河南食管癌高发区食管癌及癌旁组织AnnexinⅡ表达失调变化

Dysregulation of Annexin Ⅱ Expression in Esophageal Squamous Cell Cancer and Adjacent Tissues from a High-Incidence Area for Esophageal Cancer in Henan Province

背景与目的:作者对河南食管癌高发区正常人和食管癌患者蛋白质组差异蛋白分析发现AnnexinⅡ是主要差异候选蛋白之一。本研究通过分析该地区食管鳞癌(esophageal squamous cell carcinoma,ESCC)及癌旁形态学正常食管上皮(normal epithelium,NOR)、基底细胞过度增生(basal cell hyperplasia,BCH)、不典型增生(dysplasia,DYS)和原位癌(carcinoma in situ,CIS)中AnnexinⅡ动态表达状况,探讨AnnexinⅡ在ESCC癌变过程中的作用及机制。方法:采用ABC免疫组织化学法分析了河南食管癌高发区33例ESCC手术标本和癌旁NOR,以及BCH、DYS和CIS中AnnexinⅡ蛋白表达变化;另应用RT-PCR方法检测了ESCC手术标本和癌旁NOR中AnnexinⅡ mRNA差异表达情况。结果:在90.6%的NOR中有AnnexinⅡ蛋白表达,免疫染色评分≥4,随着病变加重其表达下降,CIS时AnnexinⅡ蛋白完全失表达的比例达到了50.0%。高分化SCC时AnnexinⅡ蛋白表达又升高,而后随着SCC失分化表达逐渐降低,低分化SCC中45.4%病灶AnnexinⅡ失表达。但RT-PCR并没有检测到NOR和SCC中AnnexinⅡ mRNA的差异表达。结论:AnnexinⅡ表达增强或降低可能与癌前病变逆转或进展相关,并有可能成为高危人群筛查及食管癌早期诊断的分子指标。

BACKGROUND ＆ OBJECTIVE：Our recent study on proteomics for esophageal cancer has indicated the importance of Annexin Ⅱ as a promising protein to distinguish esophageal cancer patients from healthy subjects. This study was to detect the expression of Annexin Ⅱ in esophageal squamous cell carcinoma （ESCC） and adjacent tissues, and to explore the role of Annexin Ⅱ in ESCC pathogenesis and mechanisms. METHODS. The expression of Annexin Ⅱ in 33 specimens of ESCC and adjacent tissues from Linzhou, a high-incidence area for esophageal cancer in Henan province, was detected by ABC immunohistochemistry and reverse transcription- polymerase chain reaction （RT-PCR）. RESULTS： Annexin Ⅱ protein was expressed in 90.6% normal esophageal epithelium and decreased with ESCC progression. In carcinoma in situ （CIS）, 50.0% foci lost Annexin Ⅱ protein expression. The expression of Annexin Ⅱ protein was increased in well differentiated SCC and decreased with loss of differentiation of SCC. In poorly differentiated SCC, 45.4% foci lost Annexin Ⅱ protein expression. However, RT-PCR didn＇t detect differential expression of Annexin Ⅱ mRNA between normal esophageal epithelium and CIS. CONCLUSIONS. Elevated or reduced expression of Annexin Ⅱ may be correlated to reverse or progression of carcinogenesis respectively, and Annexin Ⅱ may be another candidate biomarker for screening of high-risk subjects and early diagnosis of SCC.