OBJECTIVES: To evaluate the association of tumor-associated neutrophils (TANs) with malignant progression in intraductal papillary mucinous neoplasms (IPMNs) and to study the cyst fluid from these lesions for biomarkers of the inflammation-carcinogenesis association. BACKGROUND: There is a strong link between TANs and malignant progression. Inflammatory mediators released by these cells may be a measurable surrogate marker of this progression. METHODS: We evaluated 78 resected IPMNs (2004-2013). Lesions were divided into the low-risk (low- and intermediate-grade dysplasia: n = 48) and high-risk (high-grade dysplasia and invasive carcinoma: n = 30) groups. TANs were assessed and categorized (negative, low, and high). A multiplexed assay was performed to evaluate 87 different cyst fluid proteins, including cyst fluid inflammatory markers (CFIMs), as possible surrogate markers for parenchymal inflammation. RESULTS: Significant positive correlation between grade of dysplasia and TANs was found. High levels of TANs 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, of which 23 (79%) were CFIMs. Higher levels of TANs correlated with higher levels of 18 CFIMs, of which 16 (89%) were also found to be associated with higher grades of dysplasia. CONCLUSIONS: In this study, TANs were strongly associated with malignant progression in IPMNs. Measurement of CFIMs may be a surrogate marker for IPMN progression and allow for the identification of high-risk disease.
OBJECTIVES: To evaluate the association of tumor-associated neutrophils (TANs) with malignant progression in intraductal papillary mucinous neoplasms (IPMNs) and to study the cyst fluid from these lesions for biomarkers of the inflammation-carcinogenesis association. BACKGROUND: There is a strong link between TANs and malignant progression. Inflammatory mediators released by these cells may be a measurable surrogate marker of this progression. METHODS: We evaluated 78 resected IPMNs (2004-2013). Lesions were divided into the low-risk (low- and intermediate-grade dysplasia: n = 48) and high-risk (high-grade dysplasia and invasive carcinoma: n = 30) groups. TANs were assessed and categorized (negative, low, and high). A multiplexed assay was performed to evaluate 87 different cyst fluid proteins, including cyst fluid inflammatory markers (CFIMs), as possible surrogate markers for parenchymal inflammation. RESULTS: Significant positive correlation between grade of dysplasia and TANs was found. High levels of TANs 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, of which 23 (79%) were CFIMs. Higher levels of TANs correlated with higher levels of 18 CFIMs, of which 16 (89%) were also found to be associated with higher grades of dysplasia. CONCLUSIONS: In this study, TANs were strongly associated with malignant progression in IPMNs. Measurement of CFIMs may be a surrogate marker for IPMN progression and allow for the identification of high-risk disease.
Authors: Roberto Salvia; Carlos Fernández-del Castillo; Claudio Bassi; Sarah P Thayer; Massimo Falconi; William Mantovani; Paolo Pederzoli; Andrew L Warshaw Journal: Ann Surg Date: 2004-05 Impact factor: 12.969
Authors: Kristine S Spinelli; Travis E Fromwiller; Roger A Daniel; James M Kiely; Attila Nakeeb; Richard A Komorowski; Stuart D Wilson; Henry A Pitt Journal: Ann Surg Date: 2004-05 Impact factor: 12.969
Authors: Stefan Fritz; Carlos Fernandez-del Castillo; Mari Mino-Kenudson; Stefano Crippa; Vikram Deshpande; Gregory Y Lauwers; Andrew L Warshaw; Sarah P Thayer; A John Iafrate Journal: Ann Surg Date: 2009-03 Impact factor: 12.969
Authors: Tatsuo Hata; Marco Dal Molin; Seung-Mo Hong; Koji Tamura; Masaya Suenaga; Jun Yu; Hiraku Sedogawa; Matthew J Weiss; Christopher L Wolfgang; Anne Marie Lennon; Ralph H Hruban; Michael G Goggins Journal: Clin Cancer Res Date: 2017-02-01 Impact factor: 12.531
Authors: Mohammad A Al Efishat; Marc A Attiyeh; Anne A Eaton; Mithat Gönen; Denise Prosser; Anna E Lokshin; Carlos Fernández-Del Castillo; Keith D Lillemoe; Cristina R Ferrone; Ilaria Pergolini; Mari Mino-Kenudson; Neda Rezaee; Marco Dal Molin; Matthew J Weiss; John L Cameron; Ralph H Hruban; Michael I D'Angelica; T Peter Kingham; Ronald P DeMatteo; William R Jarnagin; Christopher L Wolfgang; Peter J Allen Journal: Ann Surg Date: 2018-08 Impact factor: 12.969
Authors: Jayasree Chakraborty; Abhishek Midya; Lior Gazit; Marc Attiyeh; Liana Langdon-Embry; Peter J Allen; Richard K G Do; Amber L Simpson Journal: Med Phys Date: 2018-09-27 Impact factor: 4.071
Authors: Kate A Harrington; Travis L Williams; Sharon A Lawrence; Jayasree Chakraborty; Mohammad A Al Efishat; Marc A Attiyeh; Gokce Askan; Yuting Chou; Alessandra Pulvirenti; Caitlin A McIntyre; Mithat Gonen; Olca Basturk; Vinod P Balachandran; T Peter Kingham; Michael I D'Angelica; William R Jarnagin; Jeffrey A Drebin; Richard K Do; Peter J Allen; Amber L Simpson Journal: J Med Imaging (Bellingham) Date: 2020-06-25
Authors: Mark Steven Miller; Peter Allen; Teresa A Brentnall; Michael Goggins; Ralph H Hruban; Gloria M Petersen; Chinthalapally V Rao; David C Whitcomb; Randall E Brand; Suresh T Chari; Alison P Klein; David M Lubman; Andrew D Rhim; Diane M Simeone; Brian M Wolpin; Asad Umar; Sudhir Srivastava; Vernon E Steele; Jo Ann S Rinaudo Journal: Pancreas Date: 2016-09 Impact factor: 3.327