Tumor-associated Neutrophils and Malignant Progression in Intraductal Papillary Mucinous Neoplasms: An Opportunity for Identification of High-risk Disease.
Tumor-associated Neutrophils and Malignant Progression in Intraductal Papillary Mucinous Neoplasms: An Opportunity for Identification of High-risk Disease.
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DOI：
10.1097/sla.0000000000001044
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发表时间：
2015-12
影响因子：
9
通讯作者：
Allen PJ
中科院分区：
文献类型：
--
作者：
Sadot E;Basturk O;Klimstra DS;Gönen M;Lokshin A;Do RK;D'Angelica MI;DeMatteo RP;Kingham TP;Jarnagin WR;Allen PJ
评价肿瘤相关中性粒细胞（TAN）与IPMN恶性进展的相关性，并研究这些病变的囊液中炎症-癌变相关生物标志物。TAN与恶性进展之间存在密切联系。这些细胞释放的炎症介质可能是这种进展的可测量的替代标记物。我们评估了78例切除的IPMN（2004-2013）。病变分为低风险（低和中级异型增生：n=48）和高风险（高级别异型增生和浸润性癌：n=30）组。对TAN进行评估和分类（阴性、低、高）。进行多重测定以评价87种不同的囊液蛋白，包括囊液炎性标志物（CCLs），作为实质炎症的可能替代标志物。不典型增生的分级与TAN之间存在显著的正相关性，当按照不典型增生的分级分为低/中度不典型增生、高度不典型增生和浸润性癌时，高TAN分别在2%、33%和89%的病变中被确定（p<0.001）。还发现较高级别的异型增生与29种测量的蛋白质呈正相关，其中23种（79%）是CCLs。较高水平的TAN与较高水平的18种CCLs相关，其中16种（89%）也与较高级别的异型增生相关。在这项研究中，TAN与IPMN的恶性进展密切相关。测量Cefalin可能是IPMN进展的替代标志物，并允许识别高风险疾病。
To evaluate the association of Tumor-associated neutrophils (TAN) with malignant progression in IPMN, and to study the cyst fluid from these lesions for biomarkers of the inflammation-carcinogenesis association. There is a strong link between TAN and malignant progression. Inflammatory mediators released by these cells may be a measurable surrogate marker of this progression. We evaluated 78 resected IPMN (2004–2013). Lesions were divided into low-risk (low and intermediate grade dysplasia: n=48) and high-risk (high-grade dysplasia and invasive carcinoma: n=30) groups. TAN were assessed and categorized (negative, low, high). A multiplexed assay was performed to evaluate 87 different cyst fluid proteins, including cyst fluid inflammatory markers (CFIM), as possible surrogate markers for parenchymal inflammation. Significant positive correlation between grade of dysplasia and TAN was found. High TAN were identified in 2%, 33%, and 89% of the lesions when stratified by grade of dysplasia into low/intermediate-grade dysplasia, high-grade dysplasia, and invasive carcinoma, respectively (p<0.001). Higher grades of dysplasia were also found to have positive correlation with 29 of the measured proteins, from which 23 (79%) were CFIM. Higher levels of TAN correlated with higher levels of 18 CFIM, from which 16 (89%) were also found to be associated with higher grades of dysplasia. In this study, TAN were strongly associated with malignant progression in IPMN. Measurement of CFIM may be a surrogate marker for IPMN progression and allow for identification of high-risk disease.