Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions

Koushik K. Das, Xin Geng, Jeffrey W. Brown, Vicente Morales-Oyarvide, Tiffany Huynh, Ilaria Pergolini, Martha B. Pitman, Cristina Ferrone, Mohammad Al Efishat, Dana Haviland, Elizabeth Thompson, Christopher Wolfgang, Anne Marie O'Broin-Lennon, Peter Allen, Keith D. Lillemoe, Ryan C. Fields, William G. Hawkins, Jingxia Liu, Carlos Fernandez del Castillo, Kiron M. DasMari Mino-Kenudson

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)720-730.e2
JournalGastroenterology
Volume157
Issue number3
DOIs
StatePublished - Sep 1 2019

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Monoclonal Antibodies
Cyst Fluid
Enzyme-Linked Immunosorbent Assay
Neoplasms
Sensitivity and Specificity
Odds Ratio
Guidelines
Confidence Intervals
Biomarkers
Neoplasm Antibodies
Clinical Pathology
Pancreatic Ducts
Jaundice
Tertiary Care Centers
Area Under Curve
Cysts
Dilatation
Histology
Logistic Models
Carcinoma

Keywords

  • Intraductal Papillary Mucinous Neoplasm (IPMN)
  • mAb Das-1
  • Mucinous Cystic Neoplasm (MCN)
  • Pancreatic Cancer

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Das, K. K., Geng, X., Brown, J. W., Morales-Oyarvide, V., Huynh, T., Pergolini, I., ... Mino-Kenudson, M. (2019). Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions. Gastroenterology, 157(3), 720-730.e2. https://doi.org/10.1053/j.gastro.2019.05.014

Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions. / Das, Koushik K.; Geng, Xin; Brown, Jeffrey W.; Morales-Oyarvide, Vicente; Huynh, Tiffany; Pergolini, Ilaria; Pitman, Martha B.; Ferrone, Cristina; Al Efishat, Mohammad; Haviland, Dana; Thompson, Elizabeth; Wolfgang, Christopher; O'Broin-Lennon, Anne Marie; Allen, Peter; Lillemoe, Keith D.; Fields, Ryan C.; Hawkins, William G.; Liu, Jingxia; Castillo, Carlos Fernandez del; Das, Kiron M.; Mino-Kenudson, Mari.

In: Gastroenterology, Vol. 157, No. 3, 01.09.2019, p. 720-730.e2.

Research output: Contribution to journalArticle

Das, KK, Geng, X, Brown, JW, Morales-Oyarvide, V, Huynh, T, Pergolini, I, Pitman, MB, Ferrone, C, Al Efishat, M, Haviland, D, Thompson, E, Wolfgang, C, O'Broin-Lennon, AM, Allen, P, Lillemoe, KD, Fields, RC, Hawkins, WG, Liu, J, Castillo, CFD, Das, KM & Mino-Kenudson, M 2019, 'Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions', Gastroenterology, vol. 157, no. 3, pp. 720-730.e2. https://doi.org/10.1053/j.gastro.2019.05.014
Das, Koushik K. ; Geng, Xin ; Brown, Jeffrey W. ; Morales-Oyarvide, Vicente ; Huynh, Tiffany ; Pergolini, Ilaria ; Pitman, Martha B. ; Ferrone, Cristina ; Al Efishat, Mohammad ; Haviland, Dana ; Thompson, Elizabeth ; Wolfgang, Christopher ; O'Broin-Lennon, Anne Marie ; Allen, Peter ; Lillemoe, Keith D. ; Fields, Ryan C. ; Hawkins, William G. ; Liu, Jingxia ; Castillo, Carlos Fernandez del ; Das, Kiron M. ; Mino-Kenudson, Mari. / Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions. In: Gastroenterology. 2019 ; Vol. 157, No. 3. pp. 720-730.e2.
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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.",
keywords = "Intraductal Papillary Mucinous Neoplasm (IPMN), mAb Das-1, Mucinous Cystic Neoplasm (MCN), Pancreatic Cancer",
author = "Das, {Koushik K.} and Xin Geng and Brown, {Jeffrey W.} and Vicente Morales-Oyarvide and Tiffany Huynh and Ilaria Pergolini and Pitman, {Martha B.} and Cristina Ferrone and {Al Efishat}, Mohammad and Dana Haviland and Elizabeth Thompson and Christopher Wolfgang and O'Broin-Lennon, {Anne Marie} and Peter Allen and Lillemoe, {Keith D.} and Fields, {Ryan C.} and Hawkins, {William G.} and Jingxia Liu and Castillo, {Carlos Fernandez del} and Das, {Kiron M.} and Mari Mino-Kenudson",
year = "2019",
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doi = "10.1053/j.gastro.2019.05.014",
language = "English (US)",
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pages = "720--730.e2",
journal = "Gastroenterology",
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TY - JOUR

T1 - Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions

AU - Das, Koushik K.

AU - Geng, Xin

AU - Brown, Jeffrey W.

AU - Morales-Oyarvide, Vicente

AU - Huynh, Tiffany

AU - Pergolini, Ilaria

AU - Pitman, Martha B.

AU - Ferrone, Cristina

AU - Al Efishat, Mohammad

AU - Haviland, Dana

AU - Thompson, Elizabeth

AU - Wolfgang, Christopher

AU - O'Broin-Lennon, Anne Marie

AU - Allen, Peter

AU - Lillemoe, Keith D.

AU - Fields, Ryan C.

AU - Hawkins, William G.

AU - Liu, Jingxia

AU - Castillo, Carlos Fernandez del

AU - Das, Kiron M.

AU - Mino-Kenudson, Mari

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

KW - Intraductal Papillary Mucinous Neoplasm (IPMN)

KW - mAb Das-1

KW - Mucinous Cystic Neoplasm (MCN)

KW - Pancreatic Cancer

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