Detection of high-risk intraductal papillary mucinous neoplasm and pancreatic adenocarcinoma

Abstract

The present invention relates to diagnostic, prognostic and clinical methods of distinguishing high-risk IPMN from more benign IPMN as well as high-grade PanIN and PDAC from low-grade PanIN with moderate sensitivity and very high specificity using Das-1 and related antibodies.

What is claimed is: 
     
         1 . A method for determining whether a subject has, or is at risk of having, high-risk intraductal papillary mucinous neoplasm (IPMN), high grade pancreatic intraepithelial neoplasia (PanIN), or pancreatic ductal adenocarcinoma (PDAC), comprising
 contacting a pancreatic tissue sample from a subject suspected of having high-risk IPMN, high grade PanIN, or PDAC with a Das 1 antibody or an antigen binding portion thereof;   detecting immunoreactivity between the pancreatic tissue and the antibody, the presence of the immunoreactivity indicating a positive diagnosis of high-risk IPMN, high grade PanIN, or PDAC, and   identifying the sample or the subject as having, or being at risk of having, high-risk IPMN, high grade PanIN, or PDAC if there is immunoreactivity between the pancreatic tissue and the antibody.   
     
     
         2 . The method of  claim 1 , wherein the identifying step further comprises generating a report specifying that the pancreatic tissue sample or the subject has, or is at risk of having, high-risk IPMN, high grade PanIN, or PDAC. 
     
     
         3 . The method of  claim 1 , wherein the detecting step further comprises obtaining a level of the immunoreactivity, and comparing the level to a predetermined level. 
     
     
         4 . The method of  claim 1 , wherein the detecting step is performed by immunoblot, immunohistochemistry, immunocytochemistry, immunoperoxidase staining, immunofluorescence, immunoelectronmicroscopy, or ELISA. 
     
     
         5 . The method of  claim 4 , wherein the detecting step is performed by immunoperoxidase staining. 
     
     
         6 . The method of  claim 1 , further comprising performing a negative control assay on a negative control sample to detect a Das 1 antibody-binding antigen in the negative control sample. 
     
     
         7 . The method of  claim 1 , further comprising performing a positive control assay on a positive control sample to detect a Das 1 antibody-binding antigen in the positive control sample. 
     
     
         8 . The method of  claim 1 , wherein method further comprises, before the contacting step, obtaining the pancreatic tissue sample from the subject. 
     
     
         9 . The method of  claim 1 , further comprising conducting a histology examination of the tissue sample. 
     
     
         10 . The method of  claim 1 , wherein the antibody is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a multispecific antibody, an antibody fragment, a recombinant antibody, and a chemically modified antibody. 
     
     
         11 . The method of  claim 1 , wherein the antibody or portion thereof is directly or indirectly attached to a detectable label. 
     
     
         12 . The method of  claim 11 , wherein the antibody fragment is Fab, F(ab′) 2 , scFv, Fv, Fab/c, a digestion product of an antibody using a proteolytic enzyme, or an antibody prepared using a recombinant DNA technique. 
     
     
         13 . The method of  claim 10 , wherein the antibody is a monoclonal antibody. 
     
     
         14 . The method of  claim 1 , wherein the sample is a surgically or endoscopically resected pancreatic tissue sample. 
     
     
         15 . The method of  claim 14 , wherein the sample comprises pancreatic tissue, pancreatic tumor, pancreatic cells, pancreatic cyst fluid, or pancreatic juice. 
     
     
         16 . The method of  claim 1 , wherein the sample is a body fluid sample. 
     
     
         17 . The method of  claim 16 , where in the sample is selected from the group consisting of blood, serum, plasma, pancreatic cyst fluid, and pancreatic juice. 
     
     
         18 . A method for diagnosing or grading intraductal papillary mucinous neoplasm (IPMN), pancreatic intraepithelial neoplasia (PanIN), or pancreatic ductal adenocarcinoma (PDAC), comprising:
 contacting a pancreatic tissue sample from a subject suspected of having IPMN, PanIN, or PDAC with a Das-1 antibody or an antigen binding portion thereof;   detecting immunoreactivity between the pancreatic tissue and the antibody to obtain a level of the immunoreactivity;   comparing the level of the immunoreactivity with a predetermined level; and   classifying the subject with an elevated level of the immunoreactivity as having IPMN, PanIN, or PDAC.   
     
     
         19 . The method of  claim 18 , wherein the level of the immunoreactivity is a number or percentage of cells positive for the immunoreactivity, or the level of the immunoreactivity is an expression level of the Das-1 antibody-1-binding antigen. 
     
     
         20 . A method for determining the malignant potential of a pancreatic cyst comprising:
 contacting a pancreatic cyst fluid sample from a pancreatic cyst of a subject with a Das-1 antibody or an antigen binding portion thereof;   detecting immunoreactivity between the sample and the antibody, the presence of the immunoreactivity indicating that the pancreatic cyst is malignant;   identifying the pancreatic cyst or the subject as having, or being at risk of having, malignant pancreatic cyst if there is immunoreactivity between the pancreatic tissue and the antibody.   
     
     
         21 . A method of assessing pancreatic cancer prognosis in a subject, comprising
 contacting a pancreatic tissue sample from a subject with a Das-1 antibody or an antigen binding portion thereof;   detecting immunoreactivity between the pancreatic tissue and the antibody to obtain a level of the immunoreactivity;   comparing the level of the immunoreactivity with a predetermined level; and   classifying the subject as having a good prognosis if the level of the immunoreactivity decreases after receiving a treatment or as having a poor prognosis if the level of the immunoreactivity level fails to increase after receiving the treatment.   
     
     
         22 . The method of  claim 21 , wherein the classifying step further comprises generating a report specifying that the subject has a good prognosis or a poor prognosis. 
     
     
         23 . The method of  claim 21 , wherein the predetermined level is obtained from the subject at a different point of time during his or her treatment. 
     
     
         24 . The method of  claim 23 , wherein the predetermined level is obtained from the subject prior to receiving the treatment.