Koushik K Das1, Xin Geng2, Jeffrey W Brown3, Vicente Morales-Oyarvide4, Tiffany Huynh5, Ilaria Pergolini4, Martha B Pitman5, Cristina Ferrone4, Mohammad Al Efishat6, Dana Haviland6, Elizabeth Thompson7, Christopher Wolfgang8, Anne Marie Lennon9, Peter Allen6, Keith D Lillemoe4, Ryan C Fields10, William G Hawkins10, Jingxia Liu10, Carlos Fernandez-Del Castillo4, Kiron M Das2, Mari Mino-Kenudson11. 1. Division of Gastroenterology, Washington University, St Louis, Missouri. Electronic address: k.das@wustl.edu. 2. Division of Gastroenterology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey. 3. Division of Gastroenterology, Washington University, St Louis, Missouri. 4. Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts. 5. Deparment of Pathology, Massachusetts General Hospital, Boston, Massachusetts. 6. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. 7. Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland. 8. Department of Surgery Johns Hopkins School of Medicine, Baltimore, Maryland. 9. Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland. 10. Department of Surgery, Washington University, St Louis, Missouri. 11. Deparment of Pathology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: mminokenudson@partners.org.
Abstract
BACKGROUND & AIMS: Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort. METHODS: We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features. RESULTS: The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA <.001). When we controlled for Das-1 in multivariate regression, main pancreatic duct dilation >5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation ≥1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P = .0397) were significantly associated with high-risk PCLs. CONCLUSIONS: We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy.
BACKGROUND & AIMS: Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort. METHODS: We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features. RESULTS: The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA <.001). When we controlled for Das-1 in multivariate regression, main pancreatic duct dilation >5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation ≥1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P = .0397) were significantly associated with high-risk PCLs. CONCLUSIONS: We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy.
Authors: Koushik K Das; Jeffrey W Brown; Carlos Fernandez Del-Castillo; Tiffany Huynh; Jason C Mills; Yoko Matsuda; Kiron M Das; Mari Mino-Kenudson Journal: Hum Pathol Date: 2021-01-30 Impact factor: 3.466
Authors: Katherine S Yang; Debora Ciprani; Aileen O'Shea; Andrew S Liss; Robert Yang; Sarah Fletcher-Mercaldo; Mari Mino-Kenudson; Carlos Fernández-Del Castillo; Ralph Weissleder Journal: Gastroenterology Date: 2020-12-07 Impact factor: 22.682
Authors: Ying Liu; Sukhwinder Kaur; Ying Huang; Johannes F Fahrmann; Jo Ann Rinaudo; Samir M Hanash; Surinder K Batra; Aatur D Singhi; Randall E Brand; Anirban Maitra; Brian B Haab Journal: Cancer Epidemiol Biomarkers Prev Date: 2020-06-12 Impact factor: 4.254