Document Type : Original Research


1 Department of Clinical and Anatomical Pathology, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Radiation Oncology, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran

3 Radiation Oncology Research Center, Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Oncosurgery, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran


Background & Objective: Iran is located in the esophageal cancer geographical belt. As multiple genetic alterations are responsible for the molecular pathogenesis of esophageal squamous cell cancer (ESCC), the role and frequency of HER2 expression, MMR deficiency, and PI3KCA mutation are not well defined.
Methods: We carried out HER2/neu expression, dMMR/MSI high, and PI3KCA mutation analysis in specimens of patients with ESCC. We accessed archival tissue blocks related to specimens of 68 ESCC cases at the time of surgery following neoadjuvant chemoradiation. These patients underwent surgery during 2013-2018 at the Cancer Institute of Iran affiliated with the Tehran University of Medical Sciences in Tehran.
Results: None of the patients showed HER2 expression, dMMR/MSI high, or PI3K mutations.
Conclusion: dMMR/MSI-H and PI3KCA mutation and HER2 expression may not be reliable andfrequent targets for systemic therapy in patients with esophageal SCC.


Main Subjects

  1. Bray FF, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal AJ. Erratum: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca Cancer J Clin. 2020;70(4):313. [DOI:10.3322/caac.21492] [PMID]
  2. Khademi H, Kamangar F. Esophageal cancer incidence trends in northeastern Iran: comparing rates over 36 years. 2012;15(4):194-5.
  3. Kmet J, Mahboubi E. Mechanized Information Storage, Retrieval and Dissemination. Vol 226. American Institute of Physics; 1958.
  4. Chen J, Kwong DL, Cao T, Hu Q, Zhang L, Ming X, Chen J, Fu L, Guan X. Esophageal squamous cell carcinoma (ESCC): advance in genomics and molecular genetics. Dis Esophagus. 2015 1;28(1): 84-9. [DOI:10.1111/dote.12088] [PMID]
  5. Esophageal Cancer - Cancer Stat Facts. Accessed July 13, 2022.
  6. Sakaguchi M, Maebayashi T, Aizawa T, Ishibashi N, Saito T. Clinical results of multimodality therapy for esophageal cancer with distant metastasis. J Thoracic Dis. 2018;10(3):1500-10. [DOI:10.21037/jtd.2018.03.45] [PMID] [PMCID]
  7. Li B, Xu WW, King A, et al. Significance of PI3K/AKT Signaling Pathway in Metastasis of Esophageal Squamous Cell Carcinoma and Its Potential as a Target for Anti-Metastasis Therapy.; 2017. [DOI:10.18632/oncotarget.16333] [PMID] [PMCID]
  8. Valastyan S, Weinberg RA. Tumor metastasis: Molecular insights and evolving paradigms. Cell. 2011;147(2):275-92. [PMID] [PMCID] [DOI:10.1016/j.cell.2011.09.024]
  9. Lin KT, Yeh YM, Chuang CM, et al. Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B. Nature Communications. 2015;6. doi:10.1038/ncomms6917 [DOI:10.1038/ncomms6917] [PMID] [PMCID]
  10. Shigaki H, Baba Y, Watanabe M, et al. PIK3CA mutation is associated with a favorable prognosis among patients with curatively resected esophageal squamous cell carcinoma. Clin Can Res. 2013; 19(9):2451-2459. [DOI:10.1158/1078-0432.CCR-12-3559] [PMID]
