Kanczuga-Koda Luiza, Wincewicz Andrzej, Fudala Andrzej, Abrycki Tomasz, Famulski Waldemar, Baltaziak Marek, Sulkowski Stanislaw, Koda Mariusz
Department of Pathology, Maria Sklodowska-Curie Memorial Bialystok Oncology Center, Bialystok, Poland.
Department of Anatomy, Faculty of Health Sciences, Jan Kochanowski Memorial University, Kielce, Poland.
Oncol Lett. 2014 Jun;7(6):1863-1870. doi: 10.3892/ol.2014.1970. Epub 2014 Mar 14.
The majority of solid cancers present with qualitative and quantitative aberrations of adhesion proteins, including E-cadherin and β-catenin, and connexin (Cx) gap junction proteins, which is consistent with alterations in the expression and location of such proteins in neoplastic cells. Since there are no data on the correlation between adhesion proteins and Cxs in human colorectal cancer (CRC), the aim of the present study was to evaluate the expression and correlation between these proteins. Tissue specimens were obtained from 151 cases of surgically removed colorectal adenocarcinomas. The samples were examined by immunohistochemistry with the use of antibodies against E-cadherin, β-catenin and the three Cxs: Cx26, Cx32 and Cx43. The aberrant expression of the studied adhesion proteins (primarily cytoplasmic for E-cadherin and cytoplasmic and/or nuclear for β-catenin) was observed, whereas only a minority of cases revealed normal membranous distribution of the labeling. The present study is the first in the literature to reveal a correlation between the expression of E-cadherin and β-catenin and the examined Cxs in CRC in humans. The positive correlation between the Cxs, particularly Cx26 and Cx32, and the adhesive proteins occurred in patients without lymph node metastases and in the moderately differentiated tumors (G2). Such a dependency was not observed in the analysis of the correlation between Cx43 and E-cadherin. However, a positive correlation between these proteins was observed in patients with lymph nodes metastases. Additionally, a link between the expression of these adhesion proteins was observed. The present study indicates, for the first time, that the expression of adhesion proteins, E-cadherin and β-catenin, is closely associated with the expression of three studied Cxs in CRC, and that this correlation may improve an understanding of the carcinogenic process in this cancer.
大多数实体癌都存在黏附蛋白的定性和定量异常,包括E-钙黏蛋白和β-连环蛋白,以及连接蛋白(Cx)间隙连接蛋白,这与这些蛋白在肿瘤细胞中的表达和定位改变是一致的。由于目前尚无关于人类结直肠癌(CRC)中黏附蛋白与连接蛋白之间相关性的数据,本研究的目的是评估这些蛋白之间的表达及相关性。从151例手术切除的结直肠腺癌病例中获取组织标本。使用针对E-钙黏蛋白、β-连环蛋白和三种连接蛋白(Cx26、Cx32和Cx43)的抗体,通过免疫组织化学对样本进行检测。观察到所研究的黏附蛋白存在异常表达(E-钙黏蛋白主要为细胞质表达,β-连环蛋白为细胞质和/或细胞核表达),而只有少数病例显示标记物呈正常膜分布。本研究是文献中首次揭示人类结直肠癌中E-钙黏蛋白和β-连环蛋白的表达与所检测的连接蛋白之间存在相关性。连接蛋白,尤其是Cx26和Cx32,与黏附蛋白之间的正相关出现在无淋巴结转移的患者以及中度分化肿瘤(G2)中。在分析Cx43与E-钙黏蛋白之间的相关性时未观察到这种依赖性。然而,在有淋巴结转移的患者中观察到了这些蛋白之间的正相关。此外,还观察到了这些黏附蛋白表达之间的联系。本研究首次表明,黏附蛋白E-钙黏蛋白和β-连环蛋白的表达与结直肠癌中三种所研究的连接蛋白的表达密切相关,并且这种相关性可能有助于增进对该癌症致癌过程的理解。