Survey of HER2-neu Expression in Colonic Adenocarcinoma in the West of Iran

  • Madani, Seyed-Hamid (Molecular Pathology Research Center, Imam Reza Hospital) ;
  • Sadeghi, Edris (Cancer Research Center, Kermanshah University of Medical Sciences) ;
  • Rezaee, Akram (Molecular Pathology Research Center, Imam Reza Hospital) ;
  • Sadeghi, Masoud (Medical Biology Research Center, Kermanshah University of Medical Sciences) ;
  • Khazaee, Sedigheh (Molecular Pathology Research Center, Imam Reza Hospital) ;
  • Amirifard, Nasrin (Cancer Research Center, Kermanshah University of Medical Sciences) ;
  • Payandeh, Mehrdad (Medical Biology Research Center, Kermanshah University of Medical Sciences)
  • Published : 2015.12.03


Background: Overexpression of HER2-neu has been reported in many epithelial malignancies, including cancers of the breast, ovaries, lungs, prostate, bladder, pancreas, colorectum and stomach as well as osteosarcomas. The aim of this study was evaluation of expression of HER2-neu immunohistochemistry (IHC) status and clinicopathologic features in a series of colonic adenocarcinomas. Materials and Methods: In this descriptive and analytical study, we surveyed 211 samples of colon adenocarcinoma from 182 patients (86.3%) undergoing total or partial colectomy and 29 (7.13%) with biopsies by colonoscopy. A sufficient sample size was obtained from all cases and the slides were stained with hematoxylin and eosin and also by IHC (HER2) staining. Results: The mean age for the patients at diagnosis was 57.9 years (range, 15-88 years). One hundred and twenty one patients (57.3%) were male. Of all patients, 201 samples (95.3%) were conventional adenocarcinomas (159, 29 and 13 cases were well, moderately and poorly differentiated, respectively) and 10 (4.7%) were mucinous type. Out of 211 cases, 171 were checked for lymph nodes metastasis and 64 were positive. There is a correlation between HER2 scores and differentiation, most score 3 cases being well differentiated (P<0.05). Conclusions: In patients with advanced colon cancer, surgery alone is not curative and other forms of therapy may be required to prolong patient survival. HER2 overexpression was found in some cases and this could be a guideline to new adjuvant therapy for these patients.


Colon cancer;Her2-neu;IHC;differentiation;Iran


  1. Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T (1986). The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science, 232, 1644-6.
  2. Andersen TI, Paus E, Nesland JM, McKenzie SJ, Borresen AL (1995). Detection of c-erbB-2 related protein in sera from breast cancer patients. Relationship to ERBB2 geneamplification and c-erbB-2 protein overexpression in tumour. Acta Oncol, 34, 499-504.
  3. Blok EJ, Kuppen PJ, van Leeuwen JE, Sier CF (2013). Cytoplasmic Overexpression of HER2: a Key Factor in Colorectal Cancer. Clin Med Insights Oncol, 7, 41-51.
  4. Caruso ML, Valentini AM (1996). Immunohistochemical p53 overexpression correlated to c-erbB-2 and cathepsin D proteins in colorectal cancer. Anticancer Res, 16, 3813-8.
  5. Farzand S, Siddique T, Saba K, Bukhari MH (2014). Frequency of HER2/neu overexpression in adenocarcinoma of the gastrointestinal system. World J Gastroenterol, 20, 5889-96.
  6. Golijow C, Guerci A, Mouron S, et al (2001). Activation of K-ras and c-erbB-2 protooncogenes in human colonic adenocarcinomas. Acta Gastroenterol Latinoam, 31, 71-6.
  7. Half E, Broaddus R, Danenberg KD, et al(2004). HER-2 receptor expression, localization, and activation in colorectal cancercell lines and human tumors. Int J Cancer, 108, 540-8.
  8. Jesus EC, Matos D, Artigiani R, et al (2005). Assessment of staging, prognosis and mortality of colorectal cancer by tumor markers: receptor erbB-2 and cadherins. Acta Cir Bras, 20, 422-27.
  9. Kavanagh DO, Chambers G, O'Grady L, et al (2009). Is overexpression of HER-2 a predictor of prognosis in colorectal cancer? BMC Cancer, 9, 1-6.
  10. Kim MA, Lee HJ, Yang HK, Bang YJ, Kim WH(2011). Heterogeneous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB2status of primary and metastatic lesions in gastric carcinoma. Histopathology, 59, 822-31.
  11. Leung SP, Griffith OL, Masoudi H, et al (2008). Clinical utility of type 1 growth factor receptor expression in colon cancer. Am J Surg, 195, 604-10.
  12. Li Q, Wang D, Li J, Chen P (2011). Clinicopathological and prognostic significance of HER-2/neu and VEGF expression in coloncarcinomas. BMC Cancer, 27, 11, 277.
  13. Maurer CA, Friess H, Kretschmann B, et al (1998). Increased expression of erbB3 in colorectal cancer is associated with concomitant increase in the level of erbB2. Hum Pathol, 29, 771-7.
  14. McKay JA, Loane JF, Ross VG, et al (2002). c-erbB-2 is not a major factor in the development of colorectal cancer. Br J Cancer, 86, 568-73.
  15. Nathason DR, Culliford AT, Shia J, et al (2003). HER-2/neu expression and gene amplification in colon cancer. Int J Cancer, 105, 796-802.
  16. Nazemalhosseini Mojarad E, Kuppen PJ (2013). HER2 and immunotherapy using monoclonal antibodies in colorectal cancer. Immunotherapy, 5, 1267-9.
  17. Payandeh M , Sadeghi M, Sadeghi E, Gholami F (2015). Analysis of KRAS, BRAF and NRAS in Patients with Colorectal Cancer: the First Report of Western Iran. American J Cancer Prev, 3, 9-22.
  18. Porebska I, Harlozinska A, Bojarowski T (2000). Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas. Tumour Biol, 21, 105-15.
  19. Ross JS, McKenna BJ(2001). The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest, 19, 554-68.
  20. Rusch V, Baselga J, Cordon-Carlo, et al (1993). Differential expression of the epidermal growth factor receptor and its ligand in primary non-small cell lung cancers and adjusent benign lung. Cancer Res, 53, 2379-85.
  21. Schuell B, Gruenberger T, Scheithauer W, Zielinski Ch, Wrba F (2006). HER 2/neu protein expression in colorectal cancer. BMC Cancer, 6, 123.
  22. Shan L, Ying J Lu (2013). HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population. Diagn Pathol, 8, 76.
  23. Sun XF, Carstensen JM, Sta l O, Zhang H, Nordenskjold B (1996). Proliferating cell nuclear antigen (PCNA) in relation to ras, c-erbB-2,p53, clinico-pathological variables and prognosis in colorectal adenocarcinoma. Int J Cance, 69, 5-8.<5::AID-IJC2>3.0.CO;2-8
  24. Wolff AC, Hammond MEH, Schwartz JN, et al (2007). American society of clinical oncology/college of American pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Archives of Pathology and Laboratory Medicine, 131, 18-43.