Azzoni Cinzia, Bottarelli Lorena, Cecchini Stefano, Ziccarelli Antonio, Campanini Nicoletta, Bordi Cesare, Sarli Leopoldo, Silini Enrico Maria
Center for Molecular and Translational Oncology (COMT), Department of Biomedical, Biotechnological and Translational Sciences, Unit of Pathological Anatomy, University Hospital of Parma, Parma, Italy.
Center for Molecular and Translational Oncology (COMT), Department of Biomedical, Biotechnological and Translational Sciences, Unit of Pathological Anatomy, University Hospital of Parma, Parma, Italy.
Pathol Res Pract. 2014 Feb;210(2):111-7. doi: 10.1016/j.prp.2013.11.004. Epub 2013 Nov 22.
Topoisomerase I (Topo I) and thymidylate synthase (TS) are essential enzymes for the replication, transcription and repair of DNA, and are potential biomarkers in colorectal cancer (CRC). The aim of the study was to correlate the tissue expression of Topo I and TS in sporadic CRCs with relevant pathological and molecular features and patients' outcome. Topo I and TS expression was assessed by immunostaining in 112 consecutive primary CRCs. Increased expression of Topo I was found in 36% of tumors, preferentially rectal (50%) and with not otherwise specified (NOS) histology (44%). Topo I expression was associated with 18q allelic loss (LOH), (p=0.013), microsatellite stable phenotype (p=0.002) and normal expression of mismatch proteins hMLH1 and hMSH2 (p=0.0012 and p=0.02, respectively). High TS expression was found in 60% of tumors, more frequently in distal sites (62%) and with NOS histology (66%); no association with microsatellite instability was observed. Topo I seems to be involved in the chromosomal instability pathway of sporadic CRCs. Conversely, high TS expression is unlikely to affect the clinical behavior of microsatellite unstable CRCs.
拓扑异构酶I（Topo I）和胸苷酸合成酶（TS）是DNA复制、转录和修复所必需的酶，并且是结直肠癌（CRC）中的潜在生物标志物。本研究的目的是将散发性结直肠癌中Topo I和TS的组织表达与相关病理和分子特征以及患者预后相关联。通过免疫染色评估了112例连续原发性结直肠癌中Topo I和TS的表达。在36%的肿瘤中发现Topo I表达增加，以直肠癌（50%）和未另行指定（NOS）组织学类型（44%）为主。Topo I表达与18q等位基因缺失（LOH）相关（p=0.013）、微卫星稳定表型（p=0.002）以及错配蛋白hMLH1和hMSH2的正常表达相关（分别为p=0.0012和p=0.02）。在60%的肿瘤中发现TS高表达，在远端部位更常见（62%）且为NOS组织学类型（66%）；未观察到与微卫星不稳定性的关联。Topo I似乎参与了散发性结直肠癌的染色体不稳定途径。相反，TS高表达不太可能影响微卫星不稳定结直肠癌的临床行为。
