ErbB2 and fatty acid synthase (FAS) expression in 102 squamous cell carcinomas of the tongue: correlation with clinical outcomes.
The oncoprotein ErbB2 (HER-2/neu) is a tyrosine kinase cell surface receptor overexpressed in several human malignancies, including oral squamous cell carcinoma (OSCC). ErbB2 was recently shown to regulate the expression of fatty acid synthase (FAS), a multifunctional enzyme complex responsible for the de novo biosynthesis of saturated fatty acids. Here we evaluated the relationship between the immunohistochemical expression of ErbB2, FAS, and Ki-67 with the clinicopathologic characteristics of tongue squamous cell carcinoma (SCC). One hundred and two patients with tongue SCC treated from 1990 to 1995 were studied. Clinical and treatment data were obtained from the medical records and histopathological features revised. Paraffin-embedded tissues were submitted to standard immunohistochemical reactions for ErbB2, FAS and Ki-67. A strong positive correlation between ErbB2 labeling at the cell membrane and FAS expression was found in the tongue SCC samples (p<0.0001). The intracytoplasmatic expression of ErbB2 as well as Ki-67 nuclear staining were significantly associated with a high risk of recurrence by predicting both disease free survival (log-rank test, p=0.0096 and p=0.0047, respectively) and overall survival (log-rank test, p=0.0029 and p=0.0001, respectively). Taken together, our results suggest that the immunolocalization of ErbB2 at the cell surface of malignant oral keratinocytes is linked to FAS expression whereas the intracytoplasmatic ErbB2 or Ki-67 staining predict high risk of recurrence of tongue SCC.
Silva
Sabrina D
SD
Department of Oral Diagnosis, School of Dentistry of Piracicaba, University of Campinas, Av. Limeira 901, CP52, Areão, Piracicaba, CEP 13414-018, São Paulo, Brazil.
Perez
Danyel E
DE
Alves
Fabio A
FA
Nishimoto
Inês N
IN
Pinto
Clóvis A L
CA
Kowalski
Luiz P
LP
Graner
Edgard
E
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D064429:Fatty Acid Synthases / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D018734:Genes, erbB-2 / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome