HER-2/neu overexpression in correlation to Vascular Endothelial Growth Factor ,grade and stage of Non other wised specified Invasive ductal carcinoma

Jabir Neima Al-khafaji, Ali; H. Al-Kelabi, Liwaa; A. AL-Dujaily, Esraa

	HER-2/neu overexpression in correlation to Vascular Endothelial Growth Factor ,grade and stage of Non other wised specified Invasive ductal carcinoma
Al-Qadisiah Medical Journal
Article 1, Volume 6, Issue 2, 2010, Pages 27-37 PDF (0 K)
Authors
Ali Jabir Neima Al-khafaji; Liwaa H. Al-Kelabi; Esraa A. AL-Dujaily
Abstract
Abstract This study aimed to assess the significance of human epidermal growth factor (HER-2/neu) protein overexpression and its possible correlation with vascular endothelial growth factor (VEGF),grade and stage in human non otherwise specified breast cancer. The present investigation was performed over a period starting from November 2008 to January 2009 .Formalin fixed, paraffin-embedded blocks from 30 patients with breast cancer were included in this study. A group of 15 patients with benign breast lesions (fibroadenoma) was included as a comparative group and 15 normal breast tissue sections were included as control group. Labeled Streptavidin-Biotin Complex (LSAB) method was employed for immunohistochemical detection of HER-2/neu. Avidin-Biotin Complex (ABC) method was employed for immunohistochemical detection of VEGF . A total of 30 malignant cases were included.HER2/neu was considered as positive in(18 cases)60% of non otherwise specified invasive ductal carcinoma and VEGF was considered as positive in (21cases)70% with concomitant positivity of both markers in more than half (16 cases)53.3% out of 30 malignant cases . No overexpression of both markers have been noticed in normal or benign (fibroadenoma) breast tissue sections with significant difference from that of malignant cases(P<0.05).We did not find any significant difference between overexpression of both(HER-2/neu and VEGF) in relation to age ,tumor size ,tumor stage and positive or negative lymph node breast cancer cases (P>0.05). However there was positive relation between HER-2/neu overexpression and the grade of tumor (P<0.05) ,while there was no significant difference between VEGF overexpression and the tumor grade(P>0.05).HER-2/neu overexpression was positively correlated with VEGF immunostaining in relation to grade and stage (P<0.05). Based upon the findings of this study, it can be concluded that both HER-2/neu and VEGF play an important role in the pathogenesis of non other wised specified breast cancer and supports the evidence of its role in evolution ,angiogenesis and cell survival of this aggressive tumor . This study recommended that the blocking of both HER-2/neu and VEGF may be a target for blocking the evolution and angiogenesis and hence improving the efficacy of anti-cancer therapy against this aggressive type of breast cancer. Breast cancer is the commonest malignant tumor with more than one million new cases occurring worldwide annually(1). In Iraq, where the population was exposed to high levels of depleted uranium following the first and second Gulf Wars, breast cancer is the most common malignant tumor in females(2). Over the last ten years, there has been a three-fold increase in the incidence of breast cancer, with most of this increase being attributed to a particularly aggressive type of the cancer(3) . This may suggest that breast cancer in Iraqi women may have some biological features that need to be explored.Her-2/neu proto-oncogene amplification and or over expression is one of the most important alterations encountered in breast cancer. HER2/neu proto-oncogene is amplified and or over expressed in approximately 20-25% of invasive primary breast cancers (4-6). An association have been found to exist between amplification and or over expression of HER-2/neu and advanced stage , early relapse, and reduced overall survival (7,8). vascular endothelial growth factor, is believed to be a key mediator of angiogenesis which plays a central role both in local tumor growth and distant metastasis in numerous solid tumors, including breast cancer(9). Activation or overexpression of HER-2/neu is associated with up-regulation of vascular endothelial growth factor (VEGF) in human breast cancer cells in vitro. Preclinical experiments indicate that increased expression of VEGF may in part mediate the biologically aggressive phenotype of HER-2/neu overexpressing human breast cancer(10,11) . Therefore we plan to study the possibility of finding a relation between HER-2/neu and VEGF in one of the most aggressive histological types of breast cancer termed the invasive ductal carcinoma of non other wised specified as a possible explanation for the aggressive behavior of this tumor and hence whether such relation could be used as an objective tool for the early management of these patients with this aggressive type of breast cancer patients.

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