PMID- 32353192 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20231104 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 25 IP - 10 DP - 2020 Oct TI - HER2 Overexpression as a Poor Prognostic Determinant in Resected Biliary Tract Cancer. PG - 886-893 LID - 10.1634/theoncologist.2019-0922 [doi] AB - 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. CI - (c) AlphaMed Press 2020. FAU - Vivaldi, Caterina AU - Vivaldi C AUID- ORCID: 0000-0001-9307-2326 AD - Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Fornaro, Lorenzo AU - Fornaro L AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Ugolini, Clara AU - Ugolini C AD - Department of Laboratory Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Niccoli, Cristina AU - Niccoli C AD - Department of Laboratory Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Musettini, Gianna AU - Musettini G AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Pecora, Irene AU - Pecora I AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Cacciato Insilla, Andrea AU - Cacciato Insilla A AD - Department of Surgical, Medical, Molecular Pathology and Critical Area, Division of Pathology, University of Pisa, Pisa, Italy. FAU - Salani, Francesca AU - Salani F AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Pasquini, Giulia AU - Pasquini G AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Catanese, Silvia AU - Catanese S AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Lencioni, Monica AU - Lencioni M AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Masi, Gianluca AU - Masi G AD - Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Campani, Daniela AU - Campani D AD - Department of Surgical, Medical, Molecular Pathology and Critical Area, Division of Pathology, University of Pisa, Pisa, Italy. FAU - Fontantini, Gabriella AU - Fontantini G AD - Department of Surgical, Medical, Molecular Pathology and Critical Area, Division of Pathology, University of Pisa, Pisa, Italy. FAU - Falcone, Alfredo AU - Falcone A AD - Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Vasile, Enrico AU - Vasile E AD - Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. LA - eng PT - Journal Article DEP - 20200511 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM CIN - Oncologist. 2020 Nov;25(11):e1818. PMID: 32715579 CIN - Oncologist. 2020 Nov;25(11):e1819. PMID: 32969114 CIN - Oncologist. 2021 Oct;26(10):e1893-e1894. PMID: 34176184 CIN - Oncologist. 2021 Oct;26(10):e1895-e1896. PMID: 34176190 MH - *Biliary Tract Neoplasms/genetics/surgery MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Neoplasm Recurrence, Local/genetics MH - Neoplasm Staging MH - Prognosis MH - Receptor, ErbB-2/genetics MH - Retrospective Studies PMC - PMC7543291 OTO - NOTNLM OT - Biliary tract cancer OT - Cholangiocarcinoma OT - Gallbladder cancer OT - HER2 OT - Prognosis COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2020/05/01 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/10/01 CRDT- 2020/05/01 06:00 PHST- 2019/12/02 00:00 [received] PHST- 2020/04/01 00:00 [accepted] PHST- 2020/05/01 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/05/01 06:00 [entrez] PHST- 2020/10/01 00:00 [pmc-release] AID - ONCO13349 [pii] AID - 10.1634/theoncologist.2019-0922 [doi] PST - ppublish SO - Oncologist. 2020 Oct;25(10):886-893. doi: 10.1634/theoncologist.2019-0922. Epub 2020 May 11.