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Relationship of HER2 with age, gender, location of the tumor, and tumor budding in colorectal adenocarcinoma at H. Adam Malik General Hospital, Medan, Indonesia

  • Adi Muradi Muhar ,
  • Lidya Imelda Laksmi ,
  • Nova Sabrina Lubis ,


Link of Video Abstract:


Background: Colorectal carcinoma is one of the most common malignancies and is one of the leading causes of cancer-related death worldwide. The incidence of colorectal carcinoma in Indonesia is reported to be 12.8 per 100,000 adult population, accounting for 9.5% of all cancer-related deaths. Assessment of Human Epidermal Growth Factor Receptor 2 (HER2) expression is used to help predict tumor behavior and the effect of anti-HER2 receptor therapy. This study aims to analyze the relationship between HER2 immunohistochemical expression with age, gender, tumor location, and tumor budding in this malignancy.

Methods: This study is a cross sectional analytic study of 45 samples diagnosed with colorectal carcinoma at H. Adam Malik General Hospital Medan. Tumor budding was assessed for tumor invasiveness based on the International Tumor Budding Consensus Conference (ITBCC) 2016 in a field area of ​​0.785 mm2 with a 20x objective lens using a three-level scoring system, which was categorized into low budding (0-4 buds), intermediate budding (5-9 buds), and high budding (≥10 buds). Staining was performed using immunohistochemistry of the monoclonal anti-human HER2 anti-human DBS manufacturer, which would appear positive on the tumor cell membrane at a dilution of 1:100. HER2 expression was assessed using the HERACLES criteria. The results are presented as a score of 0, 1+, 2+, 3+, then categorized into negative (score 0-2+) and positive (score 3+). Data were analyzed using SPSS version 25.0 for Windows.

Results: There was no significant relationship between HER2 and clinicopathological parameters such as age (p=0.755), gender (p>0.05) and tumor location (p>0.05). However, there was a significant relationship between HER2 and tumor budding histopathological parameters with a value of p=0.011 in a positive direction (the greater the number of budding, the more positive HER2 expression, and vice versa).

Conclusion: HER2 is not significantly related to age, gender and tumor location. However, it is significantly associated with tumor budding. HER2 plays a role in the proliferation and differentiation of colorectal carcinoma tumor cells.


