Hwang Emily Ya-Chi, Yu Chuan-Hang, Cheng Shih-Jung, Chang Julia Yu-Fong, Chen Hsin-Ming, Chiang Chun-Pin
Harvard School of Dental Medicine, Boston, MA, USA.
J Oral Pathol Med. 2009 Jan;38(1):87-93. doi: 10.1111/j.1600-0714.2008.00664.x. Epub 2008 Mar 18.
The epithelial cell adhesion molecule (Ep-CAM) is involved in cell signaling, migration, proliferation, cell-cycle regulation, and cancer metastasis.
This study used an immunohistochemical technique to examine the expression of Ep-CAM protein in 84 specimens of oral squamous cell carcinoma (OSCC), 98 specimens of oral epithelial dysplasia (OED, 31 mild, 41 moderate, and 26 severe OED cases), and 15 specimens of normal oral mucosa (NOM).
We found that the mean Ep-CAM labeling indices (LIs) decreased significantly from NOM (80 +/- 18%) and mild OED (76 +/- 14%) through moderate OED (66 +/- 22%) and severe OED (55 +/- 20%) to OSCC samples (46 +/- 16%, P < 0.001). A significant correlation was found between the lower mean Ep-CAM LI and OSCCs with larger tumor size (P = 0.003), positive lymph node metastasis (P = 0.022), more advanced clinical stages (P < 0.001), cancer recurrence (P = 0.021), or extracapsular spread of lymph node (P = 0.015). However, only Ep-CAM LI < 50% (P < 0.0001) was identified as an independent unfavorable prognosis factor by multivariate analyses with Cox proportional hazard regression model. Kaplan-Meier curve showed that OSCC patients with an Ep-CAM LI < 50% had a significantly poorer cumulative survival than those with an Ep-CAM LI > or = 50% (P < 0.00001, log-rank test).
We conclude that the decreased expression of Ep-CAM protein is an early event in oral carcinogenesis. The Ep-CAM LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.
上皮细胞粘附分子（Ep-CAM）参与细胞信号传导、迁移、增殖、细胞周期调控及癌症转移。
本研究采用免疫组织化学技术检测84例口腔鳞状细胞癌（OSCC）标本、98例口腔上皮发育异常标本（31例轻度、41例中度和26例重度口腔上皮发育异常病例）及15例正常口腔黏膜（NOM）标本中Ep-CAM蛋白的表达。
我们发现，Ep-CAM标记指数（LI）的平均值从正常口腔黏膜（80±18%）和轻度口腔上皮发育异常（76±14%），经中度口腔上皮发育异常（66±22%）和重度口腔上皮发育异常（55±20%），至口腔鳞状细胞癌标本（46±16%）显著降低（P<0.001）。Ep-CAM平均LI较低与肿瘤体积较大的口腔鳞状细胞癌（P = 0.003）、阳性淋巴结转移（P = 0.022）、更晚期临床分期（P<0.001）、癌症复发（P = 0.021）或淋巴结包膜外扩散（P = 0.015）之间存在显著相关性。然而，通过Cox比例风险回归模型进行多变量分析，仅Ep-CAM LI<50%（P<0.0001）被确定为独立的不良预后因素。Kaplan-Meier曲线显示，Ep-CAM LI<50%的口腔鳞状细胞癌患者的累积生存率显著低于Ep-CAM LI≥50%的患者（P<0.00001，对数秩检验）。
我们得出结论，Ep-CAM蛋白表达降低是口腔癌发生的早期事件。口腔鳞状细胞癌标本中的Ep-CAM LI可预测口腔鳞状细胞癌的进展及患者的生存情况。
