International Journal of Cancer Management

Published by: Kowsar

Immunohistochemical Study of HER2/neu Expression in Colorectal Cancer and its Relation to other Clinicopathological Criteria and Prognostic Factors

Nesa Sayadnejad 1 , Alireza Firouzjahi 1 , Shahryar Shafaee 1 , Hannaneh Golshahi 2 , Zahra Sokouti 1 , Hemmat Gholinia 1 and Mohammad Ranaee 1 , *
Authors Information
1 Department of Pathology, Faculty of Medicine, Babol University of Medical Sciences, Babol, IR Iran
2 Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, IR Iran
Article information
  • International Journal of Cancer Management: May 2017, 10 (5); e5700
  • Published Online: May 6, 2017
  • Article Type: Research Article
  • Received: February 14, 2016
  • Revised: July 19, 2016
  • Accepted: April 29, 2017
  • DOI: 10.5812/ijcm.5700

To Cite: Sayadnejad N, Firouzjahi A, Shafaee S, Golshahi H, Sokouti Z, et al. Immunohistochemical Study of HER2/neu Expression in Colorectal Cancer and its Relation to other Clinicopathological Criteria and Prognostic Factors, Int J Cancer Manag. 2017 ; 10(5):e5700. doi: 10.5812/ijcm.5700.

