Miyawaki Michiyo, Hijiya Naoki, Tsukamoto Yoshiyuki, Nakada Chisato, Kawahara Katsunobu, Moriyama Masatsugu
Department of Surgery II, Oita University Faculty of Medicine, Oita, Japan.
APMIS. 2008 Dec;116(12):1097-106. doi: 10.1111/j.1600-0463.2008.01125.x.
This study aimed to determine whether epidermal growth factor receptor (EGFR), which has been reported to be frequently overexpressed in esophageal carcinoma cells, is actually activated in the cells. Paraffin-embedded specimens of 39 cases of esophageal carcinoma were analyzed immunohistochemically with anti-EGFR polyclonal antibody (alpha-EGFR Ab) and also an anti-phospho-EGFR-specific polyclonal antibody (alpha-p-EGFR(Tyr992) Ab) that specifically recognizes phosphorylated tyrosine 992 of EGFR. All of the 39 cases were found to express EGFR, but the expression levels were not significantly higher than those in basal cells of the normal esophageal epithelium. In 38 of the 39 cases, alpha-p-EGFR(Tyr992) immunoreactivity was evident. Interestingly, the positively stained carcinoma cells were not distributed diffusely, and strongly immunostained cells tended to be localized in areas of severe dysplasia and in microinvasive foci just adjacent to the main invasive carcinoma. However, the deeply invasive front never exhibited positive immunoreactivity. The present findings suggest that phosphorylation of EGFR( Tyr992) may play some specific functional role in esophageal carcinomas besides promotion of cell proliferation.
本研究旨在确定表皮生长因子受体(EGFR)在食管癌细胞中是否真正被激活,此前有报道称其在食管癌细胞中经常过度表达。用抗EGFR多克隆抗体(α-EGFR抗体)以及抗磷酸化EGFR特异性多克隆抗体(α-p-EGFR(Tyr992)抗体)对39例食管癌石蜡包埋标本进行免疫组织化学分析,α-p-EGFR(Tyr992)抗体可特异性识别EGFR的磷酸化酪氨酸992。结果发现,所有39例病例均表达EGFR,但其表达水平并不显著高于正常食管上皮基底细胞中的表达水平。在39例病例中的38例中,α-p-EGFR(Tyr992)免疫反应明显。有趣的是,阳性染色的癌细胞并非弥漫性分布,强免疫染色细胞倾向于局限在重度发育异常区域以及紧邻主要浸润癌的微浸润灶中。然而,深度浸润前沿从未显示出阳性免疫反应。目前的研究结果表明,EGFR(Tyr992)的磷酸化除了促进细胞增殖外,可能在食管癌中发挥一些特定的功能作用。