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- DOI 10.18231/j.ijpo.2025.032
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Immunohistochemical expression of HER1, HER2, HER3 and HER4 in head and neck squamous cell carcinoma
Background: Lip, oral cavity cancers are ranked as the sixteenth most common cancer worldwide according to the latest GLOBOCAN estimates (2022). The determination of expression of ERBB receptors in head and neck squamous cell carcinoma (HNSCC) can help profile the patients, potentially devise newer treatment strategies and improve outcome for patients.
Aim and Objective: The aim was to study immunohistochemical expression of EGFR, HER2, HER3 and HER4 in HNSCC and association with clinical factors, prognostic factors and their co-expression.
Materials and Methods: 100 cases of head and neck squamous cell carcinoma were included in the study. Tumour representative blocks were selected for immunohistochemistry for EGFR, HER2, HER3 and HER4. IHC scoring was done using H-score. Results: In our study, 49% patients showed EGFR expression, 22% showed HER2 expression. HER2 expression showed association with lymph node involvement and extra nodal extension. 94% patients showed HER3 expression and 58% showed HER4 over expression. HER4 over expression showed correlation with sex of patient.
Conclusion: There is a need to conduct more such studies and clinical trials about expression of ERBB receptors in HNSCC as there are targeted drugs available against these receptors. Also, a reporting protocol needs to be established for interpreting immunohistochemical expression of these markers.
Keywords: Head and neck squamous cell carcinoma (HNSCC), Head and neck cancers (HNC), EGFR, HER2, HER3, HER4.
References
- Barsouk A, Aluru JS, Rawla P, Saginala K, Barsouk A. Epidemiology, risk factors, and prevention of head and neck squamous cell carcinoma. Med Sci. 2023;11(2):42.
- Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63.
- Gormley M, Creaney G, Schache A, Ingarfield K, Conway DI. Reviewing the epidemiology of head and neck cancer: definitions, trends and risk factors. Br Dent J. 2022;233(9):780–6.
- Bagal S, Budukh A, Thakur JS, Dora T, Qayyumi B, Khanna D, et al. Head and neck cancer burden in India: an analysis from published data of 37 population -based cancer registries. Ecancermedicalscience. 2023;17:1603.
- Williams HK. Molecular pathogenesis of oral squamous carcinoma. Mol Pathol. 2000;53(4):165–72.
- Todd R, Donoff RB, Wong DTW. The molecular biology of oral cancer: toward a tumour progression model. J Oral Maxillofac Surg. 1997;55(6):613–23.
- Xia W, Lau YK, Zhang HZ, Xiao FY, Johnston DA, Liu AR, et al. Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin Cancer Res. 1999;5(12):4164–74.
- Xu MJ, Johnson DE, Grandis JR. EGFR-targeted therapies in the post-genomic era. Cancer Metastasis Rev. 2017;36(3):463–73. Devi et al. / Indian Journal of Pathology and Oncology 2025;12(2):155–164 163
- Juergens RA, Bratman SV, Tsao MS, Laurie SA, Kuruvilla MS, Razak AR, Hansen AR. Biology and patterns of response to EGFR- inhibition in squamous cell cancers of the lung and head & neck. Cancer Treat Rev. 2017;54:43–57.
- Ulanovski D, Stern Y, Roizman P, Shpitzer T, Popovtzer A, Feinmesser R. Expression of EGFR and Cerb-B2 as prognostic factors in cancer of the tongue. Oral Oncol. 2004;40(5):532–7.
- Seifi S, Shafaei SN, Nosrati K, Ariaeifar B. Lack of elevated HER2/neu expression in epithelial dysplasia and oral squamous cell carcinoma in Iran. Asian Pac J Cancer Prev. 2009;10(4):661–4.
- Arteaga CL. Epidermal growth factor receptor dependence in human tumors: more than just expression?. Oncologist. 2002;7(S4):31–9.
- Kung JE, Jura N. Prospects for pharmacological targeting of pseudokinases. Nat Rev Drug Discov. 2019;18(7):501–26.
- Sergina NV, Rausch M, Wang D, Blair J, Hann B, Shokat KM, et al. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature. 2007;445(7126):437–41.
- Chiu CG, Masoudi H, Leung S, Voduc DK, Gilks B, Huntsman DG, et al. HER-3 overexpression is prognostic of reduced breast cancer survival: a study of 4046 patients. Ann Surg. 2010;251(6):1107–16.
- Bussu F, Ranelletti FO, Gessi M, Graziani C, Lanza P, Lauriola L, et al. Immunohistochemical expression patterns of the HER4 receptors in normal mucosa and in laryngeal squamous cell carcinomas: antioncogenic significance of the HER4 protein in laryngeal squamous cell carcinoma. Laryngoscope. 2012;122(8):1724–33.
- Silva SD, Alaoui-Jamali MA, Hier M, Soares FA, Graner E, Kowalski LP. Cooverexpression of ERBB1 and ERBB4 receptors predicts poor clinical outcome in pN+ oral squamous cell carcinoma with extranodal spread. Clin Exp Metastasis. 2014;31(3):307–16.
