THE ASSOCIATION OF HER-2/NEU OVER-EXPRESSION IN RELATION TO P53 NUCLEAR ACCUMULATION, HORMONAL RECCEPTOR STATUS AND COMMON CLINICO-PATHOLOGICAL PROGNOSTIC PARAMETERS IN A SERIES OF EGYPTIAN WOMEN WITH INVASIVE DUCTAL CARCINOMA

Year 2007, Volume: 4 Issue: 2, 73 - 79, 01.06.2007

Mona M Rashed Noha M Ragab Manal K Galal

Abstract

-

Keywords

-

THE ASSOCIATION OF HER-2/NEU OVER-EXPRESSION IN RELATION TO P53 NUCLEAR ACCUMULATION, HORMONAL RECCEPTOR STATUS AND COMMON CLINICO-PATHOLOGICAL PROGNOSTIC PARAMETERS IN A SERIES OF EGYPTIAN WOMEN WITH INVASIVE DUCTAL CARCINOMA

Abstract

Aim: HER2/neu protein has garnered a great deal of interest in the popular media. However, it has long been known among pathologists and oncologists for its potential role as a tumor and prognostic marker. This protein exists on the surface of epithelial cells and functions in the normal cell as a receptor for a cellular growth factor. Aim of the study: is to determine the association of HER-2/neu and p53 as well as hormonal receptor status with common pathologic parameters in invasive ductal carcinoma of the breast. Methods: Expression of HER-2/neu and p53 was examined by immunohistochemistry in samples of breast tissue from 50 patients with invasive ductal carcinoma and their significance for prognosis was analyzed. Results: There was a significant association between HER-2 over-expression and the accumulation of nuclear p53 (p=0.0017), the increased size of tumor (p=0.0115) as well as the high grade tumors (p=0.0001). On the other hand HER-2 over-expression showed an inverse significant association with ER (p=0.0001) and PR status (p=0.0003). Meanwhile there wasn’t any significant association of HER-2 over-expression with the number of the invaded lymph nodes, grade of tumor necrosis or the menopausal status. Conclusion: The study had indicated that Her-2/neu may be a powerful predictor of poor prognosis as it’s over-expression was strongly directly correlated with p53 nuclear accumulation, tumor size and grade and inversely correlated with hormonal receptor status of breast carcinoma. Meanwhile; no significant associated for number of invaded lymph nodes and the menopausal status

Keywords

Immunohistochemistry, Her-2/neu, p53, hormone receptors, clinico-pathological parameters, breast cancer

