الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Breast cancer is the second most common malignancy in females worldwide. In Egypt, a registry- based cancer study starting from 2008 ending on 2011 has shown that breast cancer accounts for 33.6% of cases. Multiple studies concerning biologic behavior of invasive breast carcinoma have been carried out in order to identify patients who may suffer from poor clinical outcome. Among the studied parameters are markers of tumour proliferation. These include Ki-67 and the novel marker pituitary derived tumour-transforming growth protein (PTTG).
Ki-67 is a nuclear protein which role in cell-cycle requires extensive research. Ki-67 expression is associated with worse disease free survival and better response to chemotherapy. However; Ki-67 routine use in clinical practice requires further validation. Securin (nuclear form of PTTG) is a proto-oncogene whose protein product is responsible for regulating sister chromatids separation during mitosis. Overexpression of securin was detected in a range of endocrine and non-endocrine tumours including breast carcinoma. It was found to be associated with aggressive tumour behaviour, recurrence and distant metastasis.
The aim of the present work was to check the immunohistochemical value of securin expression in comparison to ki-67 in invasive breast carcinoma as a marker of proliferation and to check the effect of combined expression on clinical outcome.
In this retrospective case control study, 145 patients were managed by modified radical mastectomy and adjuvant therapy. They were classified based on clinical outcome into two groups. The first group included invasive breast carcinoma patients whom were disease free and the second group included patients who developed either recurrence or distant metastasis at the end of 24 months follow up duration.
Histopathologic examination of primary tumour sections of the cases was performed in order to assess histologic type, histologic grade according to Nottingham Grading System, presence of in situ carcinoma and lymphovascular invasion. Pathologic staging of the cases was performed according to TNM staging system 7th edition.
During histopathologic examination, two areas were selected from each tumour section for tissue microarray construction. Six tissue microarray paraffin blocks including two hundred and ninety cores representative of study material were constructed and their sections were placed on coated slides. Immunohistochemical staining of tissue microarray sections was performed for HER-2, Ki-67 and securin. HER-2 scoring was performed according to 2013 ASCO/CAP guidelines and recommendations. Evaluation of Ki-67 and securin was carried out by simple semiquantitative assessment and digital image analysis using ImmunoRatio® plugin. Molecular subtyping was performed using estrogen receptors (ER), progesterone receptors (PR), obtained from immunohistochemistry reports issued from pathology department, HER-2 and Ki-67 according to 2011 St. Gallen consensus recommendations.
Only 118 cases had representative and interpretable tissue cores. The first group included 77 patients and the second group included 41 patients. In the current study, the risk association assessment using Mann Whitney U test revealed no relation between age and clinical outcome.
Risk association assessment between a range of clinicopathological parameters and the clinical outcome using chi square test was carried out. Those include tumour size, histologic type, histologic grade, in situ component, lymphovascular invasion, nodal status, extranodal extension, hormonal receptor status, HER-2 status and molecular subtypes. Only lymphovascular invasion, nodal status, extranodal extension, estrogen receptors, HER-2 status and molecular subtypes showed significant risk association with poor clinical outcome.
Ki-67 labelling indices obtained by semiquanitative assesssment were significantly higher in the second group using Mann-Whitney U test (p=0.006*), unlike Ki-67 labelling indices obtained by ImmunoRatio®.
Comparison between labelling indices of Ki-67 obtained by both methods showed statistically significant difference. Nevertheless, labelling indices acquired by both methods had overall good agreement (Cronbach’s alpha coefficient=0.786).
Securin labelling indices acquired by both semiquantitative assessment and image analysis were significantly higher in the second group. Agreement between both means of scoring was fair (Cronbach’s alpha coefficient=0.637).
Receiver Operator characteristics (ROC) analysis was used to evaluate the diagnostic accuracy of Ki-67 and securin scoring by semiquantitative assessment and ImmunoRatio®. ROC analysis for Ki-67 labelling