title: High expression of S100A4 and endoglin is associated with metastatic disease in head and neck squamous cell carcinoma.
abstract: The presence of cervical metastasis is responsible for high morbidity and mortality rates in individuals with head and neck squamous cell carcinoma (HNSCC). S100A4, a pleiotropic EF-hand calcium-binding protein, is expressed in various normal and cancer cell types. During cancer progression, molecular disturbances in S100A4 can modulate the activity and expression of pre-metastatic and metastatic genes. In this study, we investigated the association between S100A4 methylation status and protein expression as well as the expression of the S100A4 related-proteins annexin A2 (ANXA2), matrix metallopeptidase-9, and endoglin, for metastasis and other clinicopathological parameters in HNSCC. Formalin-fixed, paraffin-embedded blocks of metastatic and non-metastatic HNSCC and matched cervical lymph node (LN) samples (metastatic LN = mLN, non-metastatic = nmLN, and control LN (lymphadenitis) = cLN) were submitted for methylation specific-polymerase chain reaction and immunohistochemistry. Our results showed that S100A4 methylation status failed to demonstrate association with cervical metastasis and other clinicopathological factors related to HNSCC. HNSCC samples from patients that presented with metastatic disease showed high S100A4 and endoglin expression (p < 0.05). In conclusion, molecular disturbances in S100A4 and endoglin expression might regulate the formation of cervical metastasis in HNSCC.
authors.affiliation: Nucleus of Epidemiological and Molecular Research Catrumano. Health Research Laboratory. Health Science Post-graduate Programme, Universidade Estadual de Montes Claros, Montes Claros, MG, 39401-001, Brazil.
authors.forename: Marcos Vinícius Macedo de
authors.initials: MV
authors.lastname: Oliveira
authors.forename: Carlos Alberto de Carvalho
authors.initials: CA
authors.lastname: Fraga
authors.forename: Lucas Oliveira
authors.initials: LO
authors.lastname: Barros
authors.forename: Camila Santos
authors.initials: CS
authors.lastname: Pereira
authors.forename: Sérgio Henrique Sousa
authors.initials: SH
authors.lastname: Santos
authors.forename: John R
authors.initials: JR
authors.lastname: Basile
authors.forename: Ricardo Santiago
authors.initials: RS
authors.lastname: Gomez
authors.forename: André Luiz Sena
authors.initials: AL
authors.lastname: Guimarães
authors.forename: Alfredo Maurício Batista
authors.initials: AM
authors.lastname: De-Paula
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D000071063:Endoglin; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D009389:Neovascularization, Pathologic; D011956:Receptors, Cell Surface / Q000235:genetics*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human