Clinicopathological significance of ubiquitin-specific protease 2a (USP2a), fatty acid synthase (FASN), and ErbB2 expression in oral squamous cell carcinomas

Autor(es)

da Silva, Sabrina Daniela ^{[1, 2]} ; Cunha, Isabela Werneck ^[3] ; Nishimoto, Ines Nobuko ^[1] ; Soares, Fernando Augusto ^[3] ; Carraro, Dirce Maria ^[4] ; Kowalski, Luiz Paulo ^[1] ; Graner, Edgard ^[2]

Afiliação do(s) autor(es)

^[1] AC Camargo Hosp, Dept Head & Neck Surg & Otorhinolaryngol, BR-01509900 Sao Paulo - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Sch Dent Piracicaba, Dept Oral Diag, BR-13414018 Sao Paulo - Brazil

^[3] AC Camargo Hosp, Dept Anat Pathol, BR-01509900 Sao Paulo - Brazil

^[4] AC Camargo Hosp, Mol Biol Lab, BR-01509900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Oral Oncology; v. 45, n. 10, p. E134-E139, OCT 2009.
• Citações Web of Science: 23

Resumo

Overexpression of fatty acid synthase (FASN) and ErbB2 has been described in oral squamous cell carcinomas (OSCC). FASN is the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids and its expression can be regulated by ErbB2. The deubiquitinating enzyme (DUB) ubiquitin-specific protease 2a (USP2a) plays a critical role in prostate cancer cell survival by stabilizing the FASN protein. This study investigates whether the gene expression and the immunohistochemical status of FASN, ErbB2, and USP2a correlate with the clinicopathological characteristics of OSCC cases. A strong positive correlation among ErbB2, FASN, and USP2a expression (p = 0.001) was observed by qRT-PCR in laser capture micro-dissected OSCC samples. Perineural infiltration was associated with ErbB2 mRNA expression (p = 0.046). The presence of metastatic cervical lymph nodes was associated with FASN (p = 0.002), ErbB2 (p = 0.001), and USP2a (p = 0.006) mRNA levels. ErbB2 staining at the cell membranes was stronger in well-differentiated lesions while a cytoplasmic positivity was found in poorly differentiated tumors. Most of the OSCC (97.06%) that showed a high positivity for FASN were also labeled for ErbB2 at the cell membranes (p = 0.001). FASN and ErbB2 positivity was associated with tumor thickness and lymphatic embolization (p = 0.006 and p = 0.035, p = 0.006 and p = 0.024 respectively). The membrane expression of ErbB2 as well as FASN and Ki-67 staining were significantly associated with a high risk of recurrence by predicting both disease free survival (log-rank test, p = 0.0056, p = 0.0011, and p = 0.0004, respectively) and overall survival (log-rank test, p = 0.0005, p = 0.0062, and p = 0.0001, respectively). Taken together, the results presented here suggest a molecular connection among FASN, ErbB2, and USP2a in OSCC since their mRNA and protein levels were associated with tumor progression and poor prognosis. (C) 2009 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 02/08030-1 - Estudo das enzimas desubiquitinantes Ubp-45(USP9) e Ubp-69 (USP2) no controle da proliferação de linhagens celulares de carcinoma bucal e de fibromatose gengival hereditária
• Beneficiário: Edgard Graner
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/06398-7 - Analise da expressao da isopeptidase usp2a e seu substrato, acido graxo sintetase (fas), em carcinomas espinocelulares da regiao de cabeca e pescoco.
• Beneficiário: Sabrina Daniela da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado