Local recurrence in mismatch repair-proficient colon cancer predicted by an infiltrative tumor border and lack of CD8+ tumor-infiltrating lymphocytes
Local recurrence in mismatch repair-proficient colon cancer predicted by an infiltrative tumor border and lack of CD8+ tumor-infiltrating lymphocytes
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DOI：
10.1158/1078-0432.ccr-08-0048
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发表时间：
2008-06-15
影响因子：
11.5
通讯作者：
Lugli, Alessandro
中科院分区：
文献类型：
--
作者：
Zlobec, Inti;Terracciano, Luigi M.;Lugli, Alessandro
目的：识别局部复发高风险的结肠癌患者是必要的，以改善患者的选择，更有针对性的治疗方案。本研究的目的是开发一个预测模型，通过评估7个临床病理特征，24个蛋白质标记物的肿瘤进展的独立预测效果，和他们的多功能组合在错配修复熟练的结肠cancer.Experimental Design：269例患者的完整的临床病理数据的24个蛋白质标记物的免疫组化。经过单变量和多变量分析，确定了局部复发的独立预测因子，并分析了其多特征组合。结果：119例（55.8%）患者术后局部复发，其中11例（55.8%）患者术后复发率明显高于其他患者（P <0.05）。肿瘤复发的独立预测因子是淋巴结转移（P = 0.006）、无CD 8（+）肿瘤浸润淋巴细胞（TIL; P < 0.001）和浸润性肿瘤边缘（P < 0.001）。在调整辅助治疗后，这种独立效应持续存在。具有这三种不良特征的患者的复发风险为0.75，5年生存率为8.8%。淋巴结阴性、肿瘤边缘浸润、无CD 8（+）TIL的患者被确定为高风险，复发概率为0.55，5年生存率为60%。其余淋巴结阴性病例的风险为8%~ 26%，5年生存率为97.6%。结论：浸润性肿瘤边缘和CD 8（+）TIL缺失是淋巴结阴性错配修复活跃的结肠癌局部复发的高度预测因素，有助于识别可能受益于辅助化疗的高危患者。
Purpose: The identification of colon cancer patients at high risk of local recurrence is necessary to improve the selection of patients for more tailored treatment protocols. The aim of this study was to develop a predictive model of local recurrence by assessing the independent predictive effect of 7 clinicopathologic features, 24 protein markers of tumor progression, and their multifeature combinations in mismatch repair-proficient colon cancers.Experimental Design: Immunohistochemistry for 24 protein markers was done on 269 patients with complete clinicopathologic data. After univariate and multivariable analyses, independent predictors of local recurrence were identified and their multifeature combinations were analyzed. Kaplan-Meier and Cox proportional hazards regression were done for survival analysis.Results: Local recurrence was observed in 119 patients (55.8%). Independent predictors of tumor recurrence were lymph node involvement (P = 0.006), absence of CD8(+) tumor-infiltrating lymphocytes (TIL; P < 0.001), and infiltrative tumor margin (P < 0.001). This independent effect persisted after adjusting for adjuvant therapy. Risk of recurrence was 0.75 and the 5-year survival rate was 8.8% in patients with these three adverse features. Node-negative patients with an infiltrative tumor margin and absence of CD8(+) TILs were identified as high risk with a probability of 0.55 for recurrence and a 60% 5-year survival rate. The remaining node-negative cases fared significantly better with risks ranging from 8% to 26% and 5-year survival rates reaching 97.6%.Conclusions: An infiltrative tumor margin and absence of CD8(+) TILs are highly predictive of local recurrence in node-negative mismatch repair-proficient colon cancer and may help to identify high-risk patients who may benefit from adjuvant chemotherapy.