Method of determining a chemotherapeutic regimen based on glutathione-s-transferase pi expression

Abstract

The present invention relates to prognostic methods which are useful in medicine, particularly cancer chemotherapy. The object of the invention to provide a method for assessing GST-pi expression levels in fixed or fixed and paraffin embedded tissues and prognosticate the probable resistance or sensitivity of a patient's tumor to treatment with platinum-based therapies by examination of the amount of GST-pi mRNA in a patient's tumor cells and comparing it to a predetermined threshold expression level. More specifically, the invention provides to oligonucleotide primer pair GST-piand methods comprising their use for detecting levels of GST-pi mRNA.

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         15 . A method for determining a platinum-based chemotherapeutic regimen for treating a tumor in a patient comprising: 
 (a) obtaining a tissue sample of the tumor and fixing the sample, to obtain a fixed tumor sample;    (b) isolating mRNA from the fixed tumor sample by heating the fixed tumor sample in the presence of an effective concentration of a chaotropic agent wherein the heating occurs at a temperature from about 75° C. to about 100° C. for a time period of about 5 to about 120 minutes;    (c) subjecting the mRNA to amplification using a pair of oligonucleotide primers capable of amplifying a region of the GST-pi gene, to obtain an amplified sample;    (d) determining the amount of GST-pi mRNA in the amplified sample;    (e) comparing the amount of GST-pi mRNA from step (d) to an amount of mRNA of an internal control gene to obtain a relative GST-pi expression level; and    (f) determining a platinum-based chemotherapeutic regimen based on the relative GST-pi expression level in the amplified sample and a predetermined threshold level for GST-pi gene expression.    
     
     
         16 . The method of  claim 15  wherein the tumor is an esophogeal adenocarcinaoma tumor.  
     
     
         17 . A method for determining a platinum-based chemotherapeutic regimen for treating a tumor in a patient comprising: 
 (a) obtaining a tissue sample of the tumor and fixing the sample, to obtain a fixed tumor sample;    (b) isolating mRNA from the fixed tumor sample by heating the fixed tumor sample in the presence of an effective concentration of a chaotropic agent wherein the heating occurs at a temperature from about 75° C. to about 100° C. for a time period of about 5 to about 120 minutes;    (c) determining the amount of GST-pi mRNA in the fixed tumor sample;    (d) comparing the amount of GST-pi mRNA from step (c) to an amount of mRNA of an internal control gene in the fixed tumor sample to obtain a relative GST-pi expression level; and    (e) determining a platinum-based chemotherapeutic regimen based on the relative GST-pi expression level in the fixed tumor sample and a predetermined threshold level for GST-pi gene expression.    
     
     
         18 . The method of  claim 17  wherein the tumor is an esophageal adenocarcinoma tumor.