الفهرس 
Embryological Background
Clinical BackgroundOnly 14 pages are availabe for public view
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Abstract
Ovarian carcinoma is one of the leading causes of death in patients with gynecological malignancy. Ovarian carcinomas represent about 175 of all carcinomas of the female genital organs. Surface epithelial tumors form two thirds of ovarian neoplasms. In Egypt, tumors of the female genital system represent 2915 of total malignancies, ovarian cancer representing 19105 of them. Surface epithelial tumors represent 019115 of ovarian tumors. Ovarian surface epithelial tumors are classified to the following histological subtypes: serous, mucinous, endometrioid, clear cell, transitional cell, squamous, mixed, and undifferentiated. Usually each subtype can be classified as benign, borderline, and malignant
Immunohistochemistry has become an important tool in the diagnosis, prognosis and possibly in the therapy targeted towards several tumors. Many tumor suppressor genes are implicated in the behavior of ovarian cancer and can be studied immunohistochemically. These include the Her 2 neu gene which is a proto-oncogene located on chromosome 10 that encodes a membrane tyrosine kinase growth factor receptor. The prognostic and predictive importance of this receptor has been demonstrated in many malignancies and its study has led to the development of targeted therapies especially in patients who develop tolerance or poor response to chemotherapy.The aim of this study is to evaluate the immunohistochemical protein expression of the oncogene Her2 in the borderline and malignant surface epithelial ovarian tumors main types (i.e. serous, mucinous & endometrioid) and to compare and detect their association with different clinicopathologic parameters and investigate the possibility of the use of Her2 neu oncogene in their prognosis and identifying positive cases (patients) that may benefit from targeted therapy.
Our study material was comprised of retrospectively collected random sample composed of 1%0 archived formalin fixed paraffin embedded representative tumor tissue blocks (our sample) of previously diagnosed borderline and malignant ovarian surface epithelial tumors with their main subtypes (serous, mucinous and endometrioid) received between 2772 to 2717.
Revision of H&E slides of each case was done to select the proper blocks for our study. Each paraffin block was cut into 1-2 m thick sections, mounted on glass slides, deparaffinized by xylene, rehydrated by descending grades of alcohol then stained using hematoxylin and eosin. Pathology reports and slides were reviewed.
More sections were cut on positively charged glass slides and treated by ready to use monoclonal mouse Her 2 antibody (C- erbB2 clone CB 11) using the manufacturer’s protocol instructions.
The Her 2 level of overexpression was based on a scale from 7–1+, in which 7 represented no reactivity and 1+ represented the highest level of reactivity. The tumor tissue was judged as having a score of 1+ when the membrane staining was observed in 175 of the tumor cells but not in a complete circumscribed fashion or weak intensity. A score of 2+ was given if 175 of the tumor cells demonstrated circumscribed membrane staining of moderate intensity, and a score of 1+ was given if 175 of the tumor cells showed circumscribed membrane staining of strong intensity.
Her 2/neu is overexpressed in %915 of EOTs, with more expression in high age groups (over %7 years) and with small sizes unilateral tumors. Her 2/ neu is overexpressed in malignant tumors rather than borderline ones, as .292 % of positive cases were malignant. Serous tumors showed overexpression more than other tumor types. Her 2 neu over expression increase with high grade tumors, as 005 of positive cases were grade II- grade III. Also recurrent cases showed higher expression than tumors of first presentation. EOTs coexisting with SUC showed a significant increase in Her2 neu over expression predicting an underlying molecular genetic defect causing this association.
So we may suggest that Her2neu assessment should be done on more sample sizes or population based studies with correlation to more clinicopathologic features and prognostic factors, but it can be considered as routine test in all EOCs that is planned to receive treatment, not responding to chemotherapy, suffering tumor relapse or developed tolerance to different drugs. We suggest it may be used in conjunction with other adjuvant methods such FISH, SISH or CISH for gene amplification assesment.