Skip to main content
Top

03-02-2025 | Gallbladder Cancer | Original Article

Human epidermal growth factor receptor-2/neu expression in gallbladder cancer is significantly associated with clinicopathological parameters and survival

Authors: Sashibhusan Dash, Prajna Anirvan, Sagarika Samantaray, Prafulla Kumar Swain, Prasant Kumar Parida, Niranjan Rout, Manoranjan Ranjit

Published in: Indian Journal of Gastroenterology

Login to get access

Abstract

Background

Anti-human epidermal growth factor receptor-2 (Her-2/neu) target therapy has substantially improved the disease outcome of patients with breast and gastric/gastroesophageal cancers characterized by Her-2/neu overexpression and/or amplification. Consequently, evaluating Her-2/neu expression in other cancers to predict response to Her-2/neu targeting agents emerges as a crucial approach. We aimed at investigating the positivity rate of this receptor in gallbladder cancer (GBC) and assess the relationship between Her-2/neu status, clinicopathological parameters and survival to identify patients who would benefit most from anti-Her-2/neu-targeted therapy. The Her-2/neu expression was correlated with clinicopathological parameters and survival of GBC cases.

Methods

Total 235 surgically resected and histopathologically proven primary GBC cases were collected over a five-year period from January 1, 2017, and December 31, 2020. Her-2/neu expression in these cases was analyzed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).

Results

Employing testing algorithms (IHC scoring based on gastric cancer criteria, followed by FISH in equivocal cases), Her-2/neu positivity was identified in 43 (18.29%) GBC cases and was significantly associated with grade I tumors, tumor stage > T2, perineural invasion, surgical margin positivity and advanced TNM stage. The mean survival time for Her-2/neu-positive cases was 14 months (SE, 1.1; 95%CI, 11.7–16.06), while it was 20 months (SE, 0.69; 95%CI, 18.1–20.9) for Her-2-negative cases (p < 0.001).

Conclusions

Her-2/neu is expressed in about one-fifth of GBC patients and is significantly associated with tumor behavior and patient survival. Utilizing novel targeted agents may hold the key to improving the prognosis of these patients.