- McCarty Jr KS, Miller LS, Cox EB, Konrath JM, McCarty Sr KS. Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 1985;109(8):716–21.
- Laimer K, Spizzo G, Gastl G, Obrist P, Brunhuber T, Fong D, et al. High EGFR expression predicts poor prognosis in patients with squamous cell carcinoma of the oral cavity and oropharynx: a TMA- based immunohistochemical analysis. Oral Oncol. 2007;43(2):193–
- Hiraishi Y, Wada T, Nakatani K, Negoro K, Fujita S. Immunohistochemical expression of EGFR and p-EGFR in oral squamous cell carcinomas. Pathol Oncol Res. 2006;12(2):87–91.
- Sarkis SA, Abdullah BH, Abdul Majeed BA, Talabani NG. Immunohistochemical expression of epidermal growth factor receptor (EGFR) in oral squamous cell carcinoma in relation to proliferation, apoptosis, angiogenesis and lymphangiogenesis. Head Neck Oncol. 2010;2:1–8.
- Hashmi AA, Hussain ZF, Aijaz S, Irfan M, Khan EY, Naz S, et al. Immunohistochemical expression of epidermal growth factor receptor (EGFR) in South Asian head and neck squamous cell carcinoma: association with various risk factors and clinico- pathologic and prognostic parameters. World J Surg Oncol. 2018;16(1):1–9.
- Verma J, Dhingra V, Srivastava S, Misra V, Varma K, Singh S. Evaluation of epidermal growth factor receptor expression by a new scoring system in head and neck squamous cell carcinoma and its association with various pathological prognostic factors. J Oral Maxillofac Pathol. 2018;22(1):11–7.
- Mariezkurrena XA, Guimerá JA, Rodríguez JW, Weisman R, Ongkeko W. Immunohistochemistry study of EGFR expression in head and neck squamous cell carcinoma. Acta Otorrinolaringol Esp. 2005;56(4):143–6.
- Zafar M, Hashmi SN, Faisal MJ, Ahmed R, Ali SS. Immunohistochemical expression of epidermal growth factor receptor in head and neck squamous cell carcinoma. J Coll Physicians Surg Pak. 2017;27(4):209–12.
- Reimers N, Kasper HU, Weissenborn SJ, Stützer H, Preuss SF, Hoffmann TK, Speel EJ, et al. Combined analysis of HPV‐ DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer. Int J Cancer. 2007;120(8):1731–8.
- Glazer CA, Chang SS, Ha PK, Califano JA. Applying the molecular biology and epigenetics of head and neck cancer in everyday clinical practice. Oral Oncol. 2009;45(4-5):440–6.
- Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–78.
- Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116–27.
- Vermorken JB, Stöhlmacher-Williams J, Davidenko I, Licitra L, Winquist E, Villanueva C, et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013;14(8):697–
- Bernardes VF, Gleber-Netto FO, Sousa SF, Silva TA, Aguiar MC. Clinical significance of EGFR, Her-2 and EGF in oral squamous cell carcinoma: a case control study. J Exp Clin Cancer Res. 2010;29(1):1–7.
- Vats S, Ganesh MS, Agarwal A. Human epidermal growth factor receptor 2 neu expression in head and neck squamous cell cancers and its clinicopathological correlation: Results from an Indian cancer center. I Indian J Pathol Microbiol. 2018;61(3):313–8.
- Mirza S, Hadi N, Pervaiz S, Khan SZ, Mokeem SA, Abduljabbar T, et al. Expression of HER-2/neu in oral squamous cell carcinoma. Asian Pac J Cancer Prev. 2020;21(5):1465.
- Cavalot A, Martone T, Roggero N, Brondino G, Pagano M, Cortesina G. Prognostic impact of HER‐ 2/neu expression on squamous head and neck carcinomas. Head Neck. 2007;29(7):655–
- Khan AJ, King BL, Smith BD, Smith GL, DiGiovanna MP, Carter D, et al. Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma. Clin Cancer Res. 2002;8(2):540-8.
- Sardari Y, Pardis S, Tadbir AA, Ashraf MJ, Fattahi MJ, Ebrahimi H, et al. HER2/neu expression in head and neck squamous cell carcinoma patients is not significantly elevated. Asian Pac J Cancer Prev. 2012;13(6):2891-6.
- Pollock NI, Grandis JR. HER2 as a therapeutic target in head and neck squamous cell carcinoma. Clin Cancer Res. 2015;21(3):526–
- Gillison ML, Glisson BS, O’Leary E, Murphy BA, Levine MA, Kies MS, et al. Phase II trial of trastuzumab (T), paclitaxel (P) and cisplatin (C) in metastatic (M) or recurrent (R) head and neck squamous cell carcinoma (HNSCC): response by tumor EGFR and HER2/neu status. J Clin Oncol. 2006;24(18_suppl):5511.
- Erjala K, Sundvall M, Junttila TT, Zhang N, Savisalo M, Mali P, et al. Signaling via ErbB2 and ErbB3 associates with resistance and epidermal growth factor receptor (EGFR) amplification with sensitivity to EGFR inhibitor gefitinib in head and neck squamous cell carcinoma cells. Clin Cancer Res. 2006;12(13):4103–11.
