HER2 gene (ERBB2) amplification is a rare event in non-liver-fluke associated cholangiocarcinogenesis
Posted on 2019-12-06 - 04:46
Abstract Background Cholangiocarcinoma is a rapidly fatal cancer entity with a median survival of less than one year. In contrast to many other malignancies, no substantial therapeutic breakthrough has been made in the past few decades, thereby limiting the treatment to cytotoxic chemotherapy with little beneficial effect for most patients. Targeted therapy tailored to the individual has shown substantial success in the recent past as a promising avenue for cancer therapy. Methods In this study, we determined the frequency of amplification of the HER2 gene in a comprehensive and well-characterized European cholangiocarcinoma cohort encompassing 436 patients including intrahepatic (n = 155), proximal (n = 155) and distal (n = 126) cholangiocarcinoma by strict application of a combined immunohistochemical and in situ hybridization algorithm following the current guidelines for HER2 assessment in gastric cancer. Results We identified a proportion of 1.4% (n = 6) patients that demonstrated HER2 gene amplification, with the highest rate among the distal cholangiocarcinoma patients (2.4%). None of the patients with equivocal (2+) immunohistochemical staining results exhibited gene amplification molecularly. In four of the five patients with HER2 positivity, gene amplification was already present in concomitantly tested high-grade biliary intraepithelial neoplasia (80%). HER2 gene amplification was not significantly associated with other clinical parameters, including survival. Conclusions This study identifies HER2 gene amplification as a rare event in cholangiocarcinoma of the Western population, occurring already in high-grade BilIN in a subset of patients. Furthermore, we provide a robust testing algorithm that may be used prior to therapy administration in future clinical trials evaluating the role of HER2 as a predictive marker in cholangiocarcinoma.
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Albrecht, Thomas; Rausch, Melina; Rössler, Stephanie; Albrecht, Michael; Braun, Jana; Geissler, Veronika; et al. (2019). HER2 gene (ERBB2) amplification is a rare event in non-liver-fluke associated cholangiocarcinogenesis. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4772462.v1
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AUTHORS (18)
TA
Thomas Albrecht
MR
Melina Rausch
SR
Stephanie Rössler
MA
Michael Albrecht
JB
Jana Braun
VG
Veronika Geissler
AM
Arianeb Mehrabi
MV
Monika Vogel
AP
Anita Pathil-Warth
GM
Gunhild Mechtersheimer
MR
Marcus Renner
CR
Christian Rupp
KW
Karl Weiss
EB
Elena Busch
BK
Bruno Köhler
CS
Christoph Springfeld
PS
Peter Schirmacher
BG
Benjamin Goeppert