Association of Human Epidermal Growth Factor Receptor-2 Expression and Clinicopathological Findings in Patients with Colorectal Cancer

  • Karaca, Halit (Deparment of Medical Oncology, Erciyes University Medical Faculty) ;
  • Deniz, Kemal (Deparment of Pathology, Erciyes University Medical Faculty) ;
  • Berk, Veli (Deparment of Medical Oncology, Erciyes University Medical Faculty) ;
  • Inanc, Mevlude (Deparment of Medical Oncology, Erciyes University Medical Faculty) ;
  • Ozkan, Metin (Deparment of Medical Oncology, Erciyes University Medical Faculty)
  • Published : 2012.12.31


Background: To determine the frequency of HER-2 overexpression in colorectal cancer (CRC) patients, and to explore the relationship between clinicopathological prognostic factors and their effects on survival, based on immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis. Materials and Methods: The study included 80 patients with a histologically proven diagnosis of CRC that received adjuvant FOLFOX-4 chemotherapy at our department between March 2006 and September 2010. Patient data were analyzed retrospectively. Results: The median follow-up period and age of the patients were 24 months and 59 years, respectively. In immunohistochemical staining, 3+ staining was found in 2 patients (2.5%) while 2+ was in 13 (16%). FISH for HER-2 was performed for all of these 15 patients; samples which were 3+ showed positivity but the ones with 2+ were negative. There was no significant correlation between HER-2 expression and age, gender, tumor localization, histological subtype, grade, lymphovascular and perineural invasion, or pTN stage (P>0.05), even when the patients with HER-2 overexpression were analyzed separately. There was also no significant relationship between progression-free survival (PFS) and overall survival (OS), and HER-2 expression, gender, tumor localization, obstruction-perforation, bleeding, histological type, grade, lymphovascular and perineural invasion, or pT staging (P>0.05); however, there was a significant relationship between lymph node involvement, and PFS and OS (P<0.05). Conclusions: Evaluation of HER-2 overexpression in a more comprehensive, multi-center, prospective trial with standardized methods will be an appropriate approach.


