title: Activation of sonic hedgehog signaling in oral squamous cell carcinomas: a preliminary study.
abstract: Sonic hedgehog signaling is important for human development, and aberrant regulation of this pathway can result in the development of tumors. The aim of this study was to examine the expression of sonic hedgehog signaling molecules in oral squamous cell carcinoma. By quantitative real-time polymerase chain reaction, the expression of SHH, SMO, PTCH-1, and GLI-1 was analyzed in 30 oral squamous cell carcinoma cases and 8 samples of nonneoplastic oral mucosa and associated to clinical pathologic features. The expression of β-catenin, cyclin D1, Wnt-1, and Egfr was evaluated by immunohistochemistry in 26 available cases of oral squamous cell carcinoma. Normal oral mucosa from healthy individuals was negative for all genes that were evaluated. SHH, PTCH-1, SMO, and GLI-1 were not expressed in nonneoplastic oral mucosa, and low levels of GLI-1 were observed in nonneoplastic oral mucosa that was adjacent to the tumor. All oral squamous cell carcinoma cases expressed high levels of PTCH-1, SMO, and GLI-1 and were devoid of SHH. The expression of SMO was associated with clinical stage (P = .022) and a borderline association in cervical lymph node metastasis (P = .053). PTCH-1 expression showed a strong correlation with SMO (rs = 0.64; P < .001) and GL-1 (rs = 0.70; P < .001); SMO and GLI-1 also correlated with each other (rs, 0.55; P < .001). All proteins evaluated were expressed as cyclin D1 (92% of samples), β-catenin (73%), Egfr (46%), or Wnt-1 (32%). Our data demonstrate that sonic hedgehog signaling is activated in oral squamous cell carcinoma and suggest that this pathway mediates its tumorigenesis.
authors.affiliation: Department of Anatomical Pathology, Hospital A.C. Camargo, 01509-900 São Paulo, Brazil. mebuim@hotmail.com
authors.forename: Marcilei Eliza
authors.initials: ME
authors.lastname: Cavicchioli Buim
authors.forename: Clarissa Araújo S
authors.initials: CA
authors.lastname: Gurgel
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Gonçalves Ramos
authors.forename: Silvia Vanessa
authors.initials: SV
authors.lastname: Lourenço
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D053823:Hedgehog Proteins; C509239:SHH protein, human