Department of Gastroenterology & Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, the Netherlands.
Mod Pathol. 2020 Dec;33(12):2626-2636. doi: 10.1038/s41379-020-0598-9. Epub 2020 Jun 24.
Advanced colorectal cancer (CRC) consensus molecular subtype 4 (CMS4) or CRC with a low immunoscore is associated with shorter survival times. Non-metastatic CRC with microsatellite instability (MSI) is associated with a lower risk of recurrence. We evaluated outcome (lymph node metastases [LNM] or cancer recurrence) in these tumor subtypes in patients with surgically-removed non-pedunculated T1 CRC by performing a multicenter case-cohort study. We included all patients in 13 hospitals in the Netherlands from 2000-2014 (n = 651). We randomly selected a subgroup of patients (n = 223) and all patients with LNM or recurrence (n = 63), and median follow-up of 44 months. We centrally reviewed tumor-slides, and constructed and immunostained tissue microarrays determining MSI, CMS (MSI/CMS1, CMS2/3, or CMS4), and immunoscore (I-low/I-high). We used weighted Cox proportional hazard models to evaluate the association of MSI, CMS, and immunoscore with LNM or recurrence, adjusting for conventional histologic risk factors. In the randomly selected subgroup of patients, 7.1% of tumors were MSI/CMS1, 91.0% CMS2/3, 1.8% CMS4, and 25% I-low. In the case-cohort, patients with CMS4 tumors had an increased risk for LNM or recurrence compared with patients with tumors of other CMSs (adjusted hazard ratio [HR], 3.97; 95% CI, 1.12-14.06; P = 0.03). Albeit not significant, tumors with MSI had a lower risk for LNM or recurrence than other tumor subtypes (adjusted HR, 0.52; 95% CI, 0.12-2.30; P = 0.39), whereas tumors with a low immunoscore had an increased risk for LNM or recurrence (adjusted HR, 1.30; 95% CI, 0.68-2.48; P = 0.43). In conclusion, in a case-cohort study of patients with non-pedunculated T1 CRC, MSI, and immunoscore were not significantly associated with adverse outcome after surgery. CMS4 substantially increased the risk of adverse outcome. However, CMS4 is rare in T1 CRCs, limiting its value for determining the risk in patients.
晚期结直肠癌（CRC）共识分子亚型 4（CMS4）或免疫评分低的 CRC 与较短的生存时间相关。具有微卫星不稳定性（MSI）的非转移性 CRC 与较低的复发风险相关。我们通过进行多中心病例队列研究，评估了手术切除的无蒂 T1CRC 患者中这些肿瘤亚型的结局（淋巴结转移 [LNM] 或癌症复发）。我们纳入了 2000-2014 年荷兰 13 家医院的所有患者（n=651）。我们随机选择了一部分患者（n=223）和所有发生 LNM 或复发的患者（n=63），中位随访时间为 44 个月。我们对肿瘤切片进行了中心审查，并构建和免疫染色了组织微阵列，以确定 MSI、CMS（MSI/CMS1、CMS2/3 或 CMS4）和免疫评分（I-低/I-高）。我们使用加权 Cox 比例风险模型来评估 MSI、CMS 和免疫评分与 LNM 或复发的相关性，调整了常规组织学危险因素。在随机选择的患者亚组中，7.1%的肿瘤为 MSI/CMS1，91.0%为 CMS2/3，1.8%为 CMS4，25%为 I-低。在病例队列中，与其他 CMS 肿瘤患者相比，CMS4 肿瘤患者发生 LNM 或复发的风险增加（调整后的危险比 [HR]，3.97；95%CI，1.12-14.06；P=0.03）。尽管不显著，但 MSI 肿瘤的 LNM 或复发风险低于其他肿瘤亚型（调整后的 HR，0.52；95%CI，0.12-2.30；P=0.39），而低免疫评分的肿瘤 LNM 或复发风险增加（调整后的 HR，1.30；95%CI，0.68-2.48；P=0.43）。总之，在一项非蒂 T1CRC 患者的病例队列研究中，MSI 和免疫评分与手术后不良结局无显著相关性。CMS4 显著增加了不良结局的风险。然而，CMS4 在 T1CRC 中很少见，限制了其在确定患者风险方面的价值。
