Department of Medical Oncology, Medical Faculty, Istanbul Medipol University, TEM Avrupa Otoyolu Goztepe, Cikisi, No:1, Bagcilar, 34214, Istanbul, Turkey.
Department of Medical Oncology, Okmeydani Training and Research Hospital, Kaptan Paşa Mahallesi, Darülaceze Cad. No:25, 34384, Okmeydani, Istanbul, Turkey.
J Gastrointest Cancer. 2024 Mar;55(1):227-236. doi: 10.1007/s12029-023-00953-0. Epub 2023 Jun 22.
Colorectal cancer is common worldwide, and adjuvant treatment's benefit is still controversial. We designed this study to determine the role of MSI and CDX-2 status determined by immunohistochemistry (IHC) combined with the inflammatory markers and pathological parameters in predicting disease recurrence in stage II and III colon cancer.
A total of 226 stage II/III colon cancer patients with a median age of 59 years who underwent initial surgery were included in this retrospective study. The pathologic assessment of MSI and CDX-2 was performed twice by immunohistochemistry (IHC) and two different pathologists. No staining/weak staining below 10% of the tumor was accepted as CDX-2 negative, and any MSI clones with weak staining below 10% were accepted as MSI-H. The laboratory parameters were noted at the initial diagnosis.
One hundred twenty-one and 105 patients were diagnosed with stage III and II colon cancer. 58.0% of patients were male, 46 (20.4%) of tumor tissue were MSS, and 17 (7.5%) were CDX-2 negative. One hundred twenty-nine tumors were localized in the right colon. Disease recurrence was significantly correlated with tumor localization, CDX-2 status, stage at diagnosis, and preoperatively median CRP and CEA levels. DFS rates for MSS patients with CDX-2 negative and positive were 36.7% and 98.1%, respectively [p < 0.001]. There was no significant correlation between MSI status and CDX-2 status. MSI status, the presence of adjuvant treatment, and systemic inflammatory markers were not significant prognostic factors for DFS. CDX-2 status [HR:0.08, CI 95% 0.03-0.17, p < 0.001 HR: 1.7, CI 95% 1.1-3.0, p = 0.03], disease stage [HR:2.6, CI 95% 1.43-4.74], and preoperatively CEA levels [HR:4.1 CI 95% 2.18-785, p < 0.001 were independent significant prognostic factors for DFS.
CDX-2 loss was an independent prognostic factor for DFS and disease recurrence in early-stage colon cancer. MSS patients with CDX-2 loss had significantly worse survival outcomes, and this might be the reason for deciding on adjuvant chemotherapy.
结直肠癌在全球范围内较为常见，辅助治疗的获益仍存在争议。我们设计本研究旨在确定由免疫组织化学（IHC）确定的微卫星不稳定性（MSI）和 CDX-2 状态与炎症标志物和病理参数相结合，在预测 II 期和 III 期结肠癌疾病复发中的作用。
本回顾性研究共纳入 226 例中位年龄 59 岁的 II/III 期结肠癌患者，这些患者接受了初始手术。通过免疫组织化学（IHC）和两名不同的病理学家对 MSI 和 CDX-2 的病理评估进行了两次。肿瘤中低于 10%的无染色/弱染色被接受为 CDX-2 阴性，任何低于 10%的 MSI 克隆弱染色被接受为 MSI-H。在初始诊断时记录实验室参数。
121 例和 105 例患者被诊断为 III 期和 II 期结肠癌。58.0%的患者为男性，46 例（20.4%）肿瘤组织为 MSS，17 例（7.5%）为 CDX-2 阴性。129 例肿瘤位于右结肠。疾病复发与肿瘤定位、CDX-2 状态、诊断时的分期以及术前中位 CRP 和 CEA 水平显著相关。MSS 患者 CDX-2 阴性和阳性的 DFS 率分别为 36.7%和 98.1%（p<0.001）。MSI 状态与 CDX-2 状态之间无显著相关性。MSI 状态、辅助治疗的存在和全身炎症标志物均不是 DFS 的显著预后因素。CDX-2 状态[HR：0.08，95%CI 0.03-0.17，p<0.001；HR：1.7，95%CI 0.11-3.0，p=0.03]、疾病分期[HR：2.6，95%CI 1.43-4.74]和术前 CEA 水平[HR：4.1，95%CI 2.18-785，p<0.001]是 DFS 的独立显著预后因素。
CDX-2 缺失是早期结肠癌患者 DFS 和疾病复发的独立预后因素。MSS 患者 CDX-2 缺失的生存结局明显较差，这可能是决定辅助化疗的原因。
