Study of genetic and metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by exome, gene expression and immunohistochemistry

• Grant number: 15/07304-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: February 01, 2017
• End date: April 30, 2022
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Fernanda Viviane Mariano Brum Corrêa
• Grantee: Fernanda Viviane Mariano Brum Corrêa
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• City of the host institution: Campinas
• Associated researchers: Albina Messias de Almeida Milani Altemani ; Luciana Souto Mofatto ; Luiz Lehmann Coutinho ; Luiz Paulo Kowalski ; Marcelo Falsarella Carazzolle ; Oslei Paes de Almeida ; Ricardo Della Coletta
• Associated scholarship(s): 20/08431-4 - METABOLOMIC PROFILING ANALYSIS IN THE MALIGNANT TRANSFORMATION OF PLEOMORPHIC ADENOMA, BP.DR; 19/09419-0 - Genomic alterations in the malignant transformation of the Pleomorphic Adenoma, BP.DR; 20/04127-9 - Study of genetic and metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by exome, gene expression and immunohistochemistry, BP.TT; + associated scholarships 19/10788-0 - MORPHOLOGICAL AND METABOLIC COMPARATIVE STUDY BETWEEN CARCINOMA EX PLEOMORPHIC ADENOMA OF LACRIMAL AND SALIVAR GLANDS, BP.IC; 19/06809-2 - Analysis of mass spectrometry in the malignant transformation of the pleomorphic adenoma. correlation of data with gene expression and exome, BP.MS; 18/25294-0 - Study of genetic and metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by exome, gene expression and immunohistochemistry, BP.TT; 17/13167-1 - Study of metabolic changes of Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma by immunohistochemistry, BP.IC; 17/00831-0 - Study of genetic and metabolic changes of pleomorphic adenoma and carcinoma ex pleomorphic adenoma by exome, gene expression and immunohistochemistry, BP.JP - associated scholarships

Abstract

The pleomorphic adenoma (PA) is the most common tumor of the salivary gland and although benign, it has chances of recurrence and malignant transformation to carcinoma ex pleomorphic adenoma (CXPA). The latter is an aggressive neoplasm occurring with metastasis and death in a large percentage of cases. Although both tumors have important discoveries in genetic and molecular areas, the changes found are focal and in specific genetic sites. There are still many questions about the diagnostic market, pathogenesis and target therapy of PA and CXPA. In this project, we will study a group of PAs and CXPAs (subdivided according to histological type and degree of progression) through the complete sequencing of the exome (Whole Exome Sequencing - WES) and added the findings to prior results from our group by array-CGH technique.We will do validation of these reactions (exome and array-CGH) by Sanger sequencing and after we will analyse the candidate genes through gene expression. Thus, with our work, we will extend the individual genetic knowledge on PAs and CXPAs, and we will still be able to compare the copy number alterations and mutations acquired in benign counterpart and that are conserved in carcinoma, as well as new unique events of the malignant tumor, trying to do correlaction with progression and histopathological subtype. Since the pathogenesis of cancer is characterized by a complex mix of genetic and metabolic changes, we will also study various metabolic pathways (glucogenesis, lipogenesis) through immunohistochemical markers, gene expression and we will investigate the exome and array-CGH findings searching relation with these pathways. With this broad approach, analyzing genetic and metabolic changes involved in tumorigenesis PA, CXPA carcinogenesis and tumor progression, we intend to add significant knowledge to what is known today expecting to discovery markers for diagnosis, pathogenesis and target therapy. (AU)

Scientific publications

(30)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

DOS SANTOS, ERISON S.; RAMOS, JOAB C.; NORMANDO, ANA GABRIELA C.; MARIANO, V, FERNANDA; PAES LEME, ADRIANA F.. Epigenetic alterations in salivary gland tumors. ORAL DISEASES, JAN 2020. (15/07304-0, 18/19922-9, 17/00831-0)

LIMA-SOUZA, REYDSON ALCIDES DE; SCARINI, JOAO FIGUEIRA; EGAL, ERIKA SAID ABU; CRESCENCIO, LIVIA RAMALHO; COSTA, JEZREEL CORRE DA; SILVA, MARIO FERNANDEZ SOBRAL; TINCANI, ALFIO JOSE; GONDAK, ROGERIO OLIVEIRA; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Secretory carcinoma ex pleomorphic adenoma of the submandibular gland: An immunohistochemical study. Oral Oncology, v. 120, SEP 2021. (19/06809-2, 15/07304-0, 19/09419-0)