  11. Yokota T, Serizawa M, Hosokawa A, et al. PIK3CA mutation is a favorable prognostic factor in esophageal cancer: molecular profile by next-generation sequencing using surgically resected formalin-fixed, paraffin-embedded tissue. [DOI:10.1186/s12885-018-4733-7] [PMID] [PMCID]
  12. Andl CD, Mizushima T, Nakagawa H, et al. Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo. J Biol Chem. 2003;278(3):1824-30. [DOI:10.1074/jbc.M209148200] [PMID]
  13. Weaver LT, Walker WA. Epidermal growth factor and the developing human gut. Gastroenterology. 1988;94(3):845-7. [DOI:10.1016/0016-5085(88)90263-6] [PMID]
  14. Wieduwilt MJ, Moasser MM. The epidermal growth factor receptor family: Biology driving targeted therapeutics. doi:10.1007/s00018-008-7440-8 [DOI:10.1007/s00018-008-7440-8] [PMID] [PMCID]
  15. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer. [DOI:10.1038/nrd2926] [PMID] [PMCID]
  16. Yang J, Nie J, Ma X, Wei Y, Peng Y, Wei X. Targeting PI3K in cancer: Mechanisms and advances in clinical trials. Mol Can. 2019;18(1). [DOI:10.1186/s12943-019-0954-x] [PMID] [PMCID]
  17. Cortes-Ciriano I, Lee S, Park WY, Kim TM, Park PJ. A molecular portrait of microsatellite instability across multiple cancers. Nature Communications. 2017;8. [DOI:10.1038/ncomms15180] [PMID] [PMCID]
  18. Jung MK, Shin US, Ki YJ, Kim YB, Moon SM, Sung SJ. Is the location of the tumor another prognostic factor for patients with colon cancer? Annals of Coloproctology. 2017;33(6):210-218. [DOI:10.3393/ac.2017.33.6.210] [PMID] [PMCID]
  19. Sorokin M, Rabushko E, Efimov V, et al. Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability. Front Mol Biosci. 2021;8. [PMID] [PMCID] [DOI:10.3389/fmolb.2021.737821]
  20. Gupta B, Kumar N. Worldwide incidence, mortality and time trends for cancer of the oesophagus. Eur J Cancer Prev. 2017;26(2):107-118. [PMID] [DOI:10.1097/CEJ.0000000000000249]
  21. Abnet CC, Arnold M, Wei WQ. Epidemiology of Esophageal Squamous Cell Carcinoma HHS Public Access. [DOI:10.1053/j.gastro.2017.08.023] [PMID] [PMCID]
  22. Kanehisa Laboratories. KEGG. Accessed December 27, 2021.
  23. Egebjerg K, Garbyal RS, Hasselby JP, Baeksgaard L, Mau-Sørensen M. Prevalence of HER2 overexpression and amplification in squamous cell carcinoma of the esophagus: A systematic review and meta-analysis. Critical Reviews in Oncology/Hematology. 2021;161. [DOI:10.1016/j.critrevonc.2021.103339] [PMID]
  24. Campanella NC, Lacerda CF, Berardinelli GN, et al. Presence of microsatellite instability in esophageal squamous cell carcinoma associated with chagasic megaesophagus. Biomark Med. 2018;12(6):573-582. [DOI:10.2217/bmm-2017-0329] [PMID]
  25. Zhu M, Jin Z, Hubbard JM. cancers Management of Non-Colorectal Digestive Cancers with Microsatellite Instability. Published online 2021. [DOI:10.3390/cancers13040651] [PMID] [PMCID]
  26. Svrcek M, Lascols O, Cohen R, et al. Short Title: Standard for Screening and Diagnosis of MSI/MMR Deficient Tumor.; 2019.
  27. Buhard O, Lagrange A, Guilloux A, et al. HSP110 T17 simplifies and improves the microsatellite instability testing in patients with colorectal cancer. J Med Gen. 2016;53(6):377-384. [DOI:10.1136/jmedgenet-2015-103518] [PMID]
  28. Arsenic R, Treue D, Lehmann A, et al. Comparison of targeted next-generation sequencing and Sanger sequencing for the detection of PIK3CA mutations in breast cancer. BMC Clin Pathol. 2015;15(1). [DOI:10.1186/s12907-015-0020-6] [PMID] [PMCID]