Correlation of aPKC-iota and E-cadherin expression with invasion and prognosis of cholangiocarcinoma.
BACKGROUND
The abnormal expression of atypical protein kinase C-iota (aPKC-iota) subtype and E-cadherin play important roles in tumor occurrence and progression. This study was designed to investigate the correlation of expression of aPKC-iota and E-cadherin with the clinicopathological characteristics and prognosis of cholangiocarcinoma, and to analyze the molecular mechanisms of invasion and metastasis of the tumor.


METHODS
EnVision immunohistochemistry was used to detect the expression of aPKC-iota and E-cadherin in 9 specimens of benign bile duct tissues, 35 specimens of cholangiocarcinoma and 6 specimens of metastatic cholangiocarcinoma. The relationship of the expression with clinicopathological characteristics, invasion and prognosis of cholangiocarcinoma was analyzed. A multivariate regression analysis was made of these data by the Cox proportional hazard model.


RESULTS
The positive expression level of aPKC-iota in cholangiocarcinoma was remarkably higher than that in benign bile duct tissues (68.6% vs. 11.1%, P=0.006), but the expression level of E-cadherin was lower in cholangiocarcinoma than in benign bile duct tissues (37.1% vs. 88.9%, P=0.016). Correlation analysis revealed that the expression of aPKC-iota was positively related to tumor differentiation and invasion, whereas that of E-cadherin was entirely the contrary. Moreover, there was a negative relationship between the expression of aPKC-iota and that of E-cadherin (r=-0.287, P<0.05). Univariate analysis showed that the overall survival rate of the group with a higher expression of aPKC-iota in cholangiocarcinoma was remarkably lower than that of the group with a lower expression (P<0.01); multivariate analysis revealed that the expressions of aPKC-iota and E-cadherin are important prognostic factors for cholangiocarcinoma (P<0.05).


CONCLUSIONS
The expressions of aPKC-iota and E-cadherin may reflect the differentiation and invasive potential of cholangiocarcinoma. aPKC-iota and E-cadherin may be independent prognostic factors and, when used in combination with clinicopathological characteristics, may increase the accuracy in predicting the prognosis of patients with cholangiocarcinoma. As a polar regulative associated protein, aPKC-iota may play an important role in the invasion and metastasis of cholangiocarcinoma.
Li
Qiang
Q
Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wang
Jian-Ming
JM
Liu
Cong
C
Xiao
Bao-Lai
BL
Lu
Jin-Xi
JX
Zou
Sheng-Quan
SQ
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D016764:Cell Polarity; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D011493:Protein Kinase C / Q000378:metabolism*; D000099293:Protein Kinase C-lambda
D015820:Cadherins; D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda