Differential expression of fatty acid synthase (FAS) and ErbB2 in nonmalignant and malignant oral keratinocytes

• Published in: Virchows Archiv : an international journal of pathology 2008-07, Vol.453 (1), p.57-67
• Main Authors: Silva, Sabrina D., Cunha, Isabela W., Rangel, Ana Lúcia C. A., Jorge, Jacks, Zecchin, Karina G., Agostini, Michelle, Kowalski, Luiz P., Coletta, Ricardo D., Graner, Edgard
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Epithelium - metabolism; Fatty Acid Synthases - genetics; Fatty Acid Synthases - metabolism; Fatty acids; Female; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Investigative techniques, diagnostic techniques (general aspects); Keratinocytes - cytology; Keratinocytes - metabolism; Keratinocytes - pathology; Male; Medical sciences; Medicine; Medicine & Public Health; Mouth - cytology; Mouth - metabolism; Mouth - pathology; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Original Article; Otorhinolaryngology. Stomatology; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-008-0626-5

The aim of this study was to investigate fatty acid synthase (FAS) and ErbB2 expression in nonmalignant oral epithelium and oral or head and neck squamous cell carcinomas (OSCC/HNSCC). Morphologically normal, hyperkeratotic, and dysplastic oral epithelium as well as well-differentiated and poorly differentiated OSCC were immunohistochemically evaluated for FAS, ErbB2, and Ki-67. These proteins were also analyzed in a tissue microarray with 55 HNSCC. SCC-9 cells were used to study FAS and ErbB2 during differentiation. FAS expression was higher in hyperkeratosis, dysplasias, and OSCC than in normal epithelium. Well-differentiated OSCC/HNSCC were more positive for FAS than the poorly differentiated tumors. ErbB2 was observed at the surface of nonmalignant and well-differentiated OSCC/HNSCC keratinocytes and in the cytoplasm of poorly differentiated cells. Ki-67 index was progressively higher from normal oral epithelium to OSCC, inversely correlated with cell surface ErbB2, and positively correlated with intracytoplasmic ErbB2. Finally, SCC-9 cell cultures were enriched in membrane ErbB2-positive cells after differentiation by anchorage deprivation. In conclusion, FAS is overexpressed in OSCC/HNSCC and hyperkeratotic oral epithelium and ErbB2 is found at the cell surface of differentiating keratinocytes and in the cytoplasm of poorly differentiated tumor cells. Ki-67 index is higher in epithelial dysplasias and OSCC than in morphologically normal oral epithelium.