Graphical abstract

Literature
2.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [published correction appears in CA Cancer J Clin. 2020;70(4):313]. CA Cancer J Clin. 2018; 68:394-424. https://doi.org/10.3322/caac.21492. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [published correction appears in CA Cancer J Clin. 2020;70(4):313]. CA Cancer J Clin. 2018; 68:394-424. https://​doi.​org/​10.​3322/​caac.​21492.​
7.
go back to reference Czink E, Heining C, Weber TF, et al. Dauerhafte Remission unterdualer HER2-Blockade mit Trastuzumab und PertuzumabbeimetastasiertemGallenblasenkarzinom [Durable remission under dual HER2 blockade with Trastuzumab and Pertuzumab in a patient with metastatic gallbladder cancer]. Z Gastroenterol. 2016;54:426–30. https://doi.org/10.1055/s-0042-103498.CrossRefPubMed Czink E, Heining C, Weber TF, et al. Dauerhafte Remission unterdualer HER2-Blockade mit Trastuzumab und PertuzumabbeimetastasiertemGallenblasenkarzinom [Durable remission under dual HER2 blockade with Trastuzumab and Pertuzumab in a patient with metastatic gallbladder cancer]. Z Gastroenterol. 2016;54:426–30. https://​doi.​org/​10.​1055/​s-0042-103498.CrossRefPubMed
14.
go back to reference Gupta S, Misra S, Kori C, Kumar V, Husain N. Study of growth factor receptors expression and their clinicopathological correlation in carcinoma gallbladder: Is it the way forward? J Clin Oncol. 2015 ;33(15_suppl):e15158–e15158. Gupta S, Misra S, Kori C, Kumar V, Husain N. Study of growth factor receptors expression and their clinicopathological correlation in carcinoma gallbladder: Is it the way forward? J Clin Oncol. 2015 ;33(15_suppl):e15158–e15158.
15.
go back to reference Pujani M, Makker I, Makker A, Jetley S, Goel MM, Jetley S. Expression of human epidermal growth factor receptor (her 2/neu) and proliferative marker ki-67: association with clinicopathological parameters in gallbladder carcinoma. Asian Pac J Cancer Prev. 2016;17:3903–9.PubMed Pujani M, Makker I, Makker A, Jetley S, Goel MM, Jetley S. Expression of human epidermal growth factor receptor (her 2/neu) and proliferative marker ki-67: association with clinicopathological parameters in gallbladder carcinoma. Asian Pac J Cancer Prev. 2016;17:3903–9.PubMed
22.
go back to reference Matsuyama S, Kitajima Y, Sumi K, Mori D, Satoh T, Miyazaki K. Gallbladder cancers rarely overexpress HER-2/neu, demonstrated by Hercep test. Oncol Rep. 2004;11:815–9.PubMed Matsuyama S, Kitajima Y, Sumi K, Mori D, Satoh T, Miyazaki K. Gallbladder cancers rarely overexpress HER-2/neu, demonstrated by Hercep test. Oncol Rep. 2004;11:815–9.PubMed
23.
go back to reference Nakazawa K, Dobashi Y, Suzuki S, et al. HER receptor family: novel candidate for targeted therapy for gallbladder and extrahepatic bile duct cancer. Gastrointest Cancer Res. 2007;1:221–7. Nakazawa K, Dobashi Y, Suzuki S, et al. HER receptor family: novel candidate for targeted therapy for gallbladder and extrahepatic bile duct cancer. Gastrointest Cancer Res. 2007;1:221–7.
24.
go back to reference Kawamoto T, Krishnamurthy S, Tarco E, et al. HER receptor family: novel candidate for targeted therapy for gallbladder and extrahepatic bile duct cancer. Gastrointest Cancer Res. 2007;1:221–7.PubMedPubMedCentral Kawamoto T, Krishnamurthy S, Tarco E, et al. HER receptor family: novel candidate for targeted therapy for gallbladder and extrahepatic bile duct cancer. Gastrointest Cancer Res. 2007;1:221–7.PubMedPubMedCentral
25.
go back to reference Harder J, Waiz O, Otto F, et al. Expression of HER2 and bradykinin B₁ receptors in precursor lesions of gallbladder carcinoma. World J Gastroenterol. 2012;18:1208–15.CrossRef Harder J, Waiz O, Otto F, et al. Expression of HER2 and bradykinin B₁ receptors in precursor lesions of gallbladder carcinoma. World J Gastroenterol. 2012;18:1208–15.CrossRef
27.
go back to reference Expression of epidermal growth factor receptor. p53, Bcl2, vascular endothelial growth factor, cyclooxygenase-2, cyclin D1, human epidermal receptor-2 and Ki-67: Association with clinicopathological profiles and outcomes in gallbladder carcinoma. J Carcinog. 2014;13:10. https://doi.org/10.4103/1477-3163.139450.CrossRef Expression of epidermal growth factor receptor. p53, Bcl2, vascular endothelial growth factor, cyclooxygenase-2, cyclin D1, human epidermal receptor-2 and Ki-67: Association with clinicopathological profiles and outcomes in gallbladder carcinoma. J Carcinog. 2014;13:10. https://​doi.​org/​10.​4103/​1477-3163.​139450.CrossRef
28.
go back to reference Roa I, de Toro G, Schalper K, de Aretxabala X, Churi C, Javle M. Overexpression of the HER2/neu gene: a new therapeutic possibility for patients with advanced gallbladder cancer. Gastrointest Cancer Res. 2014;7:42–8.PubMedPubMedCentral Roa I, de Toro G, Schalper K, de Aretxabala X, Churi C, Javle M. Overexpression of the HER2/neu gene: a new therapeutic possibility for patients with advanced gallbladder cancer. Gastrointest Cancer Res. 2014;7:42–8.PubMedPubMedCentral
39.
Metadata
Title
Human epidermal growth factor receptor-2/neu expression in gallbladder cancer is significantly associated with clinicopathological parameters and survival
Authors
Sashibhusan Dash
Prajna Anirvan
Sagarika Samantaray
Prafulla Kumar Swain
Prasant Kumar Parida
Niranjan Rout
Manoranjan Ranjit
Publication date
03-02-2025
Publisher
Springer India
Published in
Indian Journal of Gastroenterology
Print ISSN: 0254-8860
Electronic ISSN: 0975-0711
DOI
https://doi.org/10.1007/s12664-024-01723-x

Keynote series | Spotlight on menopause

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the systemic effects of menopause, so you can help patients in your clinics through the transition.   

Prof. Martha Hickey
Dr. Claudia Barth
Dr. Samar El Khoudary
Developed by: Springer Medicine
Watch now

Keynote webinar | Spotlight on adolescent vaping

Growing numbers of young people are using e-cigarettes, despite warnings of respiratory effects and addiction. How can doctors tackle the epidemic, and what health effects should you prepare to manage in your clinics?

Prof. Ann McNeill
Dr. Debbie Robson
Benji Horwell
Developed by: Springer Medicine
Watch now

Keynote webinar | Spotlight on modern management of frailty

Frailty has a significant impact on health and wellbeing, especially in older adults. Our experts explain the factors that contribute to the development of frailty and how you can manage the condition and reduce the risk of disability, dependency, and mortality in your patients.

Prof. Alfonso Cruz-Jentoft
Prof. Barbara C. van Munster
Prof. Mirko Petrovic
Developed by: Springer Medicine
Watch now

A quick guide to ECGs

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date. 

PD Dr. Carsten W. Israel
Developed by: Springer Medizin
Start the cases

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Read more