Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-risk Mucinous Pancreatic Cystic Lesions
Menée à partir de fluides kystiques pancréatiques provenant de 169 patients, cette étude évalue la sensibilité et la spécificité d'un test ELISA utilisant l'anticorps monoclonal Das-1 pour identifier des lésions pancréatiques mucineuses présentant un risque élevé de malignité
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 ELISA analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms (IPMNs), 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 IPMNs, 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 IPMNs 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 (AUC) values, and conducted multivariate logistic regression using clinical and pathology features.
Results : The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity and 99% specificity, and 95% accuracy, at a cut-off 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%, 51.5%, and 73.7% 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 [OR], 14.98; 95% CI, 2.63–108; P<.0012), main pancreatic duct dilation ≥1cm (OR, 47.9; 95% CI, 6.39–490; P<.0001), and jaundice (OR, 6.16; 95% CI, 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 cancer.
Gastroenterology , résumé, 2018