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الكشف عن طفر الجين عامل النمو البشراوي الثاني (HER2) في سرطان الخلايا الانتقالية باستعمال طريقة اللونية في موقع التهجين == The Detection Of HER2 Gene Mutation In Transitional Cell Carcinoma Using CISH Method
Author name:
عمار عيسى مهدي
Supervisor name:
احمد تركي عبيد | هادي محمد علي الموسوي
General topic:
Medicine
Specific topic:
Clinical Diseases
Degree:
Master
University:
University of Babylon - Faculty Of Medicine - Department Of Diseases
Language:
English
University location:
Babylon
First pages:
19T1130 - p.pdf
Abstract:
يعتبر سرطان المثانة واحدا من اكثر انواع الاورام السرطانية التي تصيب الجهاز البولي حيث انه يعتبر ثاني ورابع الاكثر شيوعا للذكور في العراق والولايات المتحدة على التوالي وايضا يعتبر العاشر والحادي الاكثر شيوعا للاناث في العراق والولايات المتحدة على التوالي. | The urinary bladder cancers are among the common types of cancer of the urinary tract. It is regarded as the second and the fourth most common cancer types for males in Iraq and in the United State of America (USA) respectively and as tenth and eleventh most common cancer types for females in both Iraq and USA respectively. Urothelial Carcinoma is epithelial tumor of urinary bladder (95% of urinary bladder tumor) and it shows wide range of tumor that begins from papilloma and carcinoma in situ to invasive cancer. The patients with urinary bladder cancer that are presented in non - muscle invasive type or muscle invasive type show different rates of HER2 gene amplification (specially for invasive muscle type). Epidermal growth factor receptor (EGFR, also called HER or type I ErbB tyrosine kinase receptors) family is composed of four receptor member which include HER1 (ErbB1 or EGFR), HER2/neu (ErbB2 or C - ErbB2) , ErbB3 ( HER3), and ErbB4 (HER4). HER2/neu protein is glycoprotein produced by HER2 gene which lies in 17q21 (long arm of chromosome 17). This glycoprotein is normally found in lung, breast, urinary bladder, prostate and stomach, and its cytoplasmic portion has enzymatic function (tyrosine kinase activity). This receptor is responsible for the cell survival, normal cell growing and inhibition of apoptosis. HER2/neu protein overexpression is measured by IHC when the result of IHC is equivocal to HER2/neu protein (+ 2). Then, HER2 gene amplification is measured by using an accurate and more practical CISH method. The aims of this study are tried to detect the percentage of HER2 gene amplification in the urothelial carcinoma and distribution of HER2 gene amplification with clinical criteria (age , sex, grade, stage, and location of tumor) of the patients that had urothelial carcinoma of bladder.This study contained retrospective (30 cases) and prospective (20 cases) and was conducted in Al - Hilla Surgical Teaching Hospital and the period of the study extended from October /2015 to August/2016. Clinical data of patients include age, gender , clinical features, and type of bladder biopsy ( endoscopic resection or cystectomy) are taken with paraffin blocks.The practical part of the study was done in the laboratory of the department of pathology / College of Medicine/Babylon university. It included 50 patients with bladder cancer (35 males and 15 females ) with two groups (10 cases is positive and 10 cases is negative). It included 50 patients who were diagnosed with transitional cell carcinoma of urinary bladder with mean age ± SD ( 66.04 ± 10.148 ) years old ranging between 42 - 83 years old. Also, Positive and negative control slides applied with each run CISH method (+ve control of breast tissue that treated by immnohistochemical procedure ( score +3) and the same tissue were applied by removing HER2/neu probe).Fifty patients who were diagnosed with transitional cell carcinoma of bladder and their biopsies of bladder ( taken from endoscopic biopsy or cystectomy). Then, paraffin - embedding procedure was prepared on tissues biopsy and then, hematoxylin and eosin staining (H. and E. staining) procedure was done. Finally, manual CISH was done on both cases(positive and negative cases) and bladder cancer blocks. This CISH method detected her2 amplification according to ASCO/CAP/2013 scoring system. The results showed that age group 61 - 70 years was the highest positive HER2 amplification (64.7%) among other age groups 51 - 60 years (11.8%) and 71 - 80 years old (23.5%), there was a significant association between these age groups with HER2 amplification , p? 0.05. Sex group displayed that 52.9% of male and 47.1% of female who had positive HER2 amplification and there was no significant difference between sex groups with HER2 amplification, p > 0.05. Other results showed that positive HER2 amplification was highest in grade 3 (88.2%) of transitional cell carcinoma when compared to grade 2 (11.8) and grade 1 (0%) and there was significant association between cancer grading system with HER2 amplification, p? 0.05. MIBC and NMIBC of staging cancer system showed 82.4% and 17.6% positive HER2 amplification respectively with a significant difference between them ( p value ? 0.05). Also, other result of the histological types of transitional cell carcinoma revealed 88.2% and 11.8% (positive HER2 amplification) of papillary and flat shape respectively with a significant correlation between them ( p value ? 0.05). The HER2 gene amplification was correlated with grade and stage of bladder carcinoma which showed high amplification in high grade and stage. The HER2 gene amplification was not correlated with the sex of the patients, but more cases of HER2 gene amplification were recorded in males; while there was a correlation with age group specifically (61 - 70 years old). The HER2 gene amplification was associated with aggressive behavior of blabber carcinoma. The CISH method application in HER2 gene amplification was flexible and applical.
