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American Journal of Surgery

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Circulating Thrombospondin-2 enhances prediction of malignant intraductal papillary mucinous neoplasm - 17/02/19

Doi : 10.1016/j.amjsurg.2018.08.026 
Rachel E. Simpson a, g, Michele T. Yip-Schneider a, e, f, g, Huangbing Wu a, g, Hao Fan i, Ziyue Liu c, Murray Korc b, d, f, h, Jianjun Zhang f, i, ⁎ , C. Max Schmidt a, b, e, f, g, ⁎
a Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA 
b Department of Biochemistry/Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA 
c Department of Biostatistics, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA 
d Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA 
e Walther Oncology Center, Indianapolis, IN, USA 
f Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA 
g Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indiana University School of Medicine, Indianapolis, IN, USA 
h The Pancreatic Cancer Signature Center at IUPUI, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA 
i Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA 

∗Corresponding author. Departments of Surgery, Biochemistry & Molecular Biology, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 129, Indianapolis, IN, 46202, USA.Departments of Surgery, Biochemistry & Molecular BiologyIndiana University School of Medicine545 Barnhill DriveEmerson Hall 129IndianapolisIN46202USA∗∗Corresponding author. Department of Epidemiology, Indiana University Fairbanks School of Public Health, 1050 Wishard Blvd. RG5118, Indianapolis, IN, 46202, USA.Department of EpidemiologyIndiana University Fairbanks School of Public Health1050 Wishard Blvd. RG5118IndianapolisIN46202USA

Abstract

Background

IPMNs are cystic pancreatic lesions with variable malignant potential. Thrombospondin-2 (THBS2)—an endogenous, anti-angiogenic matrix glycoprotein—may modulate tumor progression. We hypothesized that circulating levels of THBS2 could aid in preoperative prediction of malignant IPMN.

Methods

Preoperative serum/plasma samples were procured from patients undergoing surgery. Circulating levels of THBS2 were measured (enzyme-linked immunosorbent assay) and compared to surgical pathology IPMN dysplastic grade.

Results

164 patients underwent THBS2 testing (100 Low/Moderate-IPMN; 64 High-Grade/Invasive-IPMN). Circulating THBS2 (mean ± SD) was greater in High-Grade/Invasive-IPMN than Low/Moderate-grade IPMN (26.6 ± 12.7 ng/mL vs. 20.4 ± 8.2 ng/mL; P < 0.001). THBS2 (AUC = 0.65) out-performed CA19-9 (n = 144; AUC = 0.59) in predicting IPMN grade. The combination of THBS2, CA19-9, radiographic main-duct involvement, main-duct diameter, age, sex, and BMI (AUC 0.82; n = 137) provided a good prediction model for IPMN grade.

Conclusion

Circulating THBS2 is correlated with IPMN dysplasia grade. THBS2 alone did not strongly predict IPMN grade but rather strengthened prediction models for High-Grade/Invasive IPMN when combined with other clinical/biomarker data.

Il testo completo di questo articolo è disponibile in PDF.

Highlights

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Optimal management of IPMN relies on the ability to determine high-risk lesions (i.e. harbor HGD or Invasive disease).
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THBS2 alone modestly predicted IPMN dysplasia grade and enhanced predictive models when combined with clinical features.
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THBS2 may assist in recommending surgery for high-risk disease while avoiding unnecessary resection of low-risk lesions.

Il testo completo di questo articolo è disponibile in PDF.

Keywords : Pancreatic cyst, Intraductal papillary mucinous neoplasm, IPMN, Pancreatic cancer, Thrombospondin-2, Biomarker

Abbreviations : Intraductal papillary mucinous neoplasm, High Grade Dysplasia, Thrombospondin-2, Body mass index, Area under the curve, Pancreatic Ductal Adenocarcinoma, Pancreatic Stellate Cell


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Vol 217 - N° 3

P. 425-428 - marzo 2019 Ritorno al numero
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