Turner Natalie, Wong Hui-Li, Templeton Arnoud, Tripathy Sagarika, Whiti Rogers Te, Croxford Matthew, Jones Ian, Sinnathamby Mathuranthakan, Desai Jayesh, Tie Jeanne, Bae Susie, Christie Michael, Gibbs Peter, Tran Ben
Walter & Eliza Hall Institute of Medical Research, Melbourne, Australia.
Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Australia.
Int J Cancer. 2016 Feb 1;138(3):671-8. doi: 10.1002/ijc.29805. Epub 2015 Sep 2.
In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-to-lymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p = 0.001) and recurrence-free survival (HR 0.37, p = 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer.
在II期结肠癌中，多项独立研究表明，肿瘤内密集的免疫浸润（局部炎症）与预后改善相关，而通过各种标志物测量的全身炎症则与较差的预后相关。然而，以往的研究没有考虑局部和全身炎症之间的相互作用，也没有根据标准临床病理标准评估炎症反应的类型。为了评估炎症标志物在II期结肠癌中的潜在临床应用价值，我们对2000年至2010年间从一个前瞻性临床数据库中确定的一系列连续的II期结肠癌切除患者的局部和全身炎症进行了检查。通过病理学家对苏木精和伊红染色切片的复查评估，肿瘤内慢性炎症细胞（CIC）密度增加被用来代表局部炎症。根据术前全血细胞计数计算的中性粒细胞与淋巴细胞比值（NLR）>5被用来代表全身炎症。在确定的396例符合条件的患者中，局部和全身炎症之间存在非显著的负相关关系。CIC密度增加与总体生存率提高（风险比0.45，p = 0.001）和无复发生存率提高（风险比0.37，p = 0.003）显著相关。高NLR与较差的总体生存率显著相关（风险比2.56，p < 0.001）。这些标志物的组合进一步独立于标准高危标准对预后进行分层，占主导地位的全身炎症反应（低CIC/高NLR）与最差的预后相关（5年总体生存率55.8%）。经过进一步验证，这种简单、廉价的联合炎症生物标志物可能有助于II期结肠癌辅助化疗的患者选择。
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