PREVALENCE OF HUMAN EPIDERMAL GROWTH FACTOR II IN GASTROESOPHAGEAL AND GASTRIC ADENOCARCINOMA (A Multi-center study)

Document Type : Original Article

Authors

Departement of Clinical Oncology Cairo University

Abstract

Metastatic Gastric cancer (GC) is a prevalent disease with a median overall survival (OS) between 32-37 weeks. Targeting human epidermal growth transmembrane factor receptor 2 (HER-2) has a predictive however controversial prognostic impact. This study was conducted to reveal the incidence of HER2 status in Egyptian and Yemeni GC patients. we aimed evaluating the association between different factors and HER2 overexpression. Moreover, the factors affecting (OS) and Progression-free survival (PFS) were assessed in HER2 positive cases. Methods: This is a Multi-center retrospective study. Gastric or gastro-esophageal junction carcinoma cases were collected. Epidemiological, clinicopathological and treatment data were analyzed. The HER2 status was assessed. Survival analysis was calculated and the determinants affecting it were analyzed. Results: out of 62 patients diagnosed with GC,10 patients had HER-2 +ve disease.50 % had metastatic disease. brain metastasis (3.3%) was presented in HER2-positive cases only, while bone (10%) and peritoneal metastasis (46.7%) were presented in HER2-negative cases only. The median survival was 25 months.HER-2 -ve and HER-2 +ve subgroups were 25 and 28 months respectively (P=0.68).the median (PFS) for entire group was 12 months and for HER-2 -ve vs HER-2 +ve cases ,it was 9 months in both groups(P=0.73). conclusion: the (HER2) rate in our cohort was 16.1% . The current study has highlighted the possible association between HER2-positivity and brain metastasis in gastric cancer patients and could confirm the higher incidence of liver metastasis and absence of peritoneal metastasis in those HER2 positive patients.