References

• Al-Moundhri M, Nirmala V, Al-Mawaly K, et al. Significance of p53, Bcl-2 and Her-2/neu protein expression in Omani Arab females with breast cancer. Pathol Oncol Res 2003;9:226-31
• Yamashita H, Nishio M, Toyama T, et al. Coexistence of HER-2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer. Breast Cancer Res 2004;6:24-30
• Meenakshi A, Kumar RS, Ganesh V, et al. Immunohistochemical assay (IHC) to study C-erbB-2 status of breast cancer using monoclonal antibody CIBCgp185. Hum Antibodies 2003;12(4):123-7
• Diaz NM. Laboratory testing for Her- 2/neu in breast carcinoma: An evolving strategy to predict response to targeted therapy. Cancer Control 2001;8(5):415-8
• Hudziak RM, Lewis GD, Shalaby MR, et al. Amplified expression of the HER- 2/ErbB2 oncogene induces resistance to tumor necrosis factor alpha in NIH3T3 cells. Proc Natl Acad Sci USA 1988; 85(14):5102-6
• Zhou BP, Hu MC, Miller SA, et al. HER-2/neu blocks tumor necrosis factor induced apoptosis via the Akt/NF-kappa B pathway. J Biol Chem 2000;275(11): 8027-31
• Rosenblum MG, Horn SA & Cheung LH. A novel recombinant fusion toxin targeting HER-2/neu over expressing cells and containing human tumor necrosis factor. Int J Cancer 2000;88(2):267-73
• Scarff RW, Torloni H. Histological typing of breast tumors. 1968 International histological classification of tumors. World Health Organization, Geneva,no2 vol2; pp 13-20
• Hlupic L, Jakic-Razumovic J, Bozikov J, et al. Prognostic value of different factors in breast carcinoma. Tumori 2004;90(1): 112-9
• Sorli T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguishes tumor subclasses with clinical implication. PNAS 2001;98(19):10869-74
• Winters ZE, Leek RD, Bradurn MJ, et al. Cytoplasmic p21 WAF1/CIP1 expression is correlated with HER-2/neu in breast cancer and is an independent predictor of prognosis. Breast Cancer Res 2003;5: 242-9
• Salmon DJ, Clark GM, Wong SG, et al. Human breast cancer. Correlation of relapse and survival with amplification of the Her-2/neu oncogene. Science 1987; 235:177-82
• Ross JS, Fletcher JA. The Her-2/neu oncogene in breast cancer: Prognostic factor, prediction factor and target for therapy. Oncologist 1998;3(4):237-52
• Huang WY, Newman B, Millikan RC, et al. Risk of breast cancer according to the status of Her-2/neu oncogene amplification. biomarkers & Prevention 2000;9:65-71
• Nieto Y, Cagnoni PJ, Nawaz S, et al. Evaluation of the predictive value of Her- 2/neu over expression and p53 mutations in high risk primary brest cancer patients treated with high dose chemotherapy and autologous stem cell transplantation. J Clin Oncol 2000;18(10):2070-80
• Guerra I, Algorta J, Díaz de Otazu R. Immunohistochemical prognostic index for breast cancer in young women. Molecular Pathology 2003;56:323-7
• Smith CA, Pollice AA, Gu LP et al. Correlations among p53, Her-2/neu and ras over expression and aneuploidy by multiparameter flow cytometry in human breast cancer: Evidence for a common phenotypic evolutionary pattern in infilterating ductal carcinoma. Clinical Cancer Res 2000;16:112-6
• Marks JR, Humphrey PA, Wu K, et al. Over expression of p53 and HER- 2/neu proteins as prognostic markers in early stage breast cancer. Ann Surg 1994;219(4):332-41
• Tsutsui S, Ohno S, Murakami S, et al. Prognostic significance of the co- expression of p53 protein and c-erbB2 in breast cancer. Am J Surg 2003;185(2): 165-7
• Konecny G, Pauletti G, Pegram M, et al. Quantitive associated between Her-2/neu and steroid hormone receptors-positive primary breast cancer. JNCI 2003;95(2): 142-53
• Thor A. Are patterns of Her-2/neu amplification and expression among primary indicative of distance metastasis and predictive of herceptin response? JNCI 2001;93(15):1112-21 metastasis
• Menard S, Frotis S, Castiglioni F, et al. HER-2 as a prognostic factor in breast cancer. Oncology 2001;61(suppl 2):67- 72
• Swede H, Moysich KB, Winston JS et al. Variation of the prognostic significance of Her-2 expression in breast cancer according to tumor size. Breast J. 2003 Mar-Apr; 9(2):98-105
• Ray A, Sharma BK, Kaur S, et al. Over expression of c-erbB2 oncoprotein and associated pathobiological factors in invasive primary breast cancer. Indian J Exp Biol 2004;42(3):253-8
• Climent MA, Segui MA, Molina R, et al. Prognostic value of HER-2/neu and p53 expression in node positive breast cancer. HER-2/neu effect on adjuvant tamoxifen treatment. Breast 2001;10(1):67-77
• Sutterlin MW, Haller A, Gassel AM, et al. The correlation of c-erbB2 oncoprotein and established prognostic factors in human breast cancer. Anticancer Res 2000;20(6D):5083-8
• Korkolis DP, Tsoli E, Fouskakis D, et al. Tumor histology and stage but not p53, Her-2/neu or cathepsin-D expressions are independent prognostic factors in breast cancer patients. Anticancer Res 2004;24(3b):2061-8
• Nishikawa K, Satoh H, Hirai, A et al. alpha-Tocopheryloxy butyric acid enhances necrotic cell death in breast cancer cell treated with chemotherapy agent. Cancer lett. 2003;201(1):51-6
• Bobrow LG, Happerfield LG, Gregory WM, et al. Ductal carcinoma in situ: assessment of necrosis and nuclear morphology and their association with biological markers. J Path 1995; 176(4): 333-41
• Yagata H, Hariaga K, Suzuki M et al. Comedonecrosis is an unfavorable marker in node negative invasive breast carcinoma. Pathol Int 2003; 53(8):501-6
• Egeblad M, Jattela M. Cell death induced by TNF or serum starvation is indepent of erbB receptor signaling in MCF-7 breast carcinoma cells. Int J Cancer 2000;86(5): 617-25
• Adebamowo CA, Ogundiran A, Kang EE, et al. Somatic p53 and HER-2/neu in Nigerian breast cancer. Proc Am Clin Oncol 2003;22:885