Tissue microarray analysis of beta-catenin in colorectal cancer shows nuclear phospho-beta-catenin is associated with a better prognosis.
OBJECTIVE
Beta-catenin is involved in homotypic cell-cell adhesion and the wnt signaling pathway. Deregulation of beta-catenin levels, caused in part by mutations of the adenomatous polyposis coli gene, is thought to play a role in the development of colorectal and other cancers. To further elucidate their roles, the expression pattern of beta-catenin and phosphospecific beta-catenin was correlated with clinical outcome in a series of patients with colorectal cancer.


METHODS
Immunohistochemical analysis of a tissue microarray with 650 colorectal cancer specimens was performed to study the expression and subcellular localization of beta-catenin and phosphospecific beta-catenin. These results were correlated with other clinicopathological factors and with overall survival.


RESULTS
The majority of cancers retained some degree of beta-catenin membranous staining, whereas cytoplasmic or nuclear expression was seen in 42.5% and 20.4% of specimens, respectively. Phospho-beta-catenin showed nuclear staining in 9.5% of specimens, and there was no apparent membranous or cytoplasmic staining. There was no significant association between beta-catenin or phospho-beta-catenin and grade or stage. However, there was a positive correlation between beta-catenin and phospho-beta-catenin (P = 0.039), with phospho-beta-catenin representing a subset of nuclear beta-catenin. Patients with nuclear expression of beta-catenin did not have an altered survival compared with those that did not (P = 0.5611). Nuclear expression of phospho-beta-catenin, however, was associated with an improved survival (P = 0.0006). In multivariate analysis, only stage and phospho-beta-catenin were independently predictive of overall survival (P < 0.001 and P = 0.0034, respectively).


CONCLUSIONS
These findings support a role for beta-catenin overexpression in colorectal tumorigenesis and provide initial evidence that phospho-beta-catenin may be a marker for improved overall survival independent of stage and grade.
Chung
G G
GG
Department of Internal Medicine, Section Medical Oncology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510, USA.
Provost
E
E
Kielhorn
E P
EP
Charette
L A
LA
Smith
B L
BL
Rimm
D L
DL
D000818:Animals; D015820:Cadherins / Q000032:analysis; D002460:Cell Line; D002467:Cell Nucleus / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D003593:Cytoplasm / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000032:analysis; D015203:Reproducibility of Results; D015996:Survival Rate; D015534:Trans-Activators; D014162:Transfection; D016896:Treatment Outcome; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D051176:beta Catenin