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
Departament of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas, Av. Limeira 901, CP 52, Areão, Piracicaba, CEP SP, Brazil.
Virchows Arch. 2008 Jul;453(1):57-67. doi: 10.1007/s00428-008-0626-5. Epub 2008 Jun 6.
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.
本研究旨在调查非恶性口腔上皮以及口腔或头颈部鳞状细胞癌（OSCC/HNSCC）中脂肪酸合酶（FAS）和表皮生长因子受体2（ErbB2）的表达情况。采用免疫组织化学方法评估形态学正常、角化过度、发育异常的口腔上皮以及高分化和低分化OSCC中的FAS、ErbB2和Ki-67。还在含有55例HNSCC的组织芯片中分析了这些蛋白。利用SCC-9细胞研究分化过程中的FAS和ErbB2。FAS在角化过度、发育异常和OSCC中的表达高于正常上皮。高分化OSCC/HNSCC中FAS阳性率高于低分化肿瘤。在非恶性和高分化OSCC/HNSCC角质形成细胞表面以及低分化细胞的细胞质中观察到ErbB2。Ki-67指数从正常口腔上皮到OSCC逐渐升高，与细胞表面ErbB2呈负相关，与细胞质内ErbB2呈正相关。最后，通过锚定剥夺法诱导SCC-9细胞分化后，细胞膜上ErbB2阳性细胞增多。总之，FAS在OSCC/HNSCC和角化过度的口腔上皮中过表达，ErbB2在分化的角质形成细胞表面和低分化肿瘤细胞的细胞质中表达。上皮发育异常和OSCC中的Ki-67指数高于形态学正常的口腔上皮。
