Open AccessHER2 Overexpression as a Poor Prognostic Determinant in Resected Biliary Tract Cancer
Author(s) -
Vivaldi Caterina,
Fornaro Lorenzo,
Ugolini Clara,
Niccoli Cristina,
Musettini Gianna,
Pecora Irene,
Cacciato Insilla Andrea,
Salani Francesca,
Pasquini Giulia,
Catanese Silvia,
Lencioni Monica,
Masi Gianluca,
Campani Daniela,
Fontantini Gabriella,
Falcone Alfredo,
Vasile Enrico
Publication year - 2020
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2019-0922
Subject(s) - medicine , immunohistochemistry , hazard ratio , confidence interval , oncology , stage (stratigraphy) , fluorescence in situ hybridization , biomarker , cancer , gastroenterology , pathology , gene , paleontology , biochemistry , chromosome , biology , chemistry
Background HER2 overexpression has been investigated as a potential biomarker and therapeutic target in biliary tract cancer (BTC), but a prognostic role of such alteration has not been demonstrated yet. Materials and Methods We retrospectively evaluated HER2 protein expression by immunohistochemistry (IHC) in 100 patients with radically resected BTC. HER2 gene amplification was assessed by fluorescence in situ hybridization (FISH) in 2+ and 3+ cases at IHC. High HER2 protein expression was defined as either IHC 3+ or 2+ associated with FISH positivity. The primary objective of the study was to evaluate the prognostic role of HER2 overexpression in terms of disease‐free survival (DFS) and overall survival (OS). Secondary endpoints were the prevalence of HER2 overexpression and the possible correlation with other clinicopathological features. Results HER2 overexpression was identified in 11 patients and was not related to other clinicopathological factors. DFS was significantly shorter in HER2‐positive compared with HER2‐negative patients (10.6 vs. 20.9 months, log‐rank p = .017). HER2 confirmed its prognostic value for DFS at multivariate analysis (hazard ratio 2.512; 95% confidence interval, 1.232–5.125; p = .011) together with nodal stage ( p < .001), resection margin ( p = .027), and tumor site ( p = .030). There was no difference in OS between HER2‐positive and ‐negative patients ( p = .068). Conclusion HER2 overexpression represents an independent prognostic factor for disease recurrence in patients with BTC treated with potentially curative surgery. Implications for Practice HER2 overexpression may play an independent role in promoting an aggressive behavior in resectable biliary tract cancer. This evidence could be helpful in improving prognostic stratification after resection and, primarily, should endorse the rationale to investigate HER2 as a therapeutic target in biliary tract cancer.