Li Pan, Xiao Zhitao, Braciak Todd A, Ou Qingjian, Chen Gong, Oduncu Fuat S
Department of Hematology and Oncology, Medizinische Klinik und Poliklinik IV, Ludwig Maximilians University, Munich, Germany.
Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
PLoS One. 2017 Aug 2;12(8):e0181615. doi: 10.1371/journal.pone.0181615. eCollection 2017.
We performed a systematic screening of colorectal cancer (CRC) tissues to investigate whether mismatch repair (MMR) status and ERCC1 protein expression could be predictive of clinical outcomes for these patients following the recommendation of The Evaluation of Genomic Applications in Practice of Prevention (EGAPP).
The expression of four MMR genes and ERCC1 were assessed by immunohistochemistry (IHC) from cancer tissue samples of 2233 consecutive CRC patients.
We observed that most CRC patients with a proficient MMR (pMMR) status tended to have simultaneous ERCC1 protein expression (P< 0.001). Stage III CRC patients with deficient MMR (dMMR) had higher prognoses than the same stage patients with pMMR (DFS: 74% vs 65%, P = 0.04; OS: 79% vs 69%, P = 0.04). Here, dMMR is also associated with poorer survival for stage II patients after chemotherapy (DFS: 66% vs 78%, P = 0.04). Stage II and III patients that were shown to express ERCC1 protein had higher DFS and OS than those that were deficient in expression (stage II, DFS: 83% vs 70%, P = 0.006; OS 85% vs 73%, P = 0.02. Stage III, DFS: 67% vs56%, P = 0.03; OS: 71% vs 57%, P = 0.04).
Our results indicate that dMMR appeared to predictive of a survival benefit for stage III CRC patients. We also found the determination of ERCC1 expression to be useful for predicting DFS or OS for stage II and III CRC patients. In addition, the expression of MMR genes and ERCC1 showed a significant relationship.
我们按照《基因组应用于实践预防评估》(EGAPP)的建议,对结直肠癌(CRC)组织进行了系统筛查,以研究错配修复(MMR)状态和ERCC1蛋白表达是否可预测这些患者的临床结局。
通过免疫组织化学(IHC)对2233例连续CRC患者的癌组织样本评估4种MMR基因和ERCC1的表达。
我们观察到,大多数错配修复功能正常(pMMR)的CRC患者往往同时有ERCC1蛋白表达(P<0.001)。错配修复缺陷(dMMR)的III期CRC患者的预后高于相同分期的pMMR患者(无病生存期:74%对65%,P = 0.04;总生存期:79%对69%,P = 0.04)。此外,dMMR也与II期患者化疗后的较差生存相关(无病生存期:66%对78%,P = 0.04)。显示表达ERCC1蛋白的II期和III期患者的无病生存期和总生存期高于表达缺陷的患者(II期,无病生存期:83%对70%,P = 0.006;总生存期85%对73%,P = 0.02。III期,无病生存期:67%对56%,P = 0.03;总生存期:71%对5�%,P = 0.04)。
我们的结果表明,dMMR似乎可预测III期CRC患者的生存获益。我们还发现,测定ERCC1表达对预测II期和III期CRC患者的无病生存期或总生存期有用。此外,MMR基因和ERCC1的表达显示出显著关系。