Copyright © 2017, International Journal of Cancer Management. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Methods
3. Results
4. Discussion
  • 1. Ghanbari R, Mosakhani N, Asadi J, Nouraee N, Mowla SJ, Yazdani Y, et al. Downregulation of Plasma MiR-142-3p and MiR-26a-5p in Patients With Colorectal Carcinoma. Iran J Cancer Prev. 2015; 8(3)[DOI][PubMed]
  • 2. Khorrami S, Zavaran Hosseini A, Mowla SJ, Malekzadeh R. Verification of ALDH Activity as a Biomarker in Colon Cancer Stem Cells-Derived HT-29 Cell Line. Iran J Cancer Prev. 2015; 8(5)[DOI][PubMed]
  • 3. Zeinalian M, Emami MH, Naimi A, Salehi R, Hashemzadeh-Chaleshtori M. Immunohistochemical analysis of mismatch repair proteins in Iranian colorectal cancer patients at risk for lynch syndrome. Iran J Cancer Prev. 2015; 8(1): 11-7[PubMed]
  • 4. Wolin KY, Lee IM, Colditz GA, Glynn RJ, Fuchs C, Giovannucci E. Leisure-time physical activity patterns and risk of colon cancer in women. Int J Cancer. 2007; 121(12): 2776-81[DOI][PubMed]
  • 5. Charles RS. Screening and early diagnosis. Suppl Cancer. 1992; 70: 1246-60
  • 6. Li S, Buchbinder E, Wu L, Bjorge JD, Fujita DJ, Zhu S. EGFR and HER2 levels are frequently elevated in colon cancer cells. Discov Rep. 2014; 1
  • 7. Schlessinger J. Cell Signaling by Receptor Tyrosine Kinases. Cell. 2000; 103(2): 211-25[DOI]
  • 8. Kafi SG, Lari S, Nassiri G. HER2/neu expression in colon adenocarcinoma and its correlation with clinicopathologic variables. IJBMS. 2006; 9(1): 64
  • 9. Dittmar T, Husemann A, Schewe Y, Nofer JR, Niggemann B, Zanker KS, et al. Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c-erbB-2 receptor via EGFR. FASEB J. 2002; 16(13): 1823-5[DOI][PubMed]
  • 10. Kaptain S, Tan LK, Chen B. Her-2/neu and breast cancer. Diagn Mol Pathol. 2001; 10(3): 139-52[PubMed]
  • 11. Schuell B, Gruenberger T, Scheithauer W, Zielinski C, Wrba F. HER 2/neu protein expression in colorectal cancer. BMC Cancer. 2006; 6: 123[DOI][PubMed]
  • 12. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344(11): 783-92[DOI][PubMed]
  • 13. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002; 20(3): 719-26[DOI][PubMed]
  • 14. Le XF, Pruefer F, Bast RJ. HER2-targeting antibodies modulate the cyclin-dependent kinase inhibitor p27Kip1 via multiple signaling pathways. Cell Cycle. 2005; 4(1): 87-95[DOI][PubMed]
  • 15. Ross JS, McKenna BJ. The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest. 2001; 19(5): 554-68[PubMed]
  • 16. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376(9742): 687-97[DOI][PubMed]
  • 17. McKay JA, Loane JF, Ross VG, Ameyaw MM, Murray GI, Cassidy J, et al. c-erbB-2 is not a major factor in the development of colorectal cancer. Br J Cancer. 2002; 86(4): 568-73[DOI][PubMed]
  • 18. Elwy D, El-Aziz AA, El-Sheikh S, Ebrahim H. Immunohistochemical expression of HER2/NEU in colorectal carcinoma. Med J Cairo Univ. 2012; 80(2)
  • 19. Chen J, Li Q, Wang C, Wu J, Zhao G. Prognostic significance of c-erbB-2 and vascular endothelial growth factor in colorectal liver metastases. Ann Surg Oncol. 2010; 17(6): 1555-63[DOI][PubMed]
  • 20. Lu Y, Jingyan G, Baorong S, Peng J, Xu Y, Cai S. Expression of EGFR, Her2 predict lymph node metastasis (LNM)-associated metastasis in colorectal cancer. Cancer Biomark. 2012; 11(5): 219-26[DOI][PubMed]
  • 21. Park DI, Kang MS, Oh SJ, Kim HJ, Cho YK, Sohn CI, et al. HER-2/neu overexpression is an independent prognostic factor in colorectal cancer. Int J Colorectal Dis. 2007; 22(5): 491-7[DOI][PubMed]
  • 22. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007; 25(1): 118-45[DOI][PubMed]
  • 23. Kavanagh DO, Chambers G, O'Grady L, Barry KM, Waldron RP, Bennani F, et al. Is overexpression of HER-2 a predictor of prognosis in colorectal cancer? BMC Cancer. 2009; 9: 1[DOI][PubMed]
  • 24. Jesus EC, Matos D, Artigiani R, Waitzberg AF, Goldenberg A, Saad SS. Assessment of staging, prognosis and mortality of colorectal cancer by tumor markers: receptor erbB-2 and cadherins. Acta Cir Bras. 2005; 20(6): 422-7[PubMed]
  • 25. Blok EJ, Kuppen PJ, van Leeuwen JE, Sier CF. Cytoplasmic Overexpression of HER2: a Key Factor in Colorectal Cancer. Clin Med Insights Oncol. 2013; 7: 41-51[DOI][PubMed]
  • 26. Berg M, Soreide K. Genetic and epigenetic traits as biomarkers in colorectal cancer. Int J Mol Sci. 2011; 12(12): 9426-39[DOI][PubMed]
  • 27. Penault-Llorca F, Bilous M, Dowsett M, Hanna W, Osamura RY, Ruschoff J, et al. Emerging technologies for assessing HER2 amplification. Am J Clin Pathol. 2009; 132(4): 539-48[DOI][PubMed]
  • 28. Wu QB, Sun GP. Expression of COX-2 and HER-2 in colorectal cancer and their correlation. World J Gastroenterol. 2015; 21(20): 6206-14[DOI][PubMed]
  • 29. Seo AN, Kwak Y, Kim DW, Kang SB, Choe G, Kim WH, et al. HER2 status in colorectal cancer: its clinical significance and the relationship between HER2 gene amplification and expression. PLoS One. 2014; 9(5)[DOI][PubMed]
  • 30. Ramieri MT, Murari R, Botti C, Pica E, Zotti G, Alo PL. Detection of HER2 amplification using the SISH technique in breast, colon, prostate, lung and ovarian carcinoma. Anticancer Res. 2010; 30(4): 1287-92[PubMed]
  • 31. Gill MK, Manjari M, Jain K, Manjari M, Kauret T. Expression of Her-2/neu in colon carci¬noma and its correlation with the histological grades and the lymph nodes status. J Clin Diagn Res. 2011; 5: 15648
  • 32. Messerini L, Cianchi F, Cortesini C, Comin CE. Incidence and prognostic significance of occult tumor cells in lymph nodes from patients with stage IIA colorectal carcinoma. Hum Pathol. 2006; 37(10): 1259-67[DOI][PubMed]
  • 33. Cressey R, Pimpa S, Tontrong W, Watananupong O, Leartprasertsuke N. Expression of cyclooxygenase-2 in colorectal adenocarcinoma is associated with p53 accumulation and hdm2 overexpression. Cancer Lett. 2006; 233(2): 232-9[DOI][PubMed]
  • 34. Terzi C, Canda AE, Sagol O, Atila K, Sonmez D, Fuzun M, et al. Survivin, p53, and Ki-67 as predictors of histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiotherapy. Int J Colorectal Dis. 2008; 23(1): 37-45[DOI][PubMed]
  • 35. Neklason DW, Kerber RA, Nilson DB, Anton-Culver H, Schwartz AG, Griffin CA, et al. Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis. Cancer Res. 2008; 68(21): 8993-7[DOI][PubMed]
  • 36. Cancer statistics registrati onr. Registrations of cancer diagnosed in 2008. 2011;
  • 37. Tavangar SM, Shariftabrizi A, Soroush AR. Her–2/neu over-expression correlates with more advanced disease in Iranian colorectal cancer patients. Med Sci Monitor. 2005; 11(3)-6
  • 38. Smyrk TC. Gastrointes-tinal oncology principles and practice. 2002;
  • 39. Sharifi N, Ghaffarzadegan K, Ayatollahi H, Shakeri MT, Sadeghian MH, Azari JB. Evaluation of angiogenesis in colorectal carcinoma by CD34 immunohistochemistry method and its correlation with clinicopathologic parameters. Acta Medica Iranica. 2009; 47(3): 161-4
  • 40. van Triest B, Pinedo HM, Blaauwgeers JL, van Diest PJ, Schoenmakers PS, Voorn DA, et al. Prognostic role of thymidylate synthase, thymidine phosphorylase/platelet-derived endothelial cell growth factor, and proliferation markers in colorectal cancer. Clin Cancer Res. 2000; 6(3): 1063-72[PubMed]
  • 41. Sis B, Sagol O, Kupelioglu A, Sokmen S, Terzi C, Fuzun M, et al. Prognostic significance of matrix metalloproteinase-2, cathepsin D, and tenascin-C expression in colorectal carcinoma. Pathol Res Pract. 2004; 200(5): 379-87[DOI][PubMed]
  • 42. Kruszewski WJ, Rzepko R, Ciesielski M, Szefel J, Zielinski J, Szajewski M, et al. Expression of HER2 in colorectal cancer does not correlate with prognosis. Dis Markers. 2010; 29(5): 207-12[DOI][PubMed]
  • 43. Kim JY, Lim SJ, Park K. Cyclooxygenase-2 and c-erbB-2 expression in colorectal carcinoma assessed using tissue microarrays. Appl Immunohistochem Mol Morphol. 2004; 12(1): 67-70[PubMed]
  • 44. Cunningham MP, Essapen S, Thomas H, Green M, Lovell DP, Topham C, et al. Coexpression, prognostic significance and predictive value of EGFR, EGFRvIII and phosphorylated EGFR in colorectal cancer. Int J Oncol. 2005; 27(2): 317-25[PubMed]
  • 45. Pappas A, Lagoudianakis E, Seretis C, Tsiambas E, Koronakis N, Toutouzas K, et al. Clinical role of HER-2/neu expression in colorectal cancer. J BUON. 2013; 18(1): 98-104[PubMed]
  • 46. Half EE, Bresalier RS. Clinical management of hereditary colorectal cancer syndromes. Curr Opin Gastroenterol. 2004; 20(1): 32-42[PubMed]
  • 47. Kountourakis P, Pavlakis K, Psyrri A, Rontogianni D, Xiros N, Patsouris E, et al. Clinicopathologic significance of EGFR and Her-2/neu in colorectal adenocarcinomas. Cancer J. 2006; 12(3): 229-36[PubMed]
  • 48. Koretz K, Schlag P, Moller P. Expression of epidermal growth factor receptor in normal colorectal mucosa, adenoma, and carcinoma. Virchows Arch A Pathol Anat Histopathol. 1990; 416(4): 343-9[PubMed]
  • 49. Deng W, Dong WG, Zhan N, Zhan F, Wu HX. Human epidermal growth factor receptor (HER 2)/neu expression and gene amplification in colorectal cancer. Afr J Biotechnol. 2011; 10(74): 16732-9
  • 50. Demirbas S, Sucullu I, Yildirim S, Celenk T. Influence of the c-erb B-2, nm23, bcl-2 and p53 protein markers on colorectal cancer. Turk J Gastroenterol. 2006; 17(1): 13-9[PubMed]
  • 51. Asonuma K, Date Y, Tsukuda G, Hirabayashi K, Wada Y, Takahashi H, et al. Expression of HER2 and MUC1 in Advanced Colorectal Cancer: Frequency and Clinicopathological Characteristics. Showa Univ J Med Sci. 2013; 25(2): 93-100[DOI]
  • 52. Nathanson DR, Culliford A, Shia J, Chen B, D'Alessio M, Zeng ZS, et al. HER 2/neu expression and gene amplification in colon cancer. Int J Cancer. 2003; 105(6): 796-802[DOI][PubMed]
  • 53. Sorscher SM. Marked response to single agent trastuzumab in a patient with metastatic HER-2 gene amplified rectal cancer. Cancer Invest. 2011; 29(7): 456-9[DOI][PubMed]
  • 54. Ramanathan RK, Hwang JJ, Zamboni WC, Sinicrope FA, Safran H, Wong MK, et al. Low overexpression of HER-2/neu in advanced colorectal cancer limits the usefulness of trastuzumab (Herceptin) and irinotecan as therapy. A phase II trial. Cancer Invest. 2004; 22(6): 858-65[PubMed]
Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments