Wirta Erkki-Ville, Seppälä Toni, Friman Marjukka, Väyrynen Juha, Ahtiainen Maarit, Kautiainen Hannu, Kuopio Teijo, Kellokumpu Ilmo, Mecklin Jukka-Pekka, Böhm Jan
Department of SurgeryCentral Finland Central HospitalJyväskyläFinland.
Department of SurgeryHelsinki University Central HospitalHelsinkiFinland.
J Pathol Clin Res. 2017 Jul 19;3(3):203-213. doi: 10.1002/cjp2.71. eCollection 2017 Jul.
The aim of this study was to investigate immune response and its prognostic significance in colon carcinomas using the previously described Immunoscore (IS). A population-based series of 779 colorectal cancers, operated on between 2000 and 2010, were classified according to tumour, node, metastasis (TNM) status, mismatch repair (MMR), and mutation status. Rectal cancer cases ( = 203) were excluded as a high proportion of these patients received preoperative neoadjuvant chemoradiotherapy. Tissue microarray (TMA) samples collected from the tumour centre and invasive front were immunostained for CD3 and CD8. Lymphocytes were then digitally calculated to categorize IS from grade 0 to 4. Samples adequate for IS were available from 510 tumours. IS was significantly associated with AJCC/UICC stage, T stage, lymph node and distant metastases, perineural and lymphovascular invasion, MMR status, and mutation status. For IS0, IS1, IS2, IS3 and IS4, respectively, the 5-year disease-free survival (DFS) rates were 59, 68, 78, 83 and 94% ( < 0.001); 5-year disease-specific survival (DSS) rates were 47, 55, 75, 80, and 89% ( < 0.001); and 5-year overall survival (OS) rates were 40, 44, 66, 61, and 76% ( < 0.001). IS was also prognostic for DFS, DSS, and OS within subsets of microsatellite-stable (MSS) and microsatellite-instable (MSI) disease. Multivariable analysis showed that IS, AJCC/UICC stage, lymphovascular invasion, and lymph node ratio in AJCC/UICC stage III disease were independent prognostic factors for DFS, DSS, and OS. Age was an independent prognostic factor for DSS and OS. Gender and mutation were independent prognostic factors for OS. In conclusion, IS differentiated patients with poor versus improved prognosis in MSS and MSI disease and across AJCC/UICC stages. IS, AJCC/UICC stage, lymphovascular invasion, and lymph node ratio in AJCC/UICC stage III disease were independent prognostic factors for DFS, DSS, and OS.
本研究旨在使用先前描述的免疫评分(IS)来研究结肠癌中的免疫反应及其预后意义。对2000年至2010年间接受手术的779例基于人群的结直肠癌系列病例,根据肿瘤、淋巴结、转移(TNM)状态、错配修复(MMR)和基因突变状态进行分类。直肠癌病例(n = 203)被排除,因为这些患者中有很大比例接受了术前新辅助放化疗。从肿瘤中心和浸润前沿收集的组织微阵列(TMA)样本进行CD3和CD8免疫染色。然后对淋巴细胞进行数字化计算,将IS分为0至4级。510个肿瘤有适合进行IS评估的样本。IS与美国癌症联合委员会/国际抗癌联盟(AJCC/UICC)分期、T分期、淋巴结和远处转移、神经周围和淋巴管浸润、MMR状态以及基因突变状态显著相关。对于IS0、IS1、IS2、IS3和IS4,5年无病生存率(DFS)分别为59%、68%、78%、83%和94%(P < 0.001);5年疾病特异性生存率(DSS)分别为47%、55%、75%、80%和89%(P < 0.001);5年总生存率(OS)分别为40%、44%、66%、61%和76%(P < 0.001)。在微卫星稳定(MSS)和微卫星不稳定(MSI)疾病亚组中,IS对DFS、DSS和OS也具有预后价值。多变量分析显示,IS、AJCC/UICC分期、淋巴管浸润以及AJCC/UICC III期疾病中的淋巴结比率是DFS、DSS和OS的独立预后因素。年龄是DSS和OS的独立预后因素。性别和基因突变是OS的独立预后因素。总之,IS在MSS和MSI疾病以及不同AJCC/UICC分期中区分了预后不良与预后改善的患者。IS、AJCC/UICC分期、淋巴管浸润以及AJCC/UICC III期疾病中的淋巴结比率是DFS、DSS和OS的独立预后因素。