title: The sonic hedgehog signaling pathway contributes to the development of salivary gland neoplasms regardless of perineural infiltration.
abstract: The pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) are common tumors arising from salivary glands whose histopathology is heterogeneous. The sonic hedgehog signaling pathway (Hh) and signal transducer and activator of transcription 3 (STAT3) play important roles in cell proliferation, favoring tumor growth. The aim of this investigation was to study components of the Hh pathway, as well as STAT3 in salivary gland neoplasms in an attempt to add information about the biological characteristics of these neoplasms. We used 9 cases of PA, 17 cases of ACC, and 20 cases of MEC. Using immunohistochemistry, SHH, GLI1, SUFU, HHIP, and STAT3 were investigated. For comparative purposes, MCM3 (cellular proliferation marker) was also included. In PA, there was high expression of cytoplasmic SHH and SUFU and low expression of STAT3 and MCM3. In the ACC, there was high expression of GLI1, HHIP, and STAT3 and low expression of SHH, SUFU, and MCM3. In the MEC, we observed high expression of SHH, GLI1, SUFU, and HHIP and low expression of STAT3 and MCM3. There was a statistically significant difference between SHH (p = 0.0064), STAT3 (p = 0.0003), and MCM3 (p = 0.0257) when all tumors were compared and a higher expression in parenchyma for all tumors when stroma and parenchyma were compared (p < 0.05). These findings suggests a possible role of Hh pathway in the development and maintenance of the cytoarchitectural pattern of PA, ACC, and MEC, as well as the participation of STAT3 in the development of ACC, irrespective perineural infiltration.
authors.affiliation: Postgraduate Program in Human Pathology, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.
authors.forename: Manuela Torres Andion
authors.initials: MT
authors.lastname: Vidal
authors.affiliation: A.C. Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Sílvia Vanessa
authors.initials: SV
authors.lastname: Lourenço
authors.affiliation: A.C. Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Postgraduate Program in Human Pathology, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.
authors.forename: Clarissa Araújo
authors.initials: CA
authors.lastname: Gurgel
authors.affiliation: Department of Pathology and Forensic Medicine, School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil.
authors.forename: Eduardo J B
authors.initials: EJ
authors.lastname: Studart
authors.affiliation: Postgraduate Program in Human Pathology, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.
authors.forename: Ludmila de Faro
authors.initials: Lde F
authors.lastname: Valverde
authors.affiliation: Postgraduate Program in Human Pathology, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.|Department of Pathology and Forensic Medicine, School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil.
authors.forename: Iguaracyra Barreto de Oliveira
authors.initials: IB
authors.lastname: Araújo
authors.affiliation: Postgraduate Program in Human Pathology, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.
authors.forename: Eduardo Antônio Gonçalves
authors.initials: EA
authors.lastname: Ramos
authors.affiliation: Laboratory of Oral Surgical Pathology, School of Dentistry, Federal University of Bahia, Salvador, Bahia, Brazil.
authors.forename: Flávia Caló de Aquino
authors.initials: FC
authors.lastname: Xavier
authors.affiliation: Postgraduate Program in Human Pathology, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil. jeanunes@ufba.br.|Laboratory of Oral Surgical Pathology, School of Dentistry, Federal University of Bahia, Salvador, Bahia, Brazil. jeanunes@ufba.br.|Laboratório de Patologia Cirúrgica, UFBA, Avenida Araújo Pinho, 62, Canela, Salvador, Bahia, Brazil, 40110-150. jeanunes@ufba.br.
authors.forename: Jean Nunes
authors.initials: JN
authors.lastname: Dos Santos
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D050796:STAT3 Transcription Factor / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology*; D012469:Salivary Glands / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D050796:STAT3 Transcription Factor
keywords: Hedgehog proteins; Minichromosome maintenance complex component 3; STAT transcription factors; Salivary gland tumors