Second Department of Pathology, University of Athens, Attikon University Hospital, Haidari, Athens, Greece.
Eur J Cancer. 2010 May;46(8):1438-44. doi: 10.1016/j.ejca.2010.01.033. Epub 2010 Feb 23.
Polycomb group (PcG) proteins function as multiprotein complexes and are part of a gene regulatory mechanism that determines cell fate during normal and pathogenic development. Several studies have implicated the deregulation of different PcG proteins in neoplastic progression. Pancreatic ductal adenocarcinoma is an aggressive neoplasm that follows a multistep model of progression through precursor lesions called pancreatic intraepithelial neoplasia (PanIN). Aim of this study was to investigate the role of PcG protein CBX7 in pancreatic carcinogenesis and to evaluate its possible diagnostic and prognostic significance. We analysed by immunohistochemistry the expression of CBX7 in 210 ductal pancreatic adenocarcinomas from resection specimens, combined on a tissue microarray (TMA) including additional 40 PanIN cases and 40 normal controls. The results were evaluated by using receiver operating characteristic (ROC) curve analysis for the selection of cut-off scores and correlated to the clinicopathological parameters of the tumours and the outcome of the patients. Expression of E-cadherin, a protein positively regulated by CBX7, was also assessed. A significantly differential, and progressively decreasing CBX7 protein expression was found between normal pancreatic tissue, PanINs and invasive ductal adenocarcinoma. Loss of CBX7 expression was associated with increasing malignancy grade in pancreatic adenocarcinoma, whereas the maintenance of CBX7 expression showed a trend toward a longer survival. Moreover, loss of E-cadherin expression was associated with loss of CBX7 and with a trend towards worse patient survival. These results suggest that CBX7 plays a role in pancreatic carcinogenesis and that its loss of expression correlates to a more aggressive phenotype.
多梳蛋白（PcG）蛋白作为多蛋白复合物发挥功能，是决定正常和病理发育过程中细胞命运的基因调控机制的一部分。多项研究表明，不同 PcG 蛋白的失调与肿瘤的进展有关。胰腺导管腺癌是一种侵袭性肿瘤，遵循多步骤的进展模型，通过称为胰腺上皮内瘤变（PanIN）的前体病变。本研究的目的是研究 PcG 蛋白 CBX7 在胰腺发生中的作用，并评估其可能的诊断和预后意义。我们通过免疫组织化学分析了 210 例来自切除标本的导管性胰腺腺癌中 CBX7 的表达，这些标本组合在组织微阵列（TMA）上，包括另外 40 例 PanIN 病例和 40 例正常对照。使用接收者操作特征（ROC）曲线分析来选择截止评分，并将结果与肿瘤的临床病理参数和患者的结局相关联。还评估了 CBX7 正调控的 E-钙黏蛋白的表达。在正常胰腺组织、PanIN 和侵袭性导管腺癌之间发现 CBX7 蛋白表达存在显著差异，且呈逐渐下降趋势。CBX7 表达缺失与胰腺腺癌恶性程度增加相关，而 CBX7 表达的维持则显示出生存时间延长的趋势。此外，E-钙黏蛋白表达缺失与 CBX7 缺失相关，并与患者生存预后不良相关。这些结果表明，CBX7 在胰腺发生中起作用，其表达缺失与侵袭性表型相关。
