ASSESSMENT OF THE POTENTIAL ROLE OF CANDIDATE GENESTHAT MAY BE INVOLVED IN HERCEPTIN TREATMENT RESISTANCE INBREAST CANCER PATIENTS.

Fatma Abdullah Nasr Elwy


Abstract


Breast cancer is the second most common malignancy worldwide and the most frequent cancer in women. A slight majority of cases were in developing countries as Egypt rather than developed world. Worldwide, breast cancer is the fifth cause of malignancy death overall.Breast carcinomas are heterogeneous group of tumors which differ morphologically and at the molecular level.HER-2-positive BC is the most aggressive subtype of BC, where the patient has a decreased overall survival and may have differential responses to a variety of chemotherapeutic and hormonal agents. In the HER-2-positive patients, using therapeutic reagents that target the human epidermal growth factor receptor-2 (HER-2) has improved the outcomes in combination with chemotherapy. PI3K signalling pathway, the downstream signalling for HER-2, is frequently activated in cancer and highly investigated due to its predicted role in the resistance of anti-HER-2 targeted therapy. Missense mutations in PIK3CA and /or loss of PTEN protein expression are described as a main cause of PI3K pathway activation. Although many preclinical and clinical studies confirmed the correlation between PIK3CA mutation and /or PTEN loss and T resistance in HER-2-positive breast cancer, there is no adequate proof to suggest routine genotyping of PIK3CA or PTEN protein expression in clinical practice.Hence, this genetically study was done to estimate the frequencies ofPIK3CAand PTEN mutations andPTEN lossand there correlation with clinical data and overall survival in HER-2-positive patients. Aim of the work: The objective of the present study was to investigate PIK3CA andPTENgene mutations and PTEN protein level in HER2-positive breast cancer patients and to correlate these variables with clinicopathological data and overall survival of the patients. Methods: • Formalin fixed paraffin embedded (FFPE) sections were collected from 51 female Egyptian patients, who were diagnosed with HER-2 positive breast cancer between 2007 and 2013 in the National Cancer Institute in cooperation with the Early Cancer Detection Unit of Ain Shams University Maternity Hospital. • Genomic DNA was extracted.DNA yield and purity was quantitated and assessed using the Nanodrop. • Polymerase chain reaction (PCR) was performed for all DNA samples to amplify PIK3CA (exons 9 and 20) and PTEN (exons 5, 6 and 7). • Gel electrophoresis was performed to detect of the PCR product. • The PCR products were sequenced by Sanger sequencing. • The resulted sequences were compared to human genomic DNA sequence that present in the GenBank using the BLASTsoftware. Mutations and SNPs numbers were identified using ENSEMBL and COSMIC (Catalogue of Somatic Mutations in Cancer)databases. • Immunohistochemistry (IHC) technique was performed to detect PTEN protein level in 16 out of 51cases. • Statistical analysis was done to investigate the correlation between mutations and protein status and clinicopathological data on overall survival of patients.


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Other Titles تقييم الدور المحتمل للجينات المرشحة التى قدتشاركفى مقاومة العلاج بالهيرسيبتين فى مرضى سرطان الثدى
Issue Date 2017
URI http://research.asu.edu.eg/handle/12345678/2573


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