Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer.
OBJECTIVE
Recent in vitro studies showed that beta-catenin translocated into the tumor cell nucleus functions as an oncogene by transactivating oncogenes, including MMP-7. We conducted a large-scale analysis of beta-catenin and MMP-7 expression in human colon cancer to determine the potential clinical importance of these molecules.


METHODS
In 202 colon cancer patients with known postoperative outcomes, we determined the expression of beta-catenin and MMP-7 in the tumors immunohistochemically and correlated the findings with the patients' clinicopathological characteristics and survival.


RESULTS
We found 2 distinct patterns of beta-catenin nuclear accumulation (NA) in the colon cancers: diffuse NA (NAd) in 89 cases (44%) and selective NA at the invasion front (NAinv) in 18 cases (9%). The presence of the NAinv pattern was significantly correlated with advanced Dukes' stage (P = 0.0187) and tumor recurrence (P = 0.0005) as well as with MMP-7 expression in the tumor invasion front (P = 0.0025), resulting in extremely unfavorable clinical outcomes. A multivariate analysis determined that the NAinv expression pattern and Dukes' C stage were independent prognostic factors.


CONCLUSIONS
Oncogenic activation of beta-catenin in the tumor invasion front, as represented by its NAinv pattern of expression, may be an independent and reliable indicator of membership in a subset of colon cancer patients who are highly susceptible to tumor recurrence and have a less favorable survival rate.
Ougolkov
Andrei V
AV
Division of Diagnostic Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
Yamashita
Kaname
K
Mai
Masayoshi
M
Minamoto
Toshinari
T
D000328:Adult; D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D020783:Matrix Metalloproteinase 7