EXPRESSION PATTERNS AND CLINICAL SIGNIFICANCE OF ESTROGEN RECEPTOR, PROGESTERONE RECEPTOR, AND HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2/neu IN GALLBLADDER CANCER

Authors

  • Deepti Mishra Department of Pathology & Cancer Genetics, Kalyan Singh Super Specialty Cancer Institute, Lucknow, U.P., India
  • Akhilesh Krishna Department of Pathology & Cancer Genetics, Kalyan Singh Super Specialty Cancer Institute, Lucknow, U.P., India
  • Priyanka Sameer Department of Pathology & Cancer Genetics, Kalyan Singh Super Specialty Cancer Institute, Lucknow, U.P., India
  • Shreshtha Ghosh Department of Pathology & Cancer Genetics, Kalyan Singh Super Specialty Cancer Institute, Lucknow, U.P., India
  • Durgesh Kumar Department of Surgical Oncology, Kalyan Singh Super Speciality Cancer Institute, Lucknow, U.P., India
  • Ankur Verma Department of Surgical Oncology, Kalyan Singh Super Speciality Cancer Institute, Lucknow, U.P., India

DOI:

https://doi.org/10.15407/exp-oncology.2026.02.139

Keywords:

gallbladder cancer, estrogen receptor, progesterone receptor, HER2/neu, estrogen receptor beta

Abstract

Background. Gallbladder carcinoma (GBC) is a rare cancer. However, it is the most common malignancy of the biliary tract system and ranks as the sixth most common malignancy of the digestive tract. It occurs primarily in females, and previous reports indicate that the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2/neu (HER2/neu) play significant roles in GBC. However, reported findings remain inconsistent. This study aimed to determine the expression status of ERα, ERβ, PR, and HER2/neu in GBC and to investigate their associations with clinicopathological features of patients. Materials and Methods. 55 GBC patients were included in the study. The expression levels of ERα, ERβ, PR, and HER2/neu proteins were evaluated using immunohistochemistry method. Results. ERα expression was absent in all cases, while PR and HER2/neu positivity were observed in 5.5% and 18.2% cases, respectively. Of total, 34 (61.8%) cases showed positive expression of ERβ. Compared with adjacent normal tissues, ERβ mean positivity was higher in GBC tissues. Significant associations were found between ERβ expression and tumor differentiation and gallstones (p < 0.05). Predominant expression of ERβ was observed in GBC of stages II and III. Conclusion. ERβ was frequently expressed in GBC and significantly associated with tumor differentiation, suggesting its potential role in progression of GBC.

References

Guo H, Zhang D, Li Z, et al. Global burden of gallbladder cancer in 2022 and predictions to 2042. Dig Liver Dis. 2025;57(6):1294-1300. https://doi.org/10.1016/j.heliyon.2023.e17488

Vuthaluru S, Sharma P, Chowdhury S, et al. Global epidemiological trends and variations in the burden of gallbladder cancer. J Surg Oncol. 2023;128(6):980-988. https://doi.org/10.1002/jso.27450

Mathur P, Sathishkumar K, Chaturvedi M, et al. ICMR-NCDIR-NCRP Investigator Group. Cancer Statistics, 2020: Report from National Cancer Registry Programme, India. JCO Glob Oncol. 2020; 6:1063-1075. https://doi.org/10.1200/GO.20.00122

Perez-Moreno P, Riquelme I, Garcia P, et al. Environmental and lifestyle risk factors in the carcinogenesis of gallbladder cancer. J Pers Med. 2022;12(2):234. https://doi.org/10.3390/jpm12020234

Etminan M, Delaney JA, Bressler B, et al. Oral contraceptives and the risk of gallbladder disease: A comparative safety study. CMAJ. 2011;183(8):899-904. https://doi.org/10.1503/cmaj.110161

Mhatre S, Lacey B, Sherliker P, et al. Reproductive factors and gall-bladder cancer, and the effect of common genetic variants on these associations: A case-control study in India. Int J Epidemiol. 2022;51(3):789-798. https://doi.org/10.1093/ije/dyab197

Gupta P, Agarwal A, Gupta V, et al. Expression and clinicopathological significance of estrogen and progesterone receptors in gallbladder cancer. Gastrointest Cancer Res. 2012;5(2):41-47. https://pmc.ncbi.nlm.nih.gov/articles/PMC3369597/