  1. GLOBOCAN 2020-Global Cancer Observatory-IARC:World Health Organizationfile. 2020. [Available at:] [Accessed on: 1st August 2023].
  2. National Cancer Management Committee of the Ministry of Health of the Republic of Indonesia. National Guidelines for Medical Services for the Management of Colorectal Cancer. 2017. [Available at:] [Accessed on: 1st August 2023].
  3. Nagtegaal ID, Arends MJ, Salto-Tellez M. Colorectal adenocarcinoma. In WHO Classification of Tumors: Digestive System Tumors. 5th WHO Classification of Tumors Editorial Board (Ed), International Agency for Research on Cancer. Lyon. 2019:177-87
  4. Kim BH, Kim JM, Kang GH, Chang HJ, Kang DW, Kim JH, et al. Standardized Pathology Report for Colorectal Cancer, 2nd Edition. Journal of Pathology and Translational Medicine 2020;54(1):1-19.
  5. Lugli A, Kirsch R, Ajioka YO, Bosman F, Cathomas G, Dawson H, et al. Recommendations for Reporting Tumor Budding in Colorectal Cancer Based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Modern Pathology. 2017;30(9):1299-1311.
  6. Wyk HC, Park J, Roxburgh C. The Role of Tumor Budding in Predicting Survival in Patients with Primary Operable Colorectal Cancer: A Systematic Review. Cancer Treat Rev. 2015;41(2):151-159.
  7. De Smedt L, Palmans S, Sagaert X. Tumor budding in colorectal cancer: what do we know and what can we do? Virchows Arch. 2016;468(1):397-408.
  8. Rogers AC, Winter DC, Heeney A. Systematic Review and Meta-Analysis of The Impact of Tumor Budding in Colorectal Cancer. Brother J Cancer. 2016;115(7):831-840.
  9. Koelzer VH, Zlobec I, Lugli A. Tumor budding in colorectal cancer, ready for diagnostic practice? Hum Pathol. 2016;47(1):4-19.
  10. Rogers AC, Gibbons D, Hanley AM. Prognostic Significance of Tumor Budding in Rectal Cancer Biopsies Before Neoadjuvant Therapy. Pathol mod. 2014;27(1):156-162.
  11. Zlobec I, Hadrich M, Dawson H. Intratumoural Budding (ITB) in Preoperative Biopsies Predicts The Presence of Lymph Node and Distant Metastases in Colon and Rectal Cancer Patients. Brother J Cancer. 2014;110(4):1008-1013.
  12. Kilicarslan A, Dogan HT, Sungu N, Dogan M, Yalcin A, Dede DS, et al. Association Between Her2/Neu Status In Colorectal Carcinoma and Clinicopathological Features: A Retrospective Study Using Whole – Tissue Sections. Pol J Pathol. 2018;69(2):143-149.
  13. Madani SH, Sadeghi E, Rezaee A, Sadeghi M, Khazaee S, Amirifard N, et al. Survey of HER2-neu Expression in Colonic Adenocarcinoma in the West of Iran. Asian Pacific Journal of Cancer Prevention. 2015;16(17):7671-7674.
  14. Wang XY, Zheng ZX, Sun Y, Bai YH, Shi YF, Zhou LX, et al. Significance Of HER2 Protein Expression And HER2 Gene Amplification In Colorectal Adenocarcinomas. World J Gastrointest Oncol. 2019;11(4):335-347.
  15. Razzaq EA, Venkatachalam T, Bajbouj K, Rahmani M, Mahdami A, Rawat S, et al. Her2 Overexpression Is A Putative Diagnostic And Prognostic Biomarker For Late-Stage Colorectal Cancer In North African Patients. Libyan Journal Of Medicine. 2021;16(1):1955462.
  16. Thrumurthy SG, Thrumurthy SS, Gilbert CE, Ross P, Haji A. Colorectal adenocarcinoma: risks, prevention and diagnosis. BMJ. 2016;354:i3590.
  17. Park SH, Song CW, Kim YB, Kim YS, Chun HR, Lee JH, et al. Clinicopathological Characteristics of Colon Cancer Diagnosed at Primary Health Care Institutions. Intest Res. 2014;12(2):131-138.
  18. Lugito NP. Clinical characteristics of young Indonesian colorectal cancer patients: A preliminary study. Medicinus. 2016;5(3):1- 3.
  19. Goldblum Jr. Large bowel. Goldblum JR, Lamps LW, McKenney JK, Myers JL Rosai and Ackerman's Surgical Pathology Eleventh Edition. Elsevier. 2018:1810-1915.
  20. Li CY, Song B, Wang YY, Meng H, Guo SB, Liu LN, et al. Age at menarche and risk of colorectal cancer: A meta-analysis. PlOS ONE. 2013;8(6):65645.
  21. Tu J, Yu Y, Liu W, Chen S. Significance of Human Epidermal Growth Factor Receptor 2 Expression In Colorectal Cancer. Experimental and Therapeutic Medicine. 2015;9(1):17-24.
  22. Yang WJ, Shen XJ, Ma XX, Tan ZG, Song Y, Guo YT, et al. Correlation of Human Epidermal Growth Factor Receptor Protein Expression and Colorectal Cancer. World J Gastroenterol. 2015;21(28):8687-8696.
  23. Ni S, Wang X, Chang J, Sun H, Weng W, Wang X, et al.Human Epidermal Growth Factor Receptor 2Overexpression And Amplification In Patients With Colorectal Cancer: A Large-Scale Retrospective Study In Chinese Population. Front. Oncol. 2022;12(1):842787.
  24. Ozer SP, Barut SG, Ozer B, Catal O, Sit M. The relationship between tumor budding and survival in colorectal carcinomas. Revista da Associação Médica Brasileira. 2019;65(12):1442-1447.
  25. Denis JA, Lacorte JM. Detection of RAS mutations in circulating tumor cells: applications in colorectal cancer and prospects. Détection des mutations RAS dans les cellules tumorales circulantes : applications au cancer colorectal et perspectives. Ann Biol Clin (Paris). 2017;75(6):607-618.
  26. Bosch SL, Teerenstra S, de Wilt JH. Predicting Lymph Node Metastasis in pT1 Colorectal Cancer: A Systematic Review of Risk Factors Providing Rationale for Therapy Decisions. endoscopy. 2013;45(10):827-834.
  27. Lestari AAW, Prabawa IPY, Wiranata S, Supadmanaba IGP. High eosinophils lymphocyte ratio (ELR) related with subtype of breast cancer in Sanglah General Hospital, Bali. Annals of Oncology. 2018;29:ix11-ix12.
  28. Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007;26(45):6469-6487.

How to Cite

Muhar, A. M., Laksmi, L. I., & Lubis, N. S. (2023). Relationship of HER2 with age, gender, location of the tumor, and tumor budding in colorectal adenocarcinoma at H. Adam Malik General Hospital, Medan, Indonesia. Bali Medical Journal, 12(3), 3187–3191.




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Adi Muradi Muhar
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Lidya Imelda Laksmi
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Nova Sabrina Lubis
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