Gene amplification and protein overexpression of HER-2/neu in human extrahepatic cholangiocarcinoma as detected by chromogenic in situ hybridization and immunohistochemistry: its prognostic implication in node-positive patients.
BACKGROUND
In cholangiocarcinoma (CC), HER-2/neu protein overexpression has rarely been reported and the results are conflicting. The present study aimed to clarify the rates of HER-2/neu protein overexpression and gene amplification in human extrahepatic CC and to evaluate the correlation between HER-2/neu and several clinicopathologic features.


METHODS
We investigated HER-2 gene amplification by chromogenic in situ hybridization (CISH) and HER-2/neu protein overexpression by immunohistochemistry in 55 extrahepatic CC patients who underwent curative surgery at our institution.


RESULTS
Overexpression of HER-2/neu protein (staining intensity score > or = 2) was found in 16 out of 55 patients (29.1%). CISH revealed that HER-2 gene signals were increased in 10 out of 55 patients (18.1%). There was a positive and significant correlation between HER-2 gene amplification and HER-2/neu protein overexpression (Spearman's rho = 0.718, P < 0.01). In subgroup with lymph node metastases, HER-2 gene amplification by CISH was significant prognostic factor for survival (OR 43.6, 95% confidence interval 1.6-1219.6).


CONCLUSIONS
HER-2/neu protein overexpression by HER-2 gene amplification may occur in human extrahepatic CC and constitute an independent prognostic factor in patients with lymph node metastases. In subgroup with lymph node metastases who exhibit HER-2/neu overexpression might constitute potential candidates for new adjuvant therapy, such as humanized monoclonal antibodies.
Kim
H J
HJ
Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyukwan University School of Medicine, Pyung-Dong, Jongro-Ku, Seoul, South Korea. hongjoo3.kim@samsung.com
Yoo
T W
TW
Park
D I
DI
Park
J H
JH
Cho
Y K
YK
Sohn
C I
CI
Jeon
W K
WK
Kim
B I
BI
Kim
M K
MK
Chae
S W
SW
Sohn
J H
JH
D000368:Aged; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002863:Chromogenic Compounds; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
D002863:Chromogenic Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases