Characterization of Helicobacter pylori infection, Epstein-Barr virus and gene-protein expression profile in gastric adenocarcinomas

Abstract

Gastric cancer (GC) is one of the most common cancers and remains the second leading cause of cancer mortality worldwide. Several factors can contribute individually or together to their development.The Epstein-Barr virus (EBV) and Helicobacter pylori (HP) infection appear as important risk factors, participating in processes that lead to changes in the gastric mucosa, gastritis development, molecular changes and, consequently, to the GC. The molecular parameters evaluation beside the identification of risk factors has been useful to clear up the carcinogenesis and assist in the prognostic markers determination. The HER-2 oncogene is amplified or over-expressed in several cancers, including GC, which is associated with a worse prognosis in carcinomas such as breast and lung. It also presents importance as a biomarker to identify responsive patients to therapy using trastuzumab monoclonal antibody. Similarly, microsatellites are considered phenotypic markers of prognosis and therapeutic response, making the identification of patients with mutations in the DNA repair genes (mismatch repair genes - MMR) assumes great importance in the neoplastic process understanding. It is believed that the identification of parameters that reflect the biological behavior of GC and the characterization of risk factors associated with its development are determining factors in the prognosis and increment of cancer therapy. The objective of this study is to determine the frequency of HP and EBV infection in GC patients from Cancer Institute of São Paulo State (ICESP) and characterize the population profile for genetic variables HER-2 and MMR, analyzing them in conjunction with clinicopathological parameters, including age, gender, tumor type, level of tumor invasion, lymph node status, pathologic stage, characterization of mucin profile, relation with other biomarkers and clinical impact. A retrospective review of patients submitted to gastrectomy for gastric adenocarcinoma in the institution in the period 2009 to 2014 will be conducted through immunohistochemical methods and in situ hybridization (ISH) from the construction of tissue microarrays (tissue microarray - TMA) with viable tumor samples obtained from each patient paraffin blocks. The results of this study will be analyzed according to prognosis and survival, showing the impact of the categories evaluated in the survival curves of our patients. (AU)