- Chang CS, Shim JI, Byeon SJ, Lee EJ, Lee YY, Kim TJ, et al. Prognostic significance of HER3 expression in patients with cervical cancer. Cancers. 2022;14(9):2139.
- Takikita M, Xie R, Chung JY, Cho H, Ylaya K, Hong SM, et al. Membranous expression of Her3 is associated with a decreased survival in head and neck squamous cell carcinoma. J Transl Med. 2011;9:126.
- Wei Q, Sheng L, Shui Y, Hu Q, Nordgren H, Carlsson J. EGFR, HER2, and HER3 expression in laryngeal primary tumors and corresponding metastases. Ann Surg Oncol. 2008;15:1193-201.
- Deuss E, Gößwein D, Gül D, Zimmer S, Foersch S, Eger CS, et al. Growth factor receptor expression in oropharyngeal squamous cell cancer: her1–4 and c-met in conjunction with the clinical features and human papillomavirus (p16) status. Cancers. 2020;12(11):3358. 164 Devi et al. / Indian Journal of Pathology and Oncology 2025;12(2):155–164
- Li Q, Zhang R, Yan H, Zhao P, Wu L, Wang H, et al. Prognostic significance of HER3 in patients with malignant solid tumors. Oncotarget. 2017;8(40):67140.
- Tanner B, Hasenclever D, Stern K, Schormann W, Bezler M, Hermes M, et al. ErbB-3 predicts survival in ovarian cancer. J Clin Oncol. 2006;24(26):4317–23.
- Wei Q, Chen L, Sheng L, Nordgren H, Wester K, Carlsson J. EGFR, HER2 and HER3 expression in esophageal primary tumours and corresponding metastases. Int J Oncol. 2007;31(3):493–9.
- Hayashi M, Inokuchi M, Takagi Y, Yamada H, Kojima K, Kumagai J, et al. High expression of HER3 is associated with a decreased survival in gastric cancer. Clin Cancer Res. 2008;14(23):7843–9.
- Kountourakis P, Pavlakis K, Psyrri A, Rontogianni D, Xiros N, Patsouris E, et al. Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas. BMC Cancer. 2006;6:46.
- Sassen A, Rochon J, Wild P, Hartmann A, Hofstaedter F, Schwarz S, et al. Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients. Breast Cancer Res. 2008;10(1):R2.
- Wang Z, Goto Y, Allevato MM, Wu VH, Saddawi-Konefka R, Gilardi M, Alvarado D, et al. Disruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer. Nat Commun. 2021;12(1):2383.
- Zhang J, Saba NF, Chen GZ, Shin DM. Targeting HER (ERBB) signaling in head and neck cancer: An essential update. Mol Aspects Med. 2015;45:74-86.
- Jimeno A, Machiels JP, Wirth L, Specenier P, Seiwert TY, Mardjuadi F, et al. Phase Ib study of duligotuzumab (MEHD7945A) plus cisplatin/5‐ fluorouracil or carboplatin/paclitaxel for first‐ line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck. Cancer. 2016;122(24):3803–11.
- Fayette J, Wirth L, Oprean C, Udrea A, Jimeno A, Rischin D, et al. Randomized phase II study of duligotuzumab (MEHD7945A) vs. cetuximab in squamous cell carcinoma of the head and neck (MEHGAN Study). Front Oncol. 2016;6:232.
How to Cite This Article
Vancouver
Kinkhede D, Pangarkar M, Pagey RP, Sathawane P, Deulkar SA, Mahindra SR, Devi Y. Immunohistochemical expression of HER1, HER2, HER3 and HER4 in head and neck squamous cell carcinoma [Internet]. Indian J Pathol Oncol. 2025 [cited 2025 Oct 16];12(2):155-164. Available from: https://doi.org/10.18231/j.ijpo.2025.032
APA
Kinkhede, D., Pangarkar, M., Pagey, R. P., Sathawane, P., Deulkar, S. A., Mahindra, S. R., Devi, Y. (2025). Immunohistochemical expression of HER1, HER2, HER3 and HER4 in head and neck squamous cell carcinoma. Indian J Pathol Oncol, 12(2), 155-164. https://doi.org/10.18231/j.ijpo.2025.032
MLA
Kinkhede, Devika, Pangarkar, Meena, Pagey, Radhika Praveen, Sathawane, Prajakta, Deulkar, Shweta Ashok, Mahindra, Shraddha Rajan, Devi, Yogita. "Immunohistochemical expression of HER1, HER2, HER3 and HER4 in head and neck squamous cell carcinoma." Indian J Pathol Oncol, vol. 12, no. 2, 2025, pp. 155-164. https://doi.org/10.18231/j.ijpo.2025.032
Chicago
Kinkhede, D., Pangarkar, M., Pagey, R. P., Sathawane, P., Deulkar, S. A., Mahindra, S. R., Devi, Y.. "Immunohistochemical expression of HER1, HER2, HER3 and HER4 in head and neck squamous cell carcinoma." Indian J Pathol Oncol 12, no. 2 (2025): 155-164. https://doi.org/10.18231/j.ijpo.2025.032