Expressional Correlation of Human Epidermal Growth Factor Receptor 2, Estrogen/Progesterone Receptor and Protein 53 in Breast Cancer

  • Panahi, Marzieh (Department of Histology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences) ;
  • Saki, Najmaldin (Thalassemia and Hemoglobinopathies Research Center, Ahvaz Jundishapur University of Medical Sciences) ;
  • Ashourzadeh, Sara (Thalassemia and Hemoglobinopathies Research Center, Ahvaz Jundishapur University of Medical Sciences) ;
  • Rahim, Fakher (Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences)
  • Published : 2013.06.30


Background: This study aimed to show the localization of estrogen / progesterone receptors, human epidermal growth factor receptor 2 (Her-2) and protein 53 (p53) by immunohistochemistry in a series of consecutive breast cancer patients. Materials and Methods: The study covered invasive breast cancers from 299 patients presenting at the Oncogenetic Clinic and Pathology Centers of Ahwaz Jondishapour University of Medical Sciences Hospital in Iran during the time period from 2009 to 2011. The Scarff-Bloom Richardson scoring method was used. Results: Of the 299, 27% (80/299) were <40, 33% (100/299) were 41-50, and the remaining 40% (119/299) were>50 years old. The highest incidence of breast cancer in this study population was in the group of more than 50 year age, and the most common histological type of breast cancer was the invasive ductal carcinoma, which accounted for 68% (203/299) of the cases. Out of possible total of 207, 6% (13/207), 41% (85/207), and 53% (109/207) were scored as grade I, II, III, respectively. Conclusion: Our findings demonstrated a lack of association between labeling for the markers studied and tumor size and age of the patients. We confirmed an association between ER labeling and nuclear grade of breast cancer. The conflicting results obtained compared with the literature be because of differences in the immunohistochemical techniques applied in the various studies and to the scoring systems used.


