L1 cell adhesion molecule is a novel independent poor prognostic factor of extrahepatic cholangiocarcinoma.
OBJECTIVE
Cholangiocarcinomas (CC) are associated with poor survival, but diagnostic markers and therapeutic targets have not yet been elucidated. We previously found aberrant expression of L1 cell adhesion molecule in intrahepatic CC and a role for L1 in the progression of intrahepatic CC. Here, we analyzed L1 expression in extrahepatic CC (ECC) and evaluated its prognostic significance.


METHODS
We examined L1 expression in tumors from 75 ECC patients by immunohistochemistry. We analyzed the correlations between L1 expression and clinicopathologic factors as well as patient survival.


RESULTS
L1 was not expressed in normal extrahepatic bile duct epithelium but was aberrantly expressed in 42.7% of ECC tumors. High expression of L1 was detected at the invasive front of tumors and was significantly associated with perineural invasion (P < 0.01). Univariate analysis indicated that various prognostic factors such as histologic grade 3, advanced pathologic T stage and clinical stage, perineural invasion, nodal metastasis, and high expression of L1 were risk factors predicting patient survival. Multivariate analyses done by Cox's proportional hazards model showed that high expression of L1 (hazard ratio, 2.171; 95% confidence interval, 1.162-4.055; P = 0.015) and nodal metastasis (hazard ratio, 2.088; 95% confidence interval, 1.159-3.764; P = 0.014) were independent risk factors for patient death.


CONCLUSIONS
L1 was highly expressed in 42.7% of ECC and its expression was significantly associated with perineural invasion. High expression of L1 and nodal metastasis were independent poor prognostic factors predicting overall survival in patients with ECC.
Li
Shengjin
S
Department of Pathology and Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon, Korea.
Jo
Young Suk
YS
Lee
Jae-Hyek
JH
Min
Jeong-Ki
JK
Lee
Eung Seuk
ES
Park
Taewoo
T
Kim
Jin-Man
JM
Hong
Hyo Jeong
HJ
D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
D039842:Neural Cell Adhesion Molecule L1