MUC4/16 assay for the early diagnosis and management of benign and malignant pancreatic diseases

Abstract The goal of this Fast track application is to develop a non invasive diagnostic testbased on MUCand MUCmucinsthat can serve as an adjunct to cytological analysis of fine needle aspiratesFNAsfor accurate prediction of malignancy in patients with cystic pancreatic lesionsDue to asymptomatic nature and lack of methods for early detectionandgtof pancreatic cancerPCpatients present with an unresectable primary tumor with distant metastasis at the time of diagnosisWhile the overallyear survival rate of pancreatic cancer is dismalsigni cantly better outcomes have been reported for smaller tumors detected at an earlier stageSlow development of PC in conjunction with the better curative response of patients with early disease underscore the need of early detection of pancreatic cancerPancreatic cystic lesionsearlier considered to be rareare increasingly being recognized due to increased number of individuals being subjected to diagnostic imaginghowevertheir exact prevalence is unknownThese cystic pancreatic lesions have variable malignant potentialwhile mucinous cystic neoplasmsMCNsand intraductal pancreatic mucinous neoplasmsIPMNshave a high probability of developing into malignant lesionsserous cystic neoplasmsSCNsare considered benignDespite the critical needaccurate discrimination between highand low risk cystic lesions is challenging due to their symptomatic and radiographic similaritiesAlthough cytologic examination of endoscopic ultrasoundEUSguided fine needle aspiratesFNAshas emerged as an indispensable part of presurgical evaluationin practiceof such analyses are inconclusive and unreliable in discriminating between serous and mucinous lesionsUsing anti MUCMAbGgenerated by our group several studies have established that cell surface mucin MUCis promising prognostic and diagnostic biomarkerFurther MUCand MUCexhibitedspecificity for malignancy in EUS FNAs containing atypical ductal epithelial cellsThe central hypothesis of this proposal Detection of MUCand or MUCin pancreatic tissuesEUS FNAsis positively correlated with the presence of already existing pancreatic cancer or cystic lesions with malignant potential and thus MUCstaining is a powerful tool for the accurate prediction of malignancy and pre surgical stratification of patients with cystic lesions of the pancreasStudies proposed for Phase I will result in the development of a prototype kit for MUC MUCIHCAimand provide proof of concept in support of the aforementioned hypothesisStudies proposed in Phase II will validate the significance of MUCimmunostaining in a blinded trial and determine how MUCexpression correlates with the clinical outcome of the solid cystic pancreatic diseasesAimFurtherwe propose to test the prototype kit in a clinical settingCLIA Labto validate performanceAimOverallthe proposal will lead to the development of a clinical test to stratify patients for surgical intervention or surveillance in the context of pancreatic cystic lesions and PC Project Narrative Endoscopic UltrasoundEUSbased Fine Needle AspiratesFNAsrepresent a valuable pre surgical diagnostic material for confirming the presence or risk malignant lesions in the pancreashowever their diagnostic utility is limited due to the poor sensitivity of cytological analysis particularly in cases exhibiting atypical epithelial cellsAccurate diagnosis of malignant lesions of the pancreas can provide opportunity for intervention at a curable stage and reduce the risk of surgery associate morbidity in patients harboring benign lesionsThe proposed studies will validate if MUCand MUCstaining in EUS FNAs can predict the risk of malignant lesions and help in appropriate patient selection for surgical resection