Breast cancer;estrogen receptor (ER);progesterone receptor (PR);p53


  1. Barnes DM, Lammie GA, Millis RR, et al (1988). An immunohistochemical evaluation of c-erbB-2 expression in human breast carcinoma. Br J Cancer. 58, 448-52.
  2. Bertucci F, Finetti P, Rougemont J, et al (2005). Gene expression profiling identifies molecular subtypes of inflammatory breast cancer. Cancer Res. 65, 2170-8.
  3. Bull SB, Ozcelik H, Pinnaduwage D, et al (2004). The combination of p53 mutation and neu/erbB-2 amplification is associated with poor survival in node-negative breast cancer. J Clin Oncol. 22, 86-96.
  4. Chang HY, Nuyten DS, Sneddon JB, et al (2005). Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci USA, 102, 3738-43.
  5. Chang HY, Sneddon JB, Alizadeh AA, et al (2004). Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol, 2, 206-14.
  6. Cho EY, Choi YL, Han JJ, Kim KM, Oh YL (2008). Expression and amplification of Her2, EGFR and cyclin D1 in breast cancer: immunohistochemistry and chromogenic in situ hybridization. Pathol Int, 58, 17-25.
  7. Dairkee SH, Luciani-Torres MG, Moore DH, Goodson WH (2013). Bisphenol-A-induced inactivation of the p53 axis underlying deregulation of proliferation kinetics, and cell death in non-malignant human breast epithelial cells. Carcinogenesis, 34, 703-12.
  8. Deblois G, Giguere V (2013). Oestrogen-related receptors in breast cancer: control of cellular metabolism and beyond. Nat Rev Cancer, 13, 27-36.
  9. Ellis MJ, Tao Y, Young O, et al (2006). Estrogen-independent proliferation is present in estrogen-receptor HER2-positive primary breast cancer after neoadjuvant letrozole. J Clin Oncol. 24, 3019-25.
  10. Elston CW, Ellis IO (2002). Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term followup. Histopathology, 41, 154-61.
  11. Erdem O, Dursun A, Coskun U, Gunel N (2005). The prognostic value of p53 and c-erbB-2 expression, proliferative activity and angiogenesis in node-negative breast carcinoma. Tumori, 91, 46-52.
  12. Esteva-Lorenzo FJ, Sastry L, King CR (1998). The erbB-2 gene: from research to application. In: Dickson RB, Salomon DS., editor. In Hormones and Growth Factors in Development and Neoplasia. New York: John Wiley & Sons. 421-44.
  13. Fasching PA, Pharoah PD, Cox A, et al (2012). The role of genetic breast cancer susceptibility variants as prognostic factors. Hum Mol Genet. 21, 3926-39.
  14. Habashy HO, Powe DG, Glaab E, et al (2011). RERG (Ras-like, oestrogen-regulated, growth-inhibitor). expression in breast cancer: a marker of ER-positive luminal-like subtype. Breast Cancer Res Treat, 128, 315-26.
  15. Harirchi I, Karbakhsh M, Montazeri A, et al (2010). Decreasing trend of tumor size and downstaging in breast cancer in Iran: results of a 15-year study. Eur J Cancer Prev, 19, 126-30.
  16. Jehoram TA, Bency J, Sitara A, et al (2005). Relationship between the expression of various markers and prognostic factors in breast cancer. Acta Histochimica, 107, 87-93.
  17. Kazkayasi M, Hucumenoglu S, Siriner GI, Hucumenoglu M (2001). Over-expression of p53 and c-erbB-2 oncoproteins in laryngeal carcinoma. Eur Arch Otorhinolaryngol, 258, 329-35.
  18. Khosravi A, Taylor R, Naghavi M, Lopez AD (2007). Differential mortality in Iran. Popul Hlth Metr, 28, 5-7.
  19. Lagiou P, Georgila C, Samoli E, et al (2009). Estrogen alpha and progesterone receptor expression in the normal mammary epithelium in relation to breast cancer risk. Int J Cancer, 124, 440-2.
  20. Lee S, Mohsin SK, Mao S, et al (2006). Hormones, receptors, and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer. Breast Cancer Res, 8, 1-9.
  21. Ma XJ, Wang Z, Ryan P, et al (2004). A two gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell, 5, 607-16.
  22. Matsuda T, Matsuda A (2013). Burden of cancer incidence below the age of 40 in Asia 2002 extrapolated from the Cancer Incidence in Five Continents Vol. IX. Jpn J Clin Oncol, 43, 449-50.
  23. Mohagheghi MA, Mosavi-Jarrahi A (2010). Review of cancer registration and cancer data in Iran, a historical prospect. Asian Pac J Cancer Prev, 11, 1155-7.
  24. Mousavi SM, Montazeri A, Mohagheghi MA, et al (2007). Breast cancer in Iran: an epidemiological review. Breast J, 13, 383-91.
  25. Muller V, Thomssen C, Karakas C, et al (2003). Quantitative assessment of HER-2/neu protein concentration in breast cancer by enzyme-linked immunosorbent assay. Int J Biol Markers, 18, 13-20.
  26. Ouyang X, Gulliford T, Zhang H, et al (2001). Association of ErbB2 Ser1113 phosphorylation with epidermal growth factor receptor co-expression and poor prognosis in human breast cancer. Mol Cell Biochem, 218, 47-54.
  27. Paik S, Shak S, Tang G, et al (2004). A multigene assay to predict recurrence of tamoxifen- treated node-negative breast cancer. N Engl J Med, 351, 2817-26.
  28. Patsialou A, Wang Y, Lin J, et al (2012). Selective geneexpression profiling of migratory tumor cells in vivo predicts clinical outcome in breast cancer patients. Breast Cancer Res, 14, 139.
  29. Rody A, Holtrich U, Pusztai L, et al (2009). T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers. Breast Cancer Res, 11, 15.
  30. Rosenthal SI, Depowski PL, Sheehan CE, Ross JS (2002). Comparison of HER-2/neu oncogene amplification detected by fluorescence in situ hybridization in lobular and ductal breast cancer. Appl Immunohistochem Mol Morphol, 10, 40-6.
  31. Rudas M, Neumayer R, Gnant MFX, et al (1997). p53 protein expression, cell proliferation and steroid hormone receptors in ductal and lobular in situ carcinomas of the breast. Eur J Cancer, 33, 39-44.
  32. Schonborn I, Zschieseche W, Spitzer E, et al (1994). C-erb-2 overexpression in primary breast cancer: independent prognostic factor in patients at high risk. Breast Cancer Res Treat, 29, 287-95.
  33. Skalova A, Sima R, Vanecek T, et al (2009). Acinic cell carcinoma with high-grade transformation: a report of 9 cases with immunohistochemical study and analysis of TP53 and HER-2/neu genes. Am J Surg Pathol, 33, 1137-45.
  34. Sorlie T, Tibshirani R, Parker J, et al (2003). Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A .100, 8418-23.
  35. Sotiriou C, Neo SY, McShane LM, et al (2003). Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA, 100, 10393-8.
  36. Szoke J, Udvarhelyi N (2012). Modern pathologic diagnostics in breast cancer. Orv Hetil. 153, 22-30.
  37. Thor AD, Berry DA, Budman DR, et al (1998). erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst, 90, 1346-60.
  38. Tian Y, Chen B, Guan P, Kang Y, Lu Z (2013). A Prognosis Classifier for Breast Cancer Based on Conserved Gene Regulation between Mammary Gland Development and Tumorigenesis: A Multiscale Statistical Model. PLoS One, 8, 60131.
  39. Tsuda H (2009). Gene and chromosomal alterations in sporadic breast cancer: correlation with histopathological features and implications for genesis and progression. Breast Cancer, 16, 186-201.
  40. Umekita Y, Ohi Y, Sagara Y, Yoshida H (2000). Co-expression of epidermal growth factor receptor and transforming growth factor-alpha predicts worse prognosis in breast-cancer patients. Int J Cancer, 89, 484-7.<484::AID-IJC3>3.0.CO;2-S
  41. van de Vijver MJ, He YD, van ‘t Veer LJ, et al (2002). A geneexpression signature as a predictor of survival in breast cancer. N Engl J Med, 347, 1999-2009.
  42. Wang Y, Klijn JG, Zhang Y et al (2005). Gene expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet, 365, 671-9.
  43. Yang SX, Loo WT, Chow LW, et al (2012). Decreased expression of C-erbB-2 and CXCR4 in breast cancer after primary chemotherapy. J Transl Med, 10, 1-3.
  44. Yenidunya S, Bayrak R, Haltas H (2011). Predictive value of pathological and immunohistochemical parameters for axillary lymph node metastasis in breast carcinoma. Diagn Pathol. 13, 6-18.

Cited by

  1. in Breast Cancer vol.2014, pp.1875-8630, 2014,
  2. Overexpression of Cyclin E and its Low Molecular Weight Isoforms Cooperate with Loss of p53 in Promoting Oncogenic Properties of MCF-7 Breast Cancer Cells vol.16, pp.17, 2015,