HER Receptor Family: Novel Candidate for Targeted Therapy for Gallbladder and Extrahepatic Bile Duct Cancer.
OBJECTIVE
Biliary tract cancers (BTC) are uncommon in the United States, but are endemic in parts of South America and Asia. BTCs are aggressive tumors associated with poor survival. Activation of HER-2/neu (erbB2) and/or epidermal growth factor receptor (EGFR) are important in breast, colon, and lung cancers. Tumor specimens from patients from the United States and Chile were examined for expression of HER-2/neu, EGFR, and their activated forms (p-erbB2, p-EGFR).


METHODS
Specimens from 77 gallbladder cancers (GBC), 16 extrahepatic bile duct cancers (EHBDC), 21 intrahepatic bile duct cancers (IHBDC), 11 cases of cholecystitis (CHOLE), and 8 normal gallbladders (NGB) were examined for HER-2/neu, p-erbB2, EGFR, and p-EGFR expression by immunohistochemistry (IHC), with scores of 2+ or 3+ defined as positive. HER-2/neu gene amplification was analyzed by double color HER-2/neu gene/chromosome 17 centromere (CEP17) fluorescence in situ hybridization (FISH) assays


RESULTS
HER-2/neu-positive IHC staining was found in 31.2% of GBC, 31.3%, of EHBDC, and 33.3% of IHBDC; 12.5% of CHOLE specimens showed 2+ staining and the remaining CHOLE and NGB were negative. HER-2/neu gene amplification was detected in 20.9% of GBC, 21.4% of EHBDC, and none of IHBDC. There was a significant correlation between IHC 2+ and 3+ and gene amplification (P =.0001).


CONCLUSIONS
HER-2/neu amplification was identified in more than 20% of GB and EHBDC. There was strong correlation between HER-2/neu IHC and FISH positivity. These findings indicate a role for HER-2/neu in some subsets of BTC, and provide a rationale for study of HER-2/neu-directed therapies in this setting.
Kawamoto
Toru
T
Department of Gastrointestinal Medical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX.
Krishnamurthy
Savitri
S
Tarco
Emily
E
Trivedi
Smita
S
Wistuba
Ignacio I
II
Li
Donghui
D
Roa
Ivan
I
Roa
Juan C
JC
Thomas
Melanie B
MB