Use of IMP3 as a Prognostic Marker for Cancer

Abstract

Provided herein are methods and compositions for the prognostic evaluation of a patient suspected of having, or having, cancer by assessing the expression of IMP3 in a biological sample of a patient. Methods can be used at the time of initial diagnosis of malignant tumors to identify a group of patients with a high potential to develop progression or metastasis later. Therefore, methods not only are able to provide very useful prognostic information for patients but also can help clinicians to select a candidate patient likely to benefit from early and aggressive cancer therapy. Methods and compositions for the treatment of cancer associated with expression of IMP3 are also provided.

1 . A method for determining the prognosis of a subject having a cervical carcinoma, comprising the steps of: (a) obtaining from the subject a primary tumor biopsy of the cervix; and (b) determining the presence or level of IMP3 in the primary tumor, wherein the presence of IMP3 in the primary tumor of the subject indicates that the prognosis of the subject is poor and an essentially undetectable level of IMP3 in the primary tumor of the subject indicates that the prognosis of the subject is good. 
     
     
         2 . The method of  claim 1 , wherein the subject has a cervical squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN). 
     
     
         3 . The method of  claim 1 , further comprising determining at least one other factor, the presence, absence or level of which reasonably correlates with the prediction of invasion from high grade squamous intraepithelial lesion. 
     
     
         4 . The method of  claim 3 , further comprising determining the stage of the primary tumor. 
     
     
         5 . The method of  claim 1 , wherein the level of IMP3 is compared to a control value, wherein the control value is the level of IMP3 in non-cancerous cells of the same origin as those of the primary tumor or the level of IMP3 in cells of a primary tumor of the same type as that in the subject from a subject having a good prognosis. 
     
     
         6 . The method of  claim 1 , wherein determining the presence or level of IMP3 comprises determining the presence or level of IMP3 protein. 
     
     
         7 . The method of  claim 6 , wherein determining the presence or level of IMP3 protein comprises immunohistochemical staining. 
     
     
         8 . The method of  claim 7 , comprising using a computerized image analyzer for quantitative analysis. 
     
     
         9 . The method of  claim 1 , wherein the primary tumor is removed from the subject. 
     
     
         10 . A kit comprising an agent for detecting the presence or level of IMP3 and a control IMP3 value. 
     
     
         11 . The kit of  claim 10 , wherein the agent for detecting the presence or level of IMP3 is an antibody or a fragment thereof. 
     
     
         12 . The kit of  claim 10 , further comprising at least one other agent for detecting the presence or level of a biomarker other than IMP3. 
     
     
         13 . A method for monitoring the progression of a cervical carcinoma in a subject, comprising detecting the presence or level of IMP3 in a primary cervical tumor of the subject over time, wherein an increase in the level of IMP3 in the primary tumor of the subject over time indicates that the in situ cancer is becoming invasive cancer. 
     
     
         14 . The method of  claim 13 , wherein the subject has a cervical squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN). 
     
     
         15 . The method of  claim 13 , wherein determining the presence or level of IMP3 comprises determining the presence or level of the IMP3 protein. 
     
     
         16 . The method of  claim 13 , wherein determining the presence or level of IMP3 comprises determining the presence or level of IMP3 RNA. 
     
     
         17 . A method for treating a subject having a cervical carcinoma, comprising
 (i) determining whether the level of IMP3 in a cervical tumor obtained from the subject is abnormally high; and if the level is high, excising the tumor and if the level is low or undetectable, not excising the tumor.   
     
     
         18 . The method of  claim 17 , wherein the excision is performed using the loop electrical excision procedure (LEEP). 
     
     
         19 . The method of  claim 17 , wherein the excision is performed using the cold knife cone excision procedure.