Saranga BR, Singh R, Gupta R, et al. Female sex hormone receptors in gallbladder cancer. J Gastrointest Cancer. 2015;46(2):143-148. https://doi.org/10.1007/s12029-015-9698-z

Vikash, Johri N, Aswal P, et al. Expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu in gallbladder carcinoma in North Indian population. Natl J Physiol Pharm Pharmacol. 2023;13(1):90-95. https://doi.org/10.5455/njppp.2023.13.05250202207062022

Hryciuk B, Pęksa R, Bienkowski M, et al. Expression of female sex hormone receptors, connective tissue growth factor and HER2 in gallbladder cancer. Sci Rep. 2020;10(1):1871. https://doi.org/10.1038/s41598-020-58777-y

Roa I, de Toro G, Schalper K, et al. Overexpression of the HER2/neu gene: A new therapeutic possibility for patients with advanced gallbladder cancer. Gastrointest Cancer Res. 2014;7(2):42-48. PMID: 24799970

Bhagat TS, Gulati G, Bhagat R, et al. Epidemiology of gallbladder cancer in India 2018-2023. Santosh Univ J Health Sci. 2024;10:87-92. https://doi.org/10.4103/sujhs.sujhs_12_24

Gupta V, Chandra A, Kumar S, et al. Does gallbladder cancer behave differently in young patients? J Clin Oncol. 2014;32(15):e15097. https://doi.org/10.1200/jco.2014.32.15_suppl.e1509

Gupta S, Kori C, Kumar V, et al. Epidemiological study of gallbladder cancer patients from North Indian Gangetic planes–A high-volume centre’s experience. J Gastrointest Cancer. 2016;47(1):27-35. https://doi.org/10.1007/s12029-015-9781-5

Dutta U, Bush N, Kalsi D, et al. Epidemiology of gallbladder cancer in India. Chin Clin Oncol. 2019;8(4):33. https://doi.org/10.21037/cco.2019.08.03

Shukla PJ, Barreto SG, Gupta P, et al. Is there a role for estrogen and progesterone receptors in gall bladder cancer? HPB (Oxford). 2007;9(4):285-288. https://doi.org/10.1080/13651820701481489

Mani R, Gupta A, Gupta S, et al. Expression of ER, PR, and HER2/Neu and correlation with tumor markers in gall bladder carcinoma. J Can Res Ther. 2023;19(5):12791287. https://doi.org/10.4103/jcrt.jcrt_1754_21

Toledo C, Matus CE, Barraza X, et al. Expression of HER2 and bradykinin B1 receptors in precursor lesions of gallbladder carcinoma. World J Gastroenterol. 2012;18(11):1208-1215. https://doi.org/10.4103/jcrt.jcrt_1754_21

Chaube A, Tewari M, Garbyal RS, et al. Preliminary study of p53 and c-erbB-2 expression in gallbladder cancer in Indian patients. BMC Cancer. 2006;6:126. https://doi.org/10.1186/1471-2407-6-126

Ashai F, Ashraf A, Rashid A, et al. Expression of Her2/neu receptor in carcinoma gallbladder correlates significantly with advanced tumor stage. Int J Hepatobiliary Pancreat Dis. 2015;5:86-91. https://doi.org/10.5348/ijhpd-2015-40-CR-15

Park JS, Jung WH, Kim JK, et al. Estrogen receptor alpha, estrogen receptor beta, and progesterone receptor as possible prognostic factor in radically resected gallbladder carcinoma. J Surg Res. 2009;152(1):104-110. https://doi.org/10.1016/j.jss.2008.01.032

Submitted: February 21, 2026

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Published

21.08.2026

How to Cite

Mishra, D., Krishna, A., Sameer, P., Ghosh, S., Kumar, D., & Verma, A. (2026). EXPRESSION PATTERNS AND CLINICAL SIGNIFICANCE OF ESTROGEN RECEPTOR, PROGESTERONE RECEPTOR, AND HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2/neu IN GALLBLADDER CANCER. Experimental Oncology, 48(2), 139–145. https://doi.org/10.15407/exp-oncology.2026.02.139

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