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Pancreatic intraepithelial neoplasia (PanIN) is a microscopic precursor lesion to pancreatic ductal adenocarcinoma (PDAC); however, there are few biomarkers that segregate high-grade PanIN/PDAC from low-grade PanIN lesions. mAb Das-1 is a monoclonal antibody against a colonic epithelial antigen that is reactive to premalignant conditions of the upper gastrointestinal tract including Barrett's esophagus, incomplete-type gastric intestinal metaplasia, and intraductal papillary mucinous neoplasm of the pancreas at high risk of malignancy. We sought to examine a role for Das-1 expression in differentiating high-grade PanIN/PDAC from low-grade PanIN lesions. We examined surgical specimens from 86 patients and 2 autopsied pancreata (74 with and 14 without PDAC) with 107 distinct PanIN lesions, 74 PDAC cases, and 32 associated lymph node metastases, with internal controls of normal pancreatic ducts observed in 56 cases. All of the normal pancreatic duct controls (0/56) and low-grade PanIN (0/95) lesions were nonreactive to Das-1. Das-1 expression among high-grade PanIN (7/12, 58%), PDAC (55/74, 74%), and lymph node metastasis (21/32, 66%) cases was significantly higher (p < 0.0001). Clinicopathologically, Das-1 reactivity was significantly correlated with nodal metastasis (p = 0.021). Overall, the sensitivity, specificity, and accuracy of Das-1 in segregating high-grade PanIN/PDAC from low-grade PanIN lesions and normal ducts were 72%, 100%, and 90%, respectively. Thus, mAb Das-1 reacts with high specificity with high-grade PanIN and PDAC and may help in preoperative diagnosis and/or clinical risk stratification.

Titel:	mAb Das-1 identifies pancreatic ductal adenocarcinoma and high-grade pancreatic intraepithelial neoplasia with high accuracy.
Autor/in / Beteiligte Person:	Das, KK ; Brown, JW ; Fernandez Del-Castillo, C ; Huynh, T ; Mills, JC ; Matsuda, Y ; Das, KM ; Mino-Kenudson, M
Zeitschrift:	Human pathology, Jg. 111 (2021-05-01), S. 36-44
Veröffentlichung:	Philadelphia, PA : W B Saunders ; <i>Original Publication</i>: Philadelphia, W B. Saunders Co., 2021
Medientyp:	academicJournal
ISSN:	1532-8392 (electronic)
DOI:	10.1016/j.humpath.2021.01.003
Schlagwort:	Adenocarcinoma in Situ pathology Aged Antibodies metabolism Antibodies, Monoclonal Biomarkers, Tumor metabolism Carcinoma, Pancreatic Ductal pathology Female Humans Male Middle Aged Neoplasm Grading Pancreatic Neoplasms pathology Sensitivity and Specificity Adenocarcinoma in Situ diagnosis Antibodies analysis Biomarkers, Tumor analysis Carcinoma, Pancreatic Ductal diagnosis Pancreatic Neoplasms diagnosis
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Language: English [Hum Pathol] 2021 May; Vol. 111, pp. 36-44. <i>Date of Electronic Publication: </i>2021 Jan 30. MeSH Terms: Adenocarcinoma in Situ / diagnosis ; Antibodies / analysis ; Biomarkers, Tumor / analysis ; Carcinoma, Pancreatic Ductal / diagnosis ; Pancreatic Neoplasms / *diagnosis ; Adenocarcinoma in Situ / pathology ; Aged ; Antibodies / metabolism ; Antibodies, Monoclonal ; Biomarkers, Tumor / metabolism ; Carcinoma, Pancreatic Ductal / pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Pancreatic Neoplasms / pathology ; Sensitivity and Specificity References: Mod Pathol. 2003 Oct;16(10):996-1006. (PMID: 14559982) ; Gastroenterology. 2019 Sep;157(3):720-730.e2. (PMID: 31175863) ; Br J Surg. 2011 Aug;98(8):1041-55. (PMID: 21644238) ; Cancer Res. 2014 Jun 1;74(11):2913-21. (PMID: 24840647) ; Am J Gastroenterol. 2001 Aug;96(8):2480-5. (PMID: 11513194) ; Cell. 2012 Jan 20;148(1-2):349-61. (PMID: 22265420) ; Pancreas. 2005 Nov;31(4):344-9. (PMID: 16258368) ; Int J Cancer. 2012 May 15;130(10):2349-58. (PMID: 21732341) ; J Immunol. 1987 Jul 1;139(1):77-84. (PMID: 3295053) ; CA Cancer J Clin. 2011 Jul-Aug;61(4):212-36. (PMID: 21685461) ; Gut. 2003 Jun;52(6):807-12. (PMID: 12740335) ; Cancer. 1979 Apr;43(4):1418-28. (PMID: 445339) ; Am J Surg Pathol. 2001 May;25(5):579-86. (PMID: 11342768) ; Pathobiology. 2000 Mar-Apr;68(2):76-86. (PMID: 10878504) ; Mod Pathol. 2003 Sep;16(9):902-12. (PMID: 13679454) ; Am J Surg Pathol. 2004 Aug;28(8):977-87. (PMID: 15252303) ; Am J Pathol. 2000 Jun;156(6):2123-33. (PMID: 10854233) ; Am J Surg Pathol. 2005 Feb;29(2):188-95. (PMID: 15644775) ; Ann Intern Med. 1994 May 1;120(9):753-6. (PMID: 7511878) ; J Clin Invest. 2011 Dec;121(12):4572-8. (PMID: 22133881) ; Clin Gastroenterol Hepatol. 2010 Feb;8(2):206-12. (PMID: 19765677) ; Cancer. 2000 Jun 1;88(11):2495-504. (PMID: 10861425) ; Gut. 1993 May;34(5):650-7. (PMID: 8504966) ; Gut. 2014 Oct;63(10):1626-34. (PMID: 24277729) ; Am J Pathol. 2001 May;158(5):1677-83. (PMID: 11337365) ; Gastroenterology. 2012 Apr;142(4):730-733.e9. (PMID: 22226782) ; Mod Pathol. 2004 Jan;17(1):62-74. (PMID: 14631367) ; Am J Surg Pathol. 2015 Dec;39(12):1730-41. (PMID: 26559377) ; Pancreas. 2017 May/Jun;46(5):658-664. (PMID: 28196020) ; Cancer. 1999 Jan 15;85(2):326-32. (PMID: 10023699) ; Dig Dis Sci. 2000 Jan;45(1):40-8. (PMID: 10695612) ; Pancreatology. 2007;7(4):341-6. (PMID: 17703080) ; Clin Cancer Res. 2000 Aug;6(8):2969-72. (PMID: 10955772) ; Cancer Res. 2000 Apr 1;60(7):2002-6. (PMID: 10766191) Grant Information: P30 DK052574 United States DK NIDDK NIH HHS; R01 DK063618 United States DK NIDDK NIH HHS; T32 DK007130 United States DK NIDDK NIH HHS Contributed Indexing: Keywords: Biomarker; CEP; Pancreatic adenocarcinoma; Pancreatic intraepithelial neoplasia (PanIN); mAb Das-1 Substance Nomenclature: 0 (Antibodies) ; 0 (Antibodies, Monoclonal) ; 0 (Biomarkers, Tumor) ; 0 (DAS-1 protein, human) Entry Date(s): Date Created: 20210201 Date Completed: 20211015 Latest Revision: 20220503 Update Code: 20240513 PubMed Central ID: PMC8817765

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mAb Das-1 identifies pancreatic ductal adenocarcinoma and high-grade pancreatic intraepithelial neoplasia with high accuracy.