ErbB receptors and fatty acid synthase expression in aggressive head and neck squamous cell carcinomas.
CONCLUSIONS
Overexpression of ErbB receptors is frequent in head and neck squamous cell carcinomas (HNSCC) and seems to be correlated with tumor progression and metastasis. Fatty acid synthase (FASN), the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids, is regulated by ErbB2 and overexpressed in several human malignancies.


METHODS
This study was performed to examine the immunohistochemical expression patterns of ErbB1, ErbB2, ErbB3, ErbB4, and FASN in a tissue microarray, containing 33 representative areas from aggressive primary HNSCC (whose patients had distant metastasis), and 21 matched lung metastasis.


RESULTS
Strong correlation among the expression of ErbB family receptors was found (ErbB1-ErbB2 P = 0.008, ErbB1-ErbB4 P = 0.018, EbB2-ErbB3 P = 0.001, ErbB2-ErbB4 P = 0.006, ErbB3-ErbB4 P=0.012) in the HNSCC. FASN expression was significantly associated with ErbB2 (P = 0.024). Lymphatic permeation was correlated with ErbB3 (P = 0.033) and histological grade with ErbB4 staining (P = 0.050). ErbB1 and ErbB2 were found mainly in patients with smoking habit (P = 0.011 and P = 0.027), and ErbB2 was associated with alcohol consumption and clinical stage (P = 0.014 and P = 0.031). Finally, FASN was overexpressed in lung metastasis, in comparison with matched HNSCC samples (P = 0.006).


CONCLUSIONS
The results showed that high FASN immunohistochemical expression is a feature of HNSCC lung metastasis, and ErbB1-ErbB2, ErbB1-ErbB4, ErbB2-ErbB3, ErbB2-ErbB4, and ErbB3-ErbB4 expression levels are correlated in the respective primary tumors, being ErbB2 the preferred coexpression partner of all the other ErbB receptors.
Silva
S D
SD
Department of Head and Neck Surgery and Otorhinolaryngology Anatomic Pathology Thoracic Surgery, A.C. Camargo Hospital, São Paulo, Brazil. sabrina.silva@hcancer.org.br
Cunha
I W
IW
Younes
R N
RN
Soares
F A
FA
Kowalski
L P
LP
Graner
E
E
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000556:secondary; D016022:Case-Control Studies; D018450:Disease Progression; D066246:ErbB Receptors / Q000032:analysis*; D054890:Fatty Acid Synthase, Type I / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D020893:Receptor, ErbB-3 / Q000032:analysis; D066247:Receptor, ErbB-4; D012189:Retrospective Studies; D012907:Smoking; D015996:Survival Rate
D066246:ErbB Receptors; D054890:Fatty Acid Synthase, Type I; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C518729:FASN protein, human; C512478:EGFR protein, human; C587689:ERBB4 protein, human