SPERANDIO, MARCELO; WARNAKULASURIYA, SAMAN; SOARES, ANDRESA BORGES; PASSADOR-SANTOS, FABRICIO; MARIANO, FERNANDA VIVIANE; PASSOS LIMA, CARMEN SILVIA; SCARINI, JOAO FIGUEIRA; LOPES DOMINGUETE, MATHEUS HENRIQUE; MORAES, PAULO DE CAMARGO; MARTINS MONTALLI, VICTOR ANGELO; et al. Oral epithelial dysplasia grading: Comparing the binary system to the traditional 3-tier system, an actuarial study with malignant transformation as outcome. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. N/A, p. 8-pg., 2022-10-13. (17/06579-1, 15/07304-0)

SCARINI, JOAO FIGUEIRA; ROSA, LARISSA FERNANDES; DE LIMA SOUZA, REYDSON ALCIDES; ABU EGAL, ERIKA SAID; TINCANI, ALFIO JOSE; MARTINS, ANTONIO SANTOS; KOWALSKI, LUIZ PAULO; GRANER, EDGARD; DELLA COLETTA, RICARDO; CARLOS, ROMAN; et al. Gene and immunohistochemical expression of HIF-1 alpha, GLUT-1, FASN, and adipophilin in carcinoma ex pleomorphic adenoma development. ORAL DISEASES, v. 26, n. 6, APR 2020. (15/07304-0, 17/00831-0, 17/13167-1)

DE LIMA-SOUZA, REYDSON ALCIDES; RODRIGUES, NATALIA DE MAGALHAES; SCARINI, JOAO FIGUEIRA; SOBRAL SILVA, MARIO FERNANDEZ; TINCANI, ALFIO JOSE; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Metabolic alterations in carcinoma ex pleomorphic adenoma development of lacrimal glands. INTERNATIONAL OPHTHALMOLOGY, NOV 2021. (19/06809-2, 19/10788-0, 15/07304-0, 19/09419-0)

DAMAS, INGRID IARA; LAVAREZE, LUCCAS; SCARINI, JOAO FIGUEIRA; DE LIMA-SOUZA, REYDSON ALCIDES; EMERICK, CAROLINA; GONCALVES, MAYARA TREVIZOL; FIGUEIREDO-MACIEL, TAYNA; VIEIRA, GUSTAVO DE SOUZA; KIMURA, TALITA DE CARVALHO; AQUINO, IARA GONCALVES; et al. Immunopathological insights into villitis of unknown etiology on the basis of transplant immunology. Placenta, v. 131, p. 9-pg., 2023-01-01. (19/09419-0, 20/08431-4, 15/07304-0)

SCARINI, JOAO FIGUEIRA; DE LIMA-SOUZA, REYDSON ALCIDES; LAVAREZE, LUCCAS; EMERICK, CAROLINA; MIYAOK, RAFAELLA DINI; SCHIAVON KINASZ, LETICIA RAYSA; MAUNSELL, REBECCA; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Oral Teratoma with Hairy Polyp-Like Features: A Brief Report of a Rare Presentation. INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY, v. N/A, p. 4-pg., 2022-11-03. (21/12567-1, 15/07304-0, 19/09419-0, 19/06809-2)

PULIDO DIAZ, KATYA; GONDAK, ROGERIO; MARTINS, LEANDRO LIPORONI; DE ALMEIDA, OSLEI PAES; LEON, JORGE ESQUICHE; MARIANO, FERNANDA VIVIANE; ALTEMANI, ALBINA; VARGAS, PABLO AGUSTIN. Fatty acid synthase and Ki-67 immunoexpression can be useful for the identification of malignant component in carcinoma ex-pleomorphic adenoma. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. 48, n. 3, p. 232-238, MAR 2019. (15/07304-0, 12/10781-7)

SOARES, CIRO DANTAS; DE LIMA MORAIS, THAYNA MELO; CARLOS, ROMAN; MARTINS, MANOELA DOMINGUES; DE ALMEIDA, OSLEI PAES; MARIANO, FERNANDA VIVIANE; ALTEMANI, ALBINA. Immunohistochemical expression of mammaglobin in salivary duct carcinomas de novo and salivary duct carcinoma ex pleomorphic adenoma. HUMAN PATHOLOGY, v. 92, p. 59-66, OCT 2019. (15/07304-0, 17/00831-0, 15/25905-1, 17/16102-8)

MARIANO, FERNANDA VIVIANE; FIDALGO, FELIPE; MAION CASARIM, ANDRE LUIS; MARTINS, ANTONIO SANTOS; SCARINI, JOAO FIGUEIRA; DE LIMA SOUZA, REYDSON ALCIDES; EGAL, ERIKA SAID; KOWALSKI, LUIZ PAULO; VICTORINO KREPISCHI, ANA CRISTINA; ALTEMANI, ALBINA. Somatic copy number alterations in pleomorphic adenoma and recurrent pleomorphic adenoma. ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY, v. 129, n. 1, p. 59-64, JAN 2020. (15/07304-0, 17/00831-0, 11/23204-5, 11/23366-5)

SCARINI, JOAO FIGUEIRA; ABU EGAL, ERIKA SAID; DE LIMA-SOUZA, REYDSON ALCIDES; CRESCENCIO, LIVIA RAMALHO; EMERICK, CAROLINA; KOWALSKI, LUIZ PAULO; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Two sides of the same coin: Insights into the myoepithelial cells in carcinoma ex pleomorphic adenoma development. CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, v. 157, JAN 2021. (15/07304-0, 17/00831-0, 17/13167-1)

KIMURA, TALITA DE CARVALHO; DE LIMA-SOUZA, REYDSON ALCIDES; SCARINI, JOAO FIGUEIRA; LAVAREZE, LUCCAS; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Clinicopathological profile of sclerosing polycystic adenoma/adenosis: A systematic review. HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, v. N/A, p. 9-pg., 2023-07-05. (15/07304-0, 19/09419-0, 20/08431-4)

GONCALVES, JUSSARA MARIA; SCARINI, JOAO FIGUEIRA; GONDAK, ROGERIO; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Oral involvement of sinonasal undifferentiated carcinoma: A case report and immunohistochemical study of a challenging case. Oral Oncology, v. 126, p. 3-pg., 2022-02-18. (15/07304-0, 19/09419-0)

ABU EGAL, ERIKA SAID; SCARINI, JOAO FIGUEIRA; DE LIMA-SOUZA, REYDSON ALCIDES; LAVAREZE, LUCCAS; FERNANDES, PATRICIA MARIA; EMERICK, CAROLINA; GONCALVES, MAYARA TREVIZOL; HELMS, MY N.; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Tumor microenvironment in salivary gland carcinomas: An orchestrated state of chaos. Oral Oncology, v. 127, p. 11-pg., 2022-02-18. (17/00831-0, 19/09419-0, 17/13167-1, 19/06809-2, 15/07304-0)

DE ANGELIS, CAMILA MATSUNAGA; DE LIMA-SOUZA, REYDSON ALCIDES; SCARINI, JOAO FIGUEIRA; ABU EGAL, ERIKA SAID; DO AMARAL-SILVA, GLEYSON KLEBER; GONDAK, ROGERIO DE OLIVEIRA; DE ALMEIDA, OSLEI PAES; CHONE, CARLOS TAKAHIRO; KOWALSKI, LUIZ PAULO; ALTEMANI, ALBINA; et al. Immunohistochemical Expression of Fatty Acid Synthase (FASN) is Correlated to Tumor Aggressiveness and Cellular Differentiation in Salivary Gland Carcinomas. Head and Neck Pathology, v. 15, n. 4, p. 8-pg., 2021-04-11. (15/07304-0, 19/09419-0)

SCARINI, JOAO FIGUEIRA; SABINO, WELLINGTON LIMA; DE LIMA-SOUZA, REYDSON ALCIDES; ABU EGAL, ERIKA SAID; TINCANI, ALFIO JOSE; GONDAK, ROGERIO; KOWALSKI, LUIZ PAULO; KREPISCHI, ANA CRISTINA VICTORINO; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Distinct copy number signatures between residual benign and transformed areas of carcinoma ex pleomorphic adenoma. SCIENTIFIC REPORTS, v. 14, n. 1, p. 10-pg., 2024-10-09. (19/09419-0, 15/07304-0, 17/00831-0, 21/12567-1)

KIMURA, TALITA DE CARVALHO; DE LIMA-SOUZA, REYDSON ALCIDES; LAVAREZE, LUCCAS; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Clinicopathological analysis of hybrid carcinomas of the salivary glands: A systematic review. JOURNAL OF STOMATOLOGY ORAL AND MAXILLOFACIAL SURGERY, v. 126, n. 5, p. 8-pg., 2024-12-17. (20/08431-4, 15/07304-0, 22/11861-6)

SCARINI, JOAO FIGURIRA; ALMEIDA MARIZ, BRUNO AUGESTO LINHARES; DE LIMA-SOUZA, REYDSON ALCIDES; LAVAREZE, LUCCAS; EMERICK, CAROLINA; TINCANI, ALFIO JOSE; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVANE. Spindle cell carcinoma of the lip: An immunohistochemical study of a challenging case. Oral Oncology, v. 125, p. 3-pg., 2022-02-01. (19/06809-2, 15/07304-0, 19/09419-0, 18/24715-2)

DE ANGELIS, CAMILA MATSUNAGA; DE LIMA-SOUZA, REYDSON ALCIDES; SCARINI, JOAO FIGUEIRA; ABU EGAL, ERIKA SAID; DO AMARAL-SILVA, GLEYSON KLEBER; GONDAK, ROGERIO DE OLIVEIRA; DE ALMEIDA, OSLEI PAES; CHONE, CARLOS TAKAHIRO; KOWALSKI, LUIZ PAULO; ALTEMANI, ALBINA; et al. Immunohistochemical Expression of Fatty Acid Synthase (FASN) is Correlated to Tumor Aggressiveness and Cellular Differentiation in Salivary Gland Carcinomas. Head and Neck Pathology, APR 2021. (15/07304-0, 19/09419-0)

SCARINI, JOAO FIGUEIRA; LAVAREZE, LUCCAS; DE LIMA-SOUZA, REYDSON ALCIDES; EMERICK, CAROLINA; GONCALVES, MAYARA TREVIZOL; FIGUEIREDO-MACIEL, TAYNA; VIEIRA, GUSTAVO DE SOUZA; KIMURA, TALITA DE CARVALHO; DE SA, RAISA SALES; AQUINO, IARA GONCALVES; et al. Head and neck squamous cell carcinoma: Exploring frontiers of combinatorial approaches with tyrosine kinase inhibitors and immune checkpoint therapy. CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, v. 180, p. 14-pg., 2022-12-01. (15/07304-0, 21/12567-1, 19/09419-0, 19/06809-2)

LAVAREZE, LUCCAS; SCARINI, JOAO FIGUEIRA; LIMA-SOUZA, REYDSON ALCIDES DE; EGAL, ERIKA SAID ABU; TETZNER, DIEGO; LEITE, AMANDA ALMEIDA; VARGAS, PABLO AGUSTIN; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Granulomatous gingival enlargement in a patient with an unrecognized HIV infection. JOURNAL OF THE AMERICAN DENTAL ASSOCIATION, v. 154, n. 7, p. 5-pg., 2023-07-01. (15/07304-0, 19/06809-2, 19/09419-0)

DE LIMA-SOUZA, REYDSON ALCIDES; SCARINI, JOAO FIGUEIRA; LAVAREZE, LUCCAS; EMERICK, CAROLINA; DOS SANTOS, ERISON SANTANA; PAES LEME, ADRIANA FRANCO; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Protein markers of primary salivary gland tumors: A systematic review of proteomic profiling studies. ARCHIVES OF ORAL BIOLOGY, v. 136, p. 13-pg., 2022-02-15. (19/06809-2, 18/19922-9, 19/09419-0, 15/07304-0)

LAVAREZE, LUCCAS; SCARINI, JO AO FIGUEIRA; DE LIMA-SOUZA, REYDSON ALCIDES; EMERICK, CAROLINA; DE SA, RAISA SALES; AQUINO, IARA GONCALVES; FERNANDES, PATRICIA MARIA; GONCALVES, MAYARA TREVIZOL; HELMS, MY N.; ALTEMANI, ALBINA; et al. Salivary gland cancer in the setting of tumor microenvironment: Translational routes for therapy. CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, v. 171, p. 10-pg., 2022-03-01. (19/06809-2, 15/07304-0, 19/09419-0)

DE LIMA-SOUZA, REYDSON ALCIDES; SCARINI, JOAO FIGUEIRA; LAVAREZE, LUCCAS; DOMINGUES, ROMENIA RAMOS; LEME, ADRIANA FRANCO PAES; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Malignant phenotype acquisition in pleomorphic adenoma: An exclusive proteins analysis. ORAL DISEASES, v. N/A, p. 4-pg., 2023-01-20. (19/09419-0, 15/07304-0, 20/08431-4)

LIMA-SOUZA, REYDSON ALCIDES DE; VIEIRA, GUSTAVO DE SOUZA; KIMURA, TALITA DE CARVALHO; SCARINI, JOAO FIGUEIRA; LAVAREZE, LUCCAS; MACIEL, TAYNA FIGUEIREDO; GONCALVES, MOISES WILLIAN APARECIDO; ABU EGAL, ERIKA SAID; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE. Insights into the molecular alterations of PLAG1 and HMGA2 associated with malignant phenotype acquisition in pleomorphic adenoma. CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, v. 204, p. 10-pg., 2024-10-04. (19/09419-0, 23/13091-6, 15/07304-0, 22/07410-9, 20/08431-4, 22/11861-6)

LAVAREZE, LUCCAS; KIMURA, TALITA DE CARVALHO; SCARINI, JOAO FIGUEIRA; DE LIMA-SOUZA, REYDSON ALCIDES; GONCALVES, MOISES WILLIAN APARECIDO; DE SA, RAISA SALES; AQUINO, IARA GONCALVES; FERNANDES, PATRICIA MARIA; RIBEIRO, FERNANDA CRISTINA POSCAI; ALTEMANI, ALBINA; et al. Advances and current concepts on Eph receptors and ephrins in upper digestive tract cancers. FRONTIERS IN ONCOLOGY, v. 14, p. 14-pg., 2025-01-07. (15/07304-0, 19/09419-0, 19/06809-2)

DE SOUZA VIEIRA, GUSTAVO; DE CARVALHO KIMURA, TALITA; SCARINI, JOAO FIGUEIRA; DE LIMA-SOUZA, REYDSON ALCIDES; LAVAREZE, LUCCAS; EMERICK, CAROLINA; GONCALVES, MAYARA TREVIZOL; DAMAS, INGRID IARA; FIGUEIREDO-MACIEL, TAYNA; DE SA, RAISA SALES; et al. Hematopoietic colony-stimulating factors in head and neck cancers: Recent advances and therapeutic challenges. CYTOKINE, v. 173, p. 17-pg., 2023-11-07. (19/09419-0, 20/08431-4, 15/07304-0, 21/12567-1)

SCARINI, JOAO FIGUEIRA; GONCALVES, MOISES WILLIAN APARECIDO; DE LIMA-SOUZA, REYDSON ALCIDES; LAVAREZE, LUCCAS; DE CARVALHO KIMURA, TALITA; YANG, CHING-CHU; ALTEMANI, ALBINA; MARIANO, FERNANDA VIVIANE; SOARES, HELOISA PRADO; FILLMORE, GARY CHRIS; et al. Potential role of the Eph/ephrin system in colorectal cancer: emerging druggable molecular targets. FRONTIERS IN ONCOLOGY, v. 14, p. 14-pg., 2024-04-02. (19/09419-0, 19/06809-2, 15/07304-0)

DE LIMA-SOUZA, REYDSON ALCIDES; KIMURA, TALITA DE CARVALHO; SCARINI, JOAO FIGUEIRA; LAVAREZE, LUCCAS; MACIEL, TAYNA FIGUEIREDO; DAMAS, INGRID IARA; HARA, LAURA WACHTER; MESQUITA, ALESSANDRA DE SOUSA; SIMIONATO, ANA VALERIA COLNAGHI; MARTINEK, PETR; et al. Discovery metabolomics and genetic analysis reveal lipid pathway alterations associated with malignant phenotype acquisition in pleomorphic adenoma and a novel NTF3::ITPR2 fusion in carcinoma ex pleomorphic adenoma. Virchows Archiv, v. N/A, p. 13-pg., 2025-10-13. (23/13091-6, 19/09419-0, 23/01150-8, 22/11861-6, 15/07304-0, 20/08431-4)

DOS SANTOS, ERISON S.; RAMOS, JOAB C.; NORMANDO, ANA GABRIELA C.; MARIANO, FERNANDA, V; PAES LEME, ADRIANA F.. Epigenetic alterations in salivary gland tumors. ORAL DISEASES, v. 26, n. 8, p. 9-pg., 2020-01-22. (15/07304-0, 17/00831-0, 18/19922-9)