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

• Grant number: 16/25524-0
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2018
• End date: July 31, 2019
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Ulysses Ribeiro Júnior
• Grantee: Ulysses Ribeiro Júnior
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: André Roncon Dias ; Marcus Fernando Kodama Pertille Ramos ; Marina Alessandra Pereira ; Osmar Kenji Yagi

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)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEREIRA, MARINA ALESSANDRA; DE CASTRIA, TIAGO BIACHI; KODAMA PERTILLE RAMOS, MARCUS FERNANDO; DIAS, ANDRE RONCON; CARDILI, LEONARDO; RODRIGUES MORAES, RAFAEL DYER; ZILBERSTEIN, BRUNO; NAHAS, SERGIO CARLOS; RIBEIRO JR, ULYSSES; DE MELLO, EVANDRO SOBROZA. Cytotoxic T-lymphocyte-associated protein 4 in gastric cancer: Prognosis and association with PD-L1 expression. JOURNAL OF SURGICAL ONCOLOGY, v. 124, n. 7, JUL 2021. (16/25524-0)

PEREIRA, MARINA ALESSANDRA; KODAMA PERTILLE RAMOS, MARCUS FERNANDO; DIAS, ANDRE RONCON; FARAJ, SHEILA FRIEDRICH; RIBEIRO E RIBEIRO, RENAN; DE CASTRIA, TIAGO BIACHI; ZILBERSTEIN, BRUNO; FERREIRA ALVES, VENANCIO AVANCINI; RIBEIRO JR, ULYSSES; DE MELLO, EVANDRO SOBROZA. Expression Profile of Markers for Targeted Therapy in Gastric Cancer Patients: HER-2, Microsatellite Instability and PD-L1. MOLECULAR DIAGNOSIS & THERAPY, v. 23, n. 6, p. 761-771, DEC 2019. (16/25524-0)

KODAMA PERTILLE RAMOS, MARCUS FERNANDO; PEREIRA, MARINA ALESSANDRA; DE MELLO, EVANDRO SOBROZA; CIRQUEIRA, CINTHYA DOS SANTOS; ZILBERSTEIN, BRUNO; FERREIRA ALVES, VENANCIO AVANCINI; RIBEIRO-JUNIOR, ULYSSES; CECCONELLO, IVAN. Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization: Analysis in western patients after curative-intent surgery. WORLD JOURNAL OF CLINICAL ONCOLOGY, v. 12, n. 8, p. 688-701, AUG 24 2021. (16/25524-0)

PEREIRA, MARINA A.; DIAS, ANDRE R.; RAMOS, MARCUS F. K. P.; CARDILI, LEONARDO; MORAES, RAFAEL D. R.; ZILBERSTEIN, BRUNO; NAHAS, SERGIO C.; MELLO, EVANDRO S.; RIBEIRO JR, ULYSSES. Gastric cancer with microsatellite instability displays increased thymidylate synthase expression. JOURNAL OF SURGICAL ONCOLOGY, v. 126, n. 1, p. 9-pg., 2022-07-01. (16/25524-0)

PEREIRA, MARINA ALESSANDRA; RAMOS, MARCUS FERNANDO KODAMA PERTILLE; DIAS, ANDRE RONCON; RIBEIRO, RENAN; CARDILI, LEONARDO; ZILBERSTEIN, BRUNO; CECCONELLO, IVAN; RIBEIRO, JR., ULYSSES; DE MELLO, EVANDRO SOBROZA; DE CASTRIA, TIAGO BIACHI. Scoring systems for PD-L1 expression and their prognostic impact in patients with resectable gastric cancer. Virchows Archiv, v. 478, n. 6, p. 1039-1048, JUN 2021. (16/25524-0)

KODAMA PERTILLE RAMOS, MARCUS FERNANDO; PEREIRA, MARINA ALESSANDRA; CARDILI, LEONARDO; DE MELLO, EVANDRO SOBROZA; RIBEIRO JR, ULYSSES; ZILBERSTEIN, BRUNO; CECCONELLO, IVAN. Expression profiles of gastric cancer molecular subtypes in remnant tumors. WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY, v. 13, n. 4, p. 14-pg., 2021-04-15. (16/25524-0)

RAMOS, MARCUS FERNANDO KODAMA PERTILLE; PEREIRA, MARINA ALESSANDRA; DE CASTRIA, TIAGO BIACHI; RIBEIRO E RIBEIRO, RENAN; CARDILI, LEONARDO; DE MELLO, EVANDRO SOBROZA; ZILBERSTEIN, BRUNO; RIBEIRO-JUNIOR, ULYSSES; CECCONELLO, IVAN. Remnant gastric cancer: a neglected group with high potential for immunotherapy. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, v. 146, n. 12, JUL 2020. (16/25524-0)

RAMOS, MARCUS F. K. P.; PEREIRA, MARINA A.; AMORIM, LARISSA C.; DE MELLO, EVANDRO S.; FARAJ, SHEILA F.; RIBEIRO JR, ULYSSES; HOFF, PAULO M. G.; CECCONELLO, IVAN; DE CASTRIA, TIAGO B.. Gastric cancer molecular classification and adjuvant therapy: Is there a different benefit according to the subtype?. JOURNAL OF SURGICAL ONCOLOGY, v. 121, n. 5, DEC 2019. (16/25524-0)

PEREIRA, MARINA ALESSANDRA; KODAMA PERTILLE RAMOS, MARCUS FERNANDO; DIAS, ANDRE RONCON; FARAJ, SHEILA FRIEDRICH; CIRQUEIRA, CINTHYA DOS SANTOS; DE MELLO, EVANDRO SOBROZA; ZILBERSTEIN, BRUNO; FERREIRA ALVES, VENANCIO AVANCINI; RIBEIRO, JR., ULYSSES. Immunohistochemical expression of thymidylate synthase and prognosis in gastric cancer patients submitted to fluoropyrimidine-based chemotherapy. CHINESE JOURNAL OF CANCER RESEARCH, v. 30, n. 5, p. 526-536, OCT 2018. (16/25524-0)