1 protein expression in the tumor center correlated significantly with a low grade of differentiation, and nuclear beta-catenin in the tumor periphery was more frequent in carcinomas of the left colon and rectum. Overexpression of MUC1 and beta-catenin, as well as their nuclear coexpression at the invasion front correlated with a worse overall survival in an univariate analysis. However, only pathological tumor-node-metastasis staging and MUC1 at the invasion front revealed as independent prognostic factors.


CONCLUSIONS
These results suggest that MUC1 and beta-catenin are coexpressed at the invasion front of colorectal carcinomas and that this feature is associated with an accelerated course of disease and worse prognosis.
Baldus
Stephan E
SE
Institute of Pathology, University of Cologne, Cologne, Germany. s-e.baldus@uni-koeln.de
Mönig
Stefan P
SP
Huxel
Sandra
S
Landsberg
Stephanie
S
Hanisch
Franz-Georg
FG
Engelmann
Katja
K
Schneider
Paul M
PM
Thiele
Jürgen
J
Hölscher
Arnulf H
AH
Dienes
Hans P
HP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis*; D016896:Treatment Outcome; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D018396:Mucin-1; D015534:Trans-Activators; D051176:beta Catenin