AbstractsBiology & Animal Science

Expression of cyclin D1 and its correlation with p27KIP1 in non-neoplastic and non-dysplastic mucosa, oral epithelial dysplasia and oral squamous cell carcinoma

by Guangzhao Guan




Institution: University of Otago
Department:
Year: 0
Keywords: CyclinD1; P27; oral; cancer
Record ID: 1316529
Full text PDF: http://hdl.handle.net/10523/5125


Abstract

Background Oral and pharyngeal cancer accounts for one-sixth of the total cancers worldwide. An estimated 263,900 new cases and 128,000 deaths from oral cavity cancer (including lip cancer) occurred in 2008 worldwide. Smoking, alcohol use, smokeless tobacco products, and HPV infections are the major risk factors for head and neck cancers, with smoking and alcohol having synergistic effects. Squamous cell carcinoma of the oral cavity is driven by a multistep process of accumulation of genetic mutations related to cell proliferation and differentiation. Increasing evidence suggests that cyclins, cyclin dependent kinases (CDKs), and cyclin dependent kinases inhibitors (CDKIs) either are themselves targets for genetic change in cancer or are disrupted secondarily by other oncogenic events. Cyclin D1 and p27KIP1 are two important regulators for the cell cycle G1/S checkpoint. Normally, cyclin D1 at G1 is constant or at a very low level and its excessive expression may be associated with disordered proliferation of cells leading to malignant change. On the other hand, p27KIP1 is an anti-oncogene and under the regulation of TGF-β, p27KIP1 inhibits activity of oncogenes and controls the transition of G1/S phase mainly by the interaction with CDK and CDK-Cyclin, so as to inhibit cell proliferation and give cells opportunities to repair DNA. No study, to date, has clearly determined the expression of cyclin D1 and its correlation with in p27KIP1 in non-neoplastic and non-dysplastic mucosa, oral dysplasia, and oral squamous cell carcinoma. Aim The purpose of this research is to determine cyclin D1 and p27KIP1 intensity of expression, location and pattern in oral epithelial dysplasia and oral squamous cell carcinoma by standard immunohistochemistry. Methodology Formalin-fixed, paraffin-embedded (FFPE) tissue biopsies of the oral mucosa with a diagnosis of non-neoplastic tissue (Gingivitis) (n=10), oral epithelial dysplasia (mild and moderate)(n=12) and oral squamous cell carcinoma (n=11) for the period from 2005 to 2013 were obtained from the histopathology-archived records of the University of Otago, School of Dentistry, Medlab Dental Oral Pathology Diagnostic Laboratory. All the specimens were prepared and stained using immunohistochemistry following confirmation of diagnosis on H&E stained sectioned. Scanning software was used to determine cyclin D1 and p27KIP1 intensity of expression, location and pattern. Result A significant increase in expression of cyclin D1 and a decrease in expression of p27KIP1 proteins were observed with the severity of oral epithelial dysplasia and in less well-differentiated OSCC in this study. In the control groups, scattered cells showing cyclin D1 protein expression were seen in the parabasal and basal epithelial layers. In contract to the distribution in the control group, there was a more diffuse distribution of cells showing cyclin D1 protein expression extending from the basal cell layer into the prickle cell layers in epithelial dysplasia. Diffuse distribution of cyclin D1…