VEGF-A in the Differential Anatomopathological Diagnosis in Biliopancreatic Malignant Neoplasms

• Grant number: 22/09870-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2022
• Effective date (End): October 31, 2023
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Dorotéia Rossi Silva Souza
• Grantee: Marcelly Araujo Ferraz
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Introduction - Biliopancreatic malignant neoplasms are the second leading cause of death from cancer of the digestive tract. Among the main types of cancer of the biliopancreatic system, cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (ACDP) stand out, whose anatomopathological similarities make it difficult to differentiate the primary origin of these diseases. To date, there are no molecular markers to differentiate ACDP from CCA. Vascular endothelial growth factor (VEGF) is essential for vasculogenesis and angiogenesis, in addition to acting on tumor growth and proliferation. VEGF-A receives greater attention for its important role in the regulation of angiogenesis during homeostasis and pathological processes. VEGF is expressed in several types of tumors, including gallbladder tumors. Immunohistochemical staining of VEGF is observed in the cytoplasm and nucleus of CCA cells, as well as cytoplasmic staining in ACDP. In this context, the study of molecular markers that participate in carcinogenic pathways may contribute to the differentiation of biliopancreatic neoplasms. Objective - To analyze the gene and protein expression of VEGF-A in patients with ACDP and CCA, in order to identify a potential differential diagnostic marker for these diseases. Methods - 74 individuals will be studied: 30 patients with CCA, 30 patients with ADCP and 14 controls, being 7 samples of cystic duct from patients with cholelithiasis and 7 samples of pancreatic tissue from necropsy, all without clinical, biochemical and histopathological signs of the aforementioned neoplasms. Clinical data will be obtained from electronic medical records. RNA will be extracted from paraffin tissue samples for analysis of gene expression by real-time polymerase chain reaction (RT-PCR). The protein expression of VEGF-A in tumor tissues will be analyzed by immunohistochemistry and quantified by ImageJ software. In the inferential analysis, the normality of distribution of quantitative variables will be evaluated by the Shapiro-Wilk test. For frequency in relation to the clinical-demographic profile of patients and controls, the chi-square (Ç2) or Fisher's test will be used. Sensitivity and specificity parameters will be evaluated using Receiver Operating Characteristic (ROC), considering areas under the curve e0.7 as clinically relevant. An alpha error of 5% will be allowed.