Evaluation of the Relationship Between HER2 and CDK12 Mutation Status and Histopathological and Clinical Findings in Bladder Cancer
Project no. 30830 · Status: Kapanmış (Yayın bekleniyor) · 2023
Summary
<p>The most common cancer in the bladder is urothelial carcinoma, which is usually non-invasive or early invasive at the time of diagnosis. At diagnosis, muscle-invasive disease, distant metastasis, and the presence of variant histology are associated with a poor prognosis. The Human Epidermal Growth Factor Receptor 2 (HER2) is a transmembrane tyrosine kinase receptor. Cyclin-Dependent Kinase 12 (CDK12) is a serine/threonine protein kinase that belongs to the cyclin-dependent kinase family and plays roles in various cellular functions, including transcription, post-transcriptional DNA damage response, and stress response. Amplification of HER2 and CDK12 has been identified in many malignancies.</p><p>In our study, approximately 400 cases (age range 18-90) who underwent radical cystectomy at Ege University Hospital between 2000-2021 will be reviewed by retrieving their hematoxylin-eosin stained slides from the archive. Immunohistochemical analysis of CDK12 and HER2 will be conducted on 3-5 micron thick sections prepared from the selected suitable blocks.</p><p>According to previous studies, CDK12 shows nuclear expression, so only nuclear staining in tumor cells will be considered as positive expression. The staining intensity and percentages of CDK12 will be evaluated using the modified Allred scoring system. HER2 expression will be investigated immunohistochemically, and the percentage and intensity of membranous staining will be assessed according to the ASCO/CAP guidelines for breast cancer.</p><p>While CDK12 and HER2 amplification have been associated with prognosis in various tumors such as breast, gastric, and ovarian cancers, data on urothelial carcinomas are quite limited.</p><p>In our study, the presence of HER2 and CDK12 mutations will be evaluated immunohistochemically in cases diagnosed with muscle-invasive urothelial carcinoma at Ege University Faculty of Medicine, Department of Medical Pathology. The relationship between these mutations and clinical and histopathological features such as stage, histological subtype, and survival will be investigated.</p>