The Association Of Her-2/Neu Overexpression In Relation With P53 Nuclear Accumulation, Hormonal Recceptor Status And Common Clinicopathological Prognostic Parameters In A Series Of Egyptian Women With Inasive Ductal Carcinoma

摘要

Aim of the present study: to determine the association of HER-2eu and p53 as well as hormonal receptor status with conventional common pathologic parameters in invasive ductal carcinoma of breast. Methods: expression of HER-2eu and p53 was examined immunohistochemically and significance was studied in relation with HR status and other clinicopathological parameters. Results: 26%, were positive for HER2, there was a significant association between HER-2 and the accumulation of nuclear p53 (p=0.0017) and the increased size of tumor (p=0.0115) as well as the high grade tumors (p=0.0001) also there was an inverse significant association with ER (p=0.0001) and PR status (p=0.0003) but no significant association as regard number of the invaded LN, tumor necrosis and menopause. Conclusion: Her-2eu may be a powerful predictor of poor prognosis as was directly correlated with p53, tumor size, and grade and inversely correlated with HR status, of breast carcinoma. Introduction Breast cancer is a heterogeneous disease with variable biological and clinical characteristics. The racial influence in invasive breast cancer in terms of age at presentation, clinico-pathological features, and outcome of treatment has been widely reported. It has been established that breast cancer in many Asian and African countries tends to affect younger females, presents in advanced stage with poor prognostic features, and has worse outcome when compared to their counterparts in the Western countries. There is no doubt that the lack of early detection program and awareness contribute to advanced presentation, however, it is unclear why these carcinomas involving young females show higher biological aggressiveness in terms of poor differentiation and lack of steroid receptor expression [1]. Descriptions of prognostic factors in breast cancer have exploded over the past several years. Pathologists have played a major role in identifying different histological and immunohistochemical markers that have a direct bearing on both the treatment and behavior of breast cancer [2]. Besides several prognostic factors like tumor size, histological grade, steroid hormone receptor status, DNA ploidy, or lymph node status, the statues of HER-2eu (human epidermal growth factor receptor 2) probably serves as an additional parameter. HER-2eu proto-oncogene is involved in the regulation of normal cell growth and division and is expressed at low levels in many normal epithelial cells [3]. HER-2eu proto-oncogene encodes an 185KD glycoprotein with tyrosine kinase activity. Over expression of this gene either due to gene amplification and/or increased transcription has been observed in a variety of cancers and has been associated with more aggressive disease and a poor clinical prognosis in 20-30% of patients with breast cancer [4]. Over-expression of HER2eu in breast cancer and certain other tumors appears to correlates with poor survival and to be a central mechanism that may be partly responsible for cellular progression of the neoplastic phenotype; moreover, HER-2eu may potentiate tumorigenesis by inducing tumor cell resistance to host defense mechanisms [5] as it induces resistance to tumor necrosis factor (TNF), which causes cancer cells to escape from host immune defenses [6] and appears to result in reduced sensitivity to immune effectors killing [7]. The aim of this study is to determine the association of HER-2eu over expression in relation with p53 nuclear accumulation, hormonal receptor status as well as conventional common pathologic parameters in a series of Egyptian women with invasive ductal carcinoma of breast. Patients and Methods Fifty tumor samples from patients diagnosed as infiltrating ductal carcinoma were included in the present study, collected from the pathology department, Damanhour Medical Institute, the General Organization for teaching Hospitals and Institutes. All patients had operable tumors with no evidence of distance dissemination