Methods for Diagnosing and Treating Kidney and Colorectal Cancer

Abstract

Methods, reagents and kits for diagnosing and treating cancer such as kidney or colorectal cancer are disclosed. An immunoassay for detecting kidney or colorectal cancer is based on the relative change of the ADAMTSL4 protein in urine or blood compared with normal tissue. An immunohistochemical assay for detecting kidney or colorectal cancer is based on the relative absence of labeled antibody binding to cancerous tissue, compared with normal tissue.

1 . An antibody which specifically binds an epitope contained within a sequence selected from the group consisting of an ADAMTSL4 isoform 1 amino acid sequence defined by SEQ ID NO:11 and an ADAMTSL4 isoform 2 amino acid sequence defined by SEQ ID NO:12. 
     
     
         2 . The antibody of  claim 1  which specifically binds an epitope contained within a sequence selected from the group consisting of amino acid residues 1009 to 1024 of human ADAMTSL4 isoform 1 defined by SEQ ID NO:1 and amino acid residues 693-710 of human ADAMTSL4 defined by SEQ ID NO:2. 
     
     
         3 . The antibody of  claim 1 , labeled with a detectable marker suitable for immunohistochemical detection of cancerous kidney, colorectal, or neuronal tissue, based on the relative absence of histochemical staining of the tissue compared with normal kidney, colorectal or neuronal issue, respectively. 
     
     
         4 . The antibody of  claim 1 , wherein the antibody is a polyclonal antibody. 
     
     
         5 . The antibody of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         6 . A diagnostic device for use in for screening for kidney or colorectal cancer in a subject, or staging treatment of kidney or colorectal cancer in a subject, comprising:
 (a) a structure for receiving a body-fluid sample from the subject,   (b) an antibody which specifically binds a selected domain or epitope of ADAMTSL4, wherein the antibody is associated with the structure and capable of reacting with the body-fluid received in the structure to produce, in combination with other reagents associated with the structure, a detectable reaction product indicative of the presence and/or level of ADAMTSL4 containing that epitope or domain, and   (c) a known standard indicator which, in combination with the reagents, produces a known standard reaction product indicative of kidney or colorectal cancer, against which the level of detectable body-fluid reaction product can be assessed.   
     
     
         7 . The device of  claim 6 , wherein said structure includes a porous pad having the antibody embedded therein, for reaction with the body-fluid sample when the sample is applied to the pad, and said detectable body-fluid reaction product is indicated by a colorimetric or fluorimetric indicator. 
     
     
         8 . The device of  claim 6 , which includes a spectrophotometric detector for generating a signal related to the level of reaction product, a microprocessor for comparing said signal with a signal value from the known standard indicator, and a display for displaying an output of the microprocessor. 
     
     
         9 . The device of  claim 6 , wherein the antibody specifically binds an epitope contained within SEQ ID NO:1 or SEQ ID NO:2. 
     
     
         10 . A method of screening for colorectal cancer in a human subject, or staging treatment of colorectal cancer in a subject, comprising:
 reacting a body-fluid sample from the subject with an antibody which specifically binds a selected domain or epitope of ADAMTSL4, and   determining, from the presence and/or amount of immunoassay product, whether the subject has a reduced level of antibody binding to the selected domain or epitope of ADAMTSL4, as compared to a normal range of antibody binding to the selected domain or epitope of ADAMTSL4 in human samples, wherein the reduced level of antibody binding to the selected domain or epitope of ADAMTSL4 indicates the presence of and/or staging treatment of colorectal cancer.   
     
     
         11 . The method of  claim 10 , wherein the body-fluid sample is urine, and the level of ADAMTSL4 indicative or colorectal cancer is less than about 0.1 ng/ml. 
     
     
         12 . The method of  claim 10 , wherein said reacting includes applying the body fluid to a solid-phase immunoassay device, the level of ADAMTSL4 in the sample is indicated qualitatively by a colorimetric or fluorometric indicator, and said determining includes comparing the indicator with a known standard.