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. 2020 Oct;25(10):886-893.
doi: 10.1634/theoncologist.2019-0922. Epub 2020 May 11.

HER2 Overexpression as a Poor Prognostic Determinant in Resected Biliary Tract Cancer

Caterina Vivaldi  1   2 , Lorenzo Fornaro  2 , Clara Ugolini  3 , Cristina Niccoli  3 , Gianna Musettini  2 , Irene Pecora  2 , Andrea Cacciato Insilla  4 , Francesca Salani  2 , Giulia Pasquini  2 , Silvia Catanese  2 , Monica Lencioni  2 , Gianluca Masi  1   2 , Daniela Campani  4 , Gabriella Fontantini  4 , Alfredo Falcone  1   2 , Enrico Vasile  2
Affiliations

HER2 Overexpression as a Poor Prognostic Determinant in Resected Biliary Tract Cancer

Caterina Vivaldi et al. Oncologist. 2020 Oct.

Abstract

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.

Keywords: Biliary tract cancer; Cholangiocarcinoma; Gallbladder cancer; HER2; Prognosis.

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Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

Figures

Figure 1
Figure 1
Examples of HER2 immunohistochemistry (IHC) staining. IHC evaluation of HER2 in biliary tract cancer is scored as follows: score 3+ (A), score 2+ (B), score 1+ (C), score 0 (D).
Figure 2
Figure 2
Disease‐free survival curves according to HER2 status.
Figure 3
Figure 3
Overall survival curves according to HER2 status.
See this image and copyright information in PMC

Comment in

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