Altered distribution of beta-catenin and prognostic roles in colorectal carcinogenesis.
OBJECTIVE
Although beta-catenin cytoplasmic stabilization and nuclear translocation play a key role in initiation of colorectal cancer (CRC), the mechanisms are far from clear. The aim of this study was to investigate the relation of expressions of cyclooxygenase (COX)-2 and E-cadherin, and the beta-catenin gene exon 3 mutation to the altered distribution of beta-catenin, and their roles in CRC progression and prognosis.


METHODS
Expressions of beta-catenin, COX-2 and E-cadherin in 96 tissue specimens were detected by immunohistochemistry, and mutation of beta-catenin gene exon 3 was screened by polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC).


RESULTS
Cytoplasmic/nuclear expression of beta-catenin and reduced membranous expression of E-cadherin were associated, respectively, with the earlier and later stages of sequential colorectal carcinogenesis (p<0.05). The altered distribution of beta-catenin was significantly associated with both high Dukes' stages and poor differentiation of CRC (p<0.05). It also had a parallel relationship with COX-2 overexpression (p<0.05, Spearman's rank analysis), but not with reduced E-cadherin expression. Kaplan-Meier analysis showed a significantly worse survival rate for CRC patients with altered expression of beta-catenin (p<0.05, log-rank test). Nevertheless, we failed to find any exon 3 mutation of beta-catenin gene in all 60 cases of CRC.


CONCLUSIONS
Altered distribution of beta-catenin occurs in the early stage of colorectal carcinogenesis and has a parallel relationship with COX-2 overexpression. It may serve as a potential marker for the progression and prognosis of CRC. The exon 3 mutation did not appear contributive to the abnormal expression of beta-catenin in CRCs in a Chinese population.
Chen
Senqing
S
Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
Liu
Juying
J
Li
Guimei
G
Mo
Fugen
F
Xu
Xinyu
X
Zhang
Tong
T
Zhang
Xiaomei
X
Li
Jintian
J
Han
Xiao
X
Sun
Yujie
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D015996:Survival Rate; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D015820:Cadherins; D051176:beta Catenin; D051546:Cyclooxygenase 2