Clinicopathological significance of ubiquitin-specific protease 2a (USP2a), fatty acid synthase (FASN), and ErbB2 expression in oral squamous cell carcinomas.
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 microdissected 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.
Department of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Av. Limeira 901, CP52, Areão, Piracicaba, CEP 13414-018, São Paulo, Brazil. sabrina.silva@hcancer.org.br
Sabrina Daniela
SD
da Silva
Isabela Werneck
IW
Cunha
Inês Nobuko
IN
Nishimoto
Fernando Augusto
FA
Soares
Dirce Maria
DM
Carraro
Luiz Paulo
LP
Kowalski
Edgard
E
Graner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D010450:Endopeptidases / Q000378:metabolism*; D064429:Fatty Acid Synthases / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D064570:Ubiquitin-Specific Proteases
D010450:Endopeptidases; D064429:Fatty Acid Synthases; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D064570:Ubiquitin-Specific Proteases; C508053:ERBB2 protein, human