Keywords

Main Subjects

References

  1. References:
  1. Sung, Hyuna, Jacques Ferlay, Rebecca L. Siegel, Mathieu Laversanne, Isabelle Soerjomataram, Ahmedin Jemal, and Freddie Bray. 2021. “Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.” CA: A Cancer Journal for Clinicians 71 (3): 209–49. https:// org/10.3322/caac.21660
  2. Amal S Ibrahim , Hussein M Khaled , Nabiel NH Mikhail , Hoda Baraka , Hossam Kamel . Cancer Incidence in Egypt: Results of the National Population-Based Cancer Registry Program. https:// doi.org/10.1155/2014/437971
  3. M M Moasser, “The Oncogene HER2: Its Signaling and Transforming Functions and Its Role in Human Cancer Pathogenesis.https:// doi: 10.1038/sj.onc.1210477
  4. Cutsem, E. van, Y. Kang, H. Chung, L. Shen, A. Sawaki, F. Lordick, J. Hill, M. Lehle, A. Feyereislova, and Y. Bang. 2009. “Efficacy Results from the ToGA Trial: A Phase III Study of Trastuzumab Added to Standard Chemotherapy (CT) in First-Line Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer (GC).” https://doi.org/10.1200/jco.2009.27.18_suppl.lba4509
  5. Shitara, Kohei, Yung-Jue Bang, Satoru Iwasa, Naotoshi Sugimoto, Min-Hee Ryu, Daisuke Sakai, Hyun-Cheol Chung, et al. 2020. “Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer.” New England Journal of Medicine 382 (25): 2419–30. https:// DOI: 10.1056/NEJMoa2004413
  6. Jørgensen, Jan Trøst, and Maria Hersom. 2012. “HER2 as a Prognostic Marker in Gastric Cancer - A Systematic Analysis of Data from the Literature.” Journal of Cancer 3 (1): 137–44. doi:10.7150/jca.4090
  7. Dang, Hai Zhen, Yang Yu, and Shun Chang Jiao. 2012. “Prognosis of HER2 Over-Expressing Gastric Cancer Patients with Liver Metastasis.” World Journal of Gastroenterology 18 (19): 2402–7. https://  doi: 10.3748/wjg.v18.i19.2402
  8. Boku, Narikazu. 2014. “HER2-Positive Gastric Cancer.” Gastric Cancer 17 (1): 1. https://doi.org/10.1007/S10120-013-0252-Z.
  9. Terashima, Masanori, Koji Kitada, Atsushi Ochiai, Wataru Ichikawa, Issei Kurahashi, Shinichi Sakuramoto, Hitoshi Katai, Takeshi Sano, Hiroshi Imamura, and Mitsuru Sasako. 2012b. “Impact of Expression of Human Epidermal Growth Factor Receptors EGFR and ERBB2 on Survival in Stage II/III Gastric Cancer.” Clinical Cancer Research : An Official Journal of the American Association for Cancer Research 18 (21): 5992–6000. https:// doi: 10.1158/1078-0432.CCR-12-1318.
  10. Janjigian, Y. Y., D. Werner, C. Pauligk, K. Steinmetz, D. P. Kelsen, E. Jäger, H. M. Altmannsberger, et al. 2012a. “Prognosis of Metastatic Gastric and Gastroesophageal Junction Cancer by HER2 Status: A European and USA International Collaborative Analysis.” Annals of Oncology : Official Journal of the European Society for Medical Oncology 23 (10): 2656–62. https:// doi: 10.1093/annonc/mds104. Epub 2012 Jun 11.
  11. Gómez-Martin, Carlos, Elena Garralda, M. José Echarri, Anabel Ballesteros, Alberto Arcediano, José Luis Rodríguez-Peralto, Manuel Hidalgo, and Fernando López-Ríos. 2012. “HER2/Neu Testing for Anti-HER2-Based Therapies in Patients with Unresectable and/or Metastatic Gastric Cancer.” Journal of Clinical Pathology 65 (8): 751–57. https:// doi: 10.1136/jclinpath-2012-200774. Epub 2012 May 8
  12. Lei, Yu ying, Jin yu Huang, Qiong rui Zhao, Nan Jiang, Hui mian Xu, Zhen ning Wang, Hai qing Li, Shi bo Zhang, and Zhe Sun. 2017. “The Clinicopathological Parameters and Prognostic Significance of HER2 Expression in Gastric Cancer Patients: A Meta-Analysis of Literature.” World Journal of Surgical Oncology 15 (1): 1–7. https:// doi: 10.1186/s12957-017-1132-5
  13. Cutsem, Eric van, Yung Jue Y-j Yung-Jue Bang, Feng Feng-yi, Jian M. Xu, Keun Wook K-w Keun-Wook Lee, Shun-Chang S-c Shun Chang Jiao, Jorge León Chong, et al. 2015. “HER2 Screening Data from ToGA: Targeting HER2 in Gastric and Gastroesophageal Junction Cancer.” Gastric Cancer 18 (3): 476–84. https://doi.org/10.1007/s10120-014-0402-y
  14. Grabsch, Heike, Shivan Sivakumar, Sally Gray, Helmut E. Gabbert, and Wolfram Müller. 2010. “HER2 Expression in Gastric Cancer: Rare, Heterogeneous and of No Prognostic Value - Conclusions from 924 Cases of Two Independent Series.” Cellular Oncology : The Official Journal of the International Society for Cellular Oncology 32 (1–2): 57–65. https://doi.org/10.3233/CLO-2009-0497
  15. Gravalos, C., and A. Jimeno. 2008a. “HER2 in Gastric Cancer: A New Prognostic Factor and a Novel Therapeutic Target.” Annals of Oncology : Official Journal of the European Society for Medical Oncology 19 (9): 1523–29. doi: 10.1093/annonc/mdn169
  16. Ahmed Abdel-Salam, Ramy, Amira El-Hawary, Mie Ali Mohamed, and Tawakol Gamil. 2018. “Immunohistochemical Expression of Her2/Neu in Gastric Carcinomas in Egyptian Patients.” Journal of Clinical Pathology and Diagnosis. Vol. 1.No1:3 hhttps://www.researchgate.net/publication/333310268_immunohistochemical-expression-of-her2neu-in-gastric-carcinomas-in-egyptian-patients
  17. Abdel Hadi, Ahmed, Ali el Hindawi, Amal Hareedy, Heba Khalil, Ranya al Ashiry, Shady Elia, Ahmed Sadek, et al. 2016. “Her2/Neu Protein Expression and Oncogene Amplification in Gastric Carcinoma with Clinico-Pathological Correlation in Egyptian Patients.” Macedonian Journal of Medical Sciences 4 (4): 535–42.
  18. Ibarra, Julio A, and Lowell W Rogers. 2010. “Fixation Time Does Not Affect Expression of HER2/Neu A Pilot Study.” Am J Clin Pathol 134: 594–96.
  19. Yamashita-Kashima, Yoriko, Sei Shu, Keigo Yorozu, Kaoru Hashizume, Yoichiro Moriya, Kaori Fujimoto-Ouchi, and Naoki Harada. 2014. “Importance of Formalin Fixing Conditions for HER2 Testing in Gastric Cancer: Immunohistochemical Staining and Fluorescence in Situ Hybridization.” Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 17 (4): 638–47.
  20. Roy, Partha S., Tomar Nyodu, Munlima Hazarika, B. J. Saikia, C. Bhuyan, Amit Inamdar, C. W. Nyuthe, B. Borthakur, and J. D. Sharma. 2019. “Prevalence of HER2 Expression and Its Correlation with Clinicopathological Parameters in Gastric or Gastroesophageal Junction Adenocarcinoma in North-East Indian Population.” Asian Pacific Journal of Cancer Prevention : APJCP 20 (4): 1139. https:// doi: 10.31557/APJCP.2019.20.4.1139.
  21. Nadaf, Asmanaz Saleem, Hephzibah Rani, and Udipi Shastri Dinesh. 2018. “Immuno-Histochemical Assessment of HER2NEU Expression in Gastric Adenocarcinoma in North Karnataka, India.” Asian Pacific Journal of Cancer Prevention : APJCP 19 (5): 1381–85. https:// doi: 10.22034/APJCP.2018.19.5.1381
  22. Alvarado-Cabrero, Isabel, Sara Gil-Hernández, Ana Ruelas-Perea, Diego Villaverde-Rodríguez, José Roberto Montes-Ochoa, and Rafael Medrano-Guzmán. 2017. “Immunohistochemical Assessment of HER2 Expression in Gastric Cancer. A Clinicopathologic Study of 93 Cases.” Cirugía y Cirujanos (English Edition) 85 (6): 504–9. https://doi.org/10.1016/J.circir.2016.11.016
  23. Bermúdez, Ana, Isabel Arranz-Salas, Silvia Mercado, Juan A. López-Villodres, Virginia González, Francisca Ríus, María V. Ortega, Carmen Alba, Isabel Hierro, and Diego Bermúdez. 2021. “Her2-Positive and Microsatellite Instability Status in Gastric Cancer—Clinicopathological Implications.” Diagnostics 11 (6).
  24. Dai, Xiaomin, Xijiong Zhang, and Jin Yu. 2019. “Clinicopathological Features and Borrmann Classification Associated with HER2-Positive in Primary Gastric Cancer.” Clinical and Experimental Gastroenterology 12: 287.
