Silva Sabrina D, Perez Danyel E, Alves Fabio A, Nishimoto Inês N, Pinto Clóvis A L, Kowalski Luiz P, Graner Edgard
Department of Oral Diagnosis, School of Dentistry of Piracicaba, University of Campinas, Av. Limeira 901, CP52, Areão, Piracicaba, CEP 13414-018, São Paulo, Brazil.
Oral Oncol. 2008 May;44(5):484-90. doi: 10.1016/j.oraloncology.2007.06.008. Epub 2007 Sep 6.
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.
癌蛋白ErbB2（HER-2/neu）是一种酪氨酸激酶细胞表面受体，在包括口腔鳞状细胞癌（OSCC）在内的多种人类恶性肿瘤中过度表达。最近研究表明，ErbB2可调节脂肪酸合酶（FAS）的表达，FAS是一种负责饱和脂肪酸从头生物合成的多功能酶复合物。在此，我们评估了ErbB2、FAS和Ki-67的免疫组化表达与舌鳞状细胞癌（SCC）临床病理特征之间的关系。对1990年至1995年接受治疗的102例舌SCC患者进行了研究。从病历中获取临床和治疗数据，并复查组织病理学特征。将石蜡包埋组织进行ErbB2、FAS和Ki-67的标准免疫组化反应。在舌SCC样本中发现细胞膜上的ErbB2标记与FAS表达之间存在强正相关（p<0.0001）。通过预测无病生存期（对数秩检验，分别为p=0.0096和p=0.0047）和总生存期（对数秩检验，分别为p=0.0029和p=0.0001），ErbB2的胞质表达以及Ki-67核染色均与高复发风险显著相关。综上所述，我们的结果表明，恶性口腔角质形成细胞表面的ErbB2免疫定位与FAS表达相关，而胞质内ErbB2或Ki-67染色可预测舌SCC的高复发风险。