Adjuvant therapy;colorectal cancer;epidermal growth factor receptor;HER-2


  1. Tsioulias GJ, Muto T, Morioka Y, et al (1990 ). erbB-2 gene expression in colorectal cancer. Jpn J Exp Med, 60, 343-9.
  2. Wang SC, Hung MC (2001). HER2 overexpression and cancer targeting. Semin Oncol, 16, 115-24.
  3. Wolmark N, Fisher B, Wieand HS. Et al (1986). The prognostic value of the modifications of the Dukes'C class of colorectal cancer. Ann Surg, 203, 115.
  4. Kountourakis P, Pavlakis K, Psyrri A, et al (2006). Clinicopathologic significance of EGFR and Her-2/neu in colorectal adenocarcinomas. Cancer J, 12, 229-36.
  5. Kruszewski WJ, Rzepko R, Ciesielski M, et al (2010). Expression of HER2 in colorectal cancer does not correlate with prognosis. Disease Markers, 29, 207-12.
  6. Landgraf R (2007). HER2 (ERBB2): functional diversity from structurally conserved building blocks. Breast Cancer Res, 9, 202.
  7. Libutti SK, Saltz LB, Tepper JE, et al (2008). Colon cancer. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. Devita, Hellman and Rosenberg's Cancer: Principles & Practice of Oncology. Philadelphia, PA: Lippincott Williams & Wilkins, 1232-85.
  8. Mann M, Sheng H, Shao J, et al (2001). Targeting cyclooxygenase 2 and HER-2/neu pathway inhibits colorectal carcinoma growth. Gastroenterology, 120, 1713-9.
  9. McCann A, Dervan PA, Johnston PA, et al (1990). C-erbB-2 oncoprotein expression in primary human tumors. Cancer, 65, 88-92.<88::AID-CNCR2820650119>3.0.CO;2-Z
  10. Mendelsohn J, Baselgab J (2006). Epidermal growth factor receptor targeting in cancer. Semin Oncol, 33, 369-85.
  11. Molaei M, Pejhan, S Nayer BN, et al (2009). Human epidermal growth factor receptor-2 family in colorectal adenocarcinoma: correlation with survival and clinicopathological findings. Eur J Gastroenterol Hepatol, 21, 289-93.
  12. Nathanson DR, Culliford AT, Shia J, et al (2003). HER 2/neu expression and gene amplification in colon cancer. Int J Cancer, 105, 796-802.
  13. Ochs AM, Wong L, Kakani V, et al (2004). Expression of Vascular Endothelial Growth Factor and HER2/neu in Stage II Colon Cancer and Correlation with Survival. Clinical Colorectal Cancer, 4, 262-7.
  14. Ooi A, Takehana T, Li X, et al (2004). Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers: an immunohistochemical and fluorescent in situ hybridizationstudy. Mod Pathol, 17, 895-904.
  15. Osako T, Miyahara M, Uchino S, et al (1998). Immunohistochemical study of c-erbB2 protein in colorectal cancer and correlation with patient survival. Oncology, 55, 548-55.
  16. Park D, Kang MS, Oh SJ, et al (2007). HER-2/neu overexpression is an independent prognostic factor in colorectal cancer. Int J Colorectal Dis, 22, 491-7.
  17. Ramanathan RK, Hwang JJ, Zamboni WC, et al (2004). 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, 22, 858-65.
  18. Rossi HA, Liu Q, Banner B et al (2002). The prognostic value of invariant chain (Ii) and HER-2/neu expression in curatively resected colorectal cancer. Cancer J, 8, 268-75.
  19. Sorscher SM (2011). Marked response to single agent trastuzumab in a patient with metastatic HER-2 gene amplified rectal cancer. Cancer Invest, 29, 456-9.
  20. Al-Kuraya K, Novotny H, Bavi P, et al (2007). HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer. J Clin Pathol, 60, 768-72.
  21. Bang YJ, Van Cutsem E, Feyereislova A, et al (2010). 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, 376, 687-97.
  22. Bardelli A, Siena S (2010). Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol, 28, 1254-61.
  23. Baselga J, Swain SM (2009). Novel anticancer target: revisiting ERBB2 and discovering ERBB3. Nature Rev Cancer, 9, 463-75.
  24. Blumberg D, Ramanathan RK (2002). Treatment of colon and rectal cancer. J Clin Gastroenterol, 34, 15-26.
  25. Cunningham D, Humblet Y, Siena S, et al (2004). Cetuximab monotherapy and cetuximab plus irinotecan in irinotecanrefractory metastatic colorectal cancer. N Engl J Med, 351, 337-45.
  26. Cunningham D, Atkin W, Lenz H-J, et al (2010 ). Colorectal cancer. Lancet, 375, 1030-47.
  27. Di NF, Martini M, Molinari F, et al (2008). Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol, 26, 5705-12.
  28. Eugene R, Charles L (2011). Dual HER-2 targeted approaches in HER-2 positive breast cancer. Breast Cancer Res Treat, 10, 1781.
  29. Ferretti G, Felici A, Papaldo P, et al (2007). HER2/neu role in breast cancer: from a prognostic foe to a predictive friend. Curr Opin Obstet Gynecol, 19, 56-62.
  30. Giantonio BJ, Catalano PJ, Meropol NJ, et al (2007). Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group study E3200. J Clin Oncol, 25, 1539-44.
  31. Half E, Broaddus R, Danenberg KD, et al (2004). HER-2 receptor expression, localization, and activation in colorectal cancer cell lines and human tumors. Int J Cancer, 108, 540-8.
  32. Jemal A, Siegel R, Xu J, et al (2010). Cancer Statistics, 2010. CA Cancer J Clin, 60, 277-300.
  33. Kapitanovic S, Radosevic S, Kapitanrovic M, et al (1997). The expression of p185HER-2/neu correlates with the stage of disease and survival in colorectal cancer. Gastroenterology, 112, 1103-13.
  34. Karaca H, Berk V, Inanc M, et al (2011). Epidemiologic evaluation of the patients admitted to department of medical oncology, Erciyes University, Medical Faculty, between 2006 and 2009. J Hlth Sci, 20, 1-8.
  35. 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.
  36. Kay EW, Mulcahy H, Walsh CB, et al (1994). Cytoplasmatic c-erbB-w protein expression correlates with survival in Dukes' B colorectal carcinoma. Histopathology, 25, 455-61.
  37. Albarello L, Pecciarini L, Doglioni C, et al (2011). HER2 testing in gastric cancer. Adv Anat Pathol, 18, 53-9.

Cited by

  1. Platelet Derived Growth Factor-B and Human Epidermal Growth Factor Receptor-2 Polymorphisms in Gall Bladder Cancer vol.16, pp.14, 2015,
  2. Types of Cancers Prevailing in Pakistan and their Management Evaluation vol.16, pp.9, 2015,