Zafrakas Menelaos, Tarlatzis Basil C, Streichert Thomas, Pournaropoulos Fotios, Wölfle Ute, Smeets Serge J, Wittek Britta, Grimbizis Grigorios, Brakenhoff Ruud H, Pantel Klaus, Bontis John, Günes Cagatay
Heinrich-Pette-Institute for Experimental Virology and Immunology, University of Hamburg, 20251 Hamburg, Germany.
Int J Mol Med. 2008 Mar;21(3):335-44.
The aim of the present study was to investigate whether endometriosis and cancer share common molecular characteristics. Tissue samples were collected prospectively during diagnostic laparoscopy of patients with primary infertility. Using high-density oligonucleotide microarrays, (Affymetrix Gene Chip HG-U133 Set) the genome-wide gene expression profile of advanced ovarian endometriosis was analyzed compared with matched normal endometrium. Expression of TERT, the gene encoding the telomerase reverse transcriptase subunit, and telomerase activity were analyzed in eutopic and ectopic endometrium. Genome-wide, high-resolution array-CGH was used to screen for genomic aberrations in endometriosis. Expression microarray data were validated quantitatively with RT-PCR. The genes RARRES1 and RARRES2 (retinoic acid receptor responder 1 and 2) were found to be up-regulated in endometriosis, suggesting a high degree of differentiation. Consistently, down-regulated genes included those involved in the cell cycle, cell metabolism and homeostasis. Expression of TERT and telomerase activity were present in eutopic but absent in ectopic endometrium. Array-CGH revealed a normal genomic pattern without gross amplifications and deletions. In conclusion, these data suggest that advanced ovarian endometriosis represents a highly differentiated tissue with minimal or no malignant potential.
本研究的目的是调查子宫内膜异位症和癌症是否具有共同的分子特征。在对原发性不孕症患者进行诊断性腹腔镜检查期间前瞻性地收集组织样本。使用高密度寡核苷酸微阵列（Affymetrix基因芯片HG-U133 Set），将晚期卵巢子宫内膜异位症的全基因组基因表达谱与匹配的正常子宫内膜进行比较分析。分析了端粒酶逆转录酶亚基编码基因TERT的表达以及在位内膜和异位内膜中的端粒酶活性。使用全基因组、高分辨率阵列比较基因组杂交技术（array-CGH）筛选子宫内膜异位症中的基因组畸变。表达微阵列数据通过逆转录聚合酶链反应（RT-PCR）进行定量验证。发现视黄酸受体反应蛋白1和视黄酸受体反应蛋白2（RARRES1和RARRES2）基因在子宫内膜异位症中上调，表明分化程度较高。一致地，下调的基因包括那些参与细胞周期、细胞代谢和内环境稳定的基因。TERT的表达和端粒酶活性在位内膜中存在但在异位内膜中不存在。阵列比较基因组杂交技术显示基因组模式正常，无明显扩增和缺失。总之，这些数据表明晚期卵巢子宫内膜异位症代表一种高度分化的组织，具有最小或无恶性潜能。