  25. Kataoka, Yoshiki, Hiroshi Okabe, Akihiko Yoshizawa, Sachiko Minamiguchi, Kenichi Yoshimura, Hironori Haga, and Yoshiharu Sakai. 2013. “HER2 Expression and Its Clinicopathological Features in Resectable Gastric Cancer.” Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 16 (1): 84–93.
  26. Janjigian, Y. Y., D. Werner, C. Pauligk, K. Steinmetz, D. P. Kelsen, E. Jäger, H. M. Altmannsberger, et al. 2012b. “Prognosis of Metastatic Gastric and Gastroesophageal Junction Cancer by HER2 Status: A European and USA International Collaborative Analysis” 23 (10): 2656–62.
  27. Kurokawa, Yukinori, Nariaki Matsuura, Yutaka Kimura, Shinichi Adachi, Junya Fujita, Hiroshi Imamura, Kenji Kobayashi, et al. 2015. “Multicenter Large-Scale Study of Prognostic Impact of HER2 Expression in Patients with Resectable Gastric Cancer.” Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 18 (4): 691–97.
  28. Wang, Hong Bo, Xiao Feng Liao, and Jian Zhang. 2017. “Clinicopathological Factors Associated with HER2-Positive Gastric Cancer A Meta-Analysis.” Medicine (United States) 96 (44).
  29. Oono, Yasuhiro, Takeshi Kuwata, Kenji Takashima, Yusuke Yoda, Hiroaki Ikematsu, Kohei Shitara, Takahiro Kinoshita, and Tomonori Yano. “Clinicopathological Features and Endoscopic Findings of HER2-Positive Gastric Cancer.” Surgical Endoscopy 32 (9): 3964–71.
  30. Matsusaka, Satoshi, Atsushi Nashimoto, Kazuhiro Nishikawa, Akira Miki, Hiroto Miwa, Kazuya Yamaguchi, Takaki Yoshikawa, et al. 2016. “Clinicopathological Factors Associated with HER2 Status in Gastric Cancer: Results from a Prospective Multicenter Observational Cohort Study in a Japanese Population (JFMC44-1101).” Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 19 (3): 839–51. https://doi.org/10.1007/S10120-015-0518-8.
  31. Cavanna, Luigi, Pietro Seghini, Camilla di Nunzio, Elena Orlandi, Emanuele Michieletti, Elisa Maria Stroppa, Patrizia Mordenti, Chiara Citterio, Stefano Vecchia, and Adriano Zangrandi. 2018. “Gastric Cancer with Brain Metastasis and the Role of Human Epidermal Growth Factor 2 Status.” Oncology Letters 15 (4): 5787. https://doi.org/10.3892/ol.2018.8054
  32. Feilchenfeldt, J., Z. Varga, M. Siano, H. I. Grabsch, U. Held, B. Schuknecht, A. Trip, et al. 2015. “Brain Metastases in Gastro-Oesophageal Adenocarcinoma: Insights into the Role of the Human Epidermal Growth Factor Receptor 2 (HER2).” British Journal of Cancer 2015 113:5 113 (5): 716–21.
  33. Sung Son, Ho, Yeon Myung Shin, Kwang Kuk Park, Kyung Won Seo, Ki Young Yoon, Hee Kyung Jang, Sang-Ho Lee, Song I Yang, and Jeong Hoon Kim. 2014. “Correlation between HER2 Overexpression and Clinicopathological Characteristics in Gastric Cancer Patients Who Have Undergone Curative Resection.” J Gastric Cancer 14 (3): 180–86.
  34. Terashima, Masanori, Koji Kitada, Atsushi Ochiai, Wataru Ichikawa, Issei Kurahashi, Shinichi Sakuramoto, Hitoshi Katai, Takeshi Sano, Hiroshi Imamura, and Mitsuru Sasako. 2012a. “Impact of Expression of Human Epidermal Growth Factor Receptors EGFR and ERBB2 on Survival in Stage II/III Gastric Cancer.” Clinical Cancer Research : An Official Journal of the American Association for Cancer Research 18 (21): 5992–6000. https://doi.org/10.1158/1078-0432.CCR-12-1318
  35. Wang,” Human Epidermal Growth Factor Receptor 2 in Gastric Cancer: Evidence from a Meta-Anaysis.”,, L. He, and Y. Cheng. 2018. “An Independent Survival Prognostic Role Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 20 (2): 212–20.
Egyptian Journal of Medical Research
Volume 6, Issue 3
July 2025
Pages 206-224

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