Method to assess prognosis and to predict therapeutic success in cancer by determining hormone receptor expression levels

Abstract

The present invention is related to a method of classifying a sample of a patient who suffers from or being at risk of developing cancer, said method comprising the steps of determining in said sample from said patient, on a non protein basis, the expression level of at least one gene encoding for a hormone receptor selected from the group comprising estrogen receptor, progesterone receptor and/or androgen receptor in said sample; comparing the one or more expression level(s) determined with one or more expression level(s) of one or more reference genes, and classifying the sample of said patient from the outcome of the comparison into one of at least two classifications.

What is claimed is: 
     
         1 . A method of classifying a sample of a patient who suffers from or being at risk of developing cancer, said method comprising the steps of:
 a. determining in said sample from said patient, on a non protein basis, the expression level of at least one gene encoding for a hormone receptor selected from the group comprising estrogen receptor, progesterone receptor and/or androgen receptor in said sample;   b. comparing the one or more expression level(s) determined in step (a) with one or more expression level(s) of one or more reference genes; and   c. classifying the sample of said patient from the outcome of the comparison in step (b) into one of at least two classifications.   
     
     
         2 . The method according to  claim 1 , wherein a mode of treatment based on the classification in step (c) comprises a treatment targeting at least one hormone receptor selected from the group comprising estrogen receptor, progesterone receptor and/or androgen receptor, or targeting their respective signaling pathways, and/or a treatment targeting repair mechanisms related therewith. 
     
     
         3 . The method according to  claim 1  or  2 , characterized in that said treatment comprises the administration of tamoxifen. 
     
     
         4 . The method according to any of the aforementioned numbered paragraphs, characterized in that said treatment is intended to be given as hormone replacement therapy (HRT) in peri- or postmenopausal women. 
     
     
         5 . The method according to claim any of the aforementioned claims, characterized in that the gene encoding for the estrogen receptor is ESR1. 
     
     
         6 . A method according any of the aforementioned claims, characterized in that said one or more reference gene(s) is at least one housekeeping gene and/or at least one EMT marker gene. 
     
     
         7 . The method according to  claim 6 , wherein the at least one housekeeping gene is selected from the group comprising RPL37A, GAPDH, RPL 13 and/or HPRT1; and the at least one EMT marker gene is selected from the group comprising SNAI1, SNAI2 and/or SNAI3. 
     
     
         8 . The method according to any of the aforementioned claims, wherein the comparing step (b) is a ratio between the expression level of at least one hormone receptor and at least one EMT marker gene. 
     
     
         9 . The method according to any of the aforementioned claims, wherein the comparing step (b) is a ratio of ESR1 to SNAI2. 
     
     
         10 . The method according to any one of the aforementioned claims, wherein said expression level(s) is determined by
 a. a hybridization based method;   b. a PCR based method;   c. a method based on the electrochemical detection of particular molecules, and/or   d. an array based method.   
     
     
         11 . The method according to any one of the aforementioned claims, characterized in that said expression level is determined by reverse transcriptase polymerase chain reaction of RNA transcripts. 
     
     
         12 . The method according to  claim 10 , characterized in that said expression level is determined in formalin and/or paraffin fixed tissue samples of the RNA transcripts. 
     
     
         13 . The method according to any one of the aforementioned claims, wherein, after lysis, the sample is treated with silica-coated magnetic particles and a chaotropic salt, for purification of the nucleic acids contained in said sample prior to the determination in step (a). 
     
     
         14 . The method according to any one of the aforementioned claims, characterized in that said cancer displays characteristics of, or is, an adenocarcinoma. 
     
     
         15 . The method according to any one of the aforementioned claims, characterized in that said cancer is selected from the group comprising lung cancer, a non-small cell lung cancer (NSCLC), ovarian cancer; breast cancer and/or prostate cancer. 
     
     
         16 . The method according to any one of the aforementioned claims, wherein the expression level(s) determined in step (a) is/are correlated with said patient's data, said data being selected from the group consisting of etiopathology data, clinical symptoms, anamnesis data and/or data concerning the therapeutic regimen. 
     
     
         17 . An oligonucleotide comprising a nucleotide sequence which is a fragment, a fraction, a variant, a homologue, a derivative of, or a complementary to, any of the nucleic acid molecules set forth as SEQ ID NOs 1-9, or which is capable of hybridizing to a fragment, a fraction, a variant, a homologue, or a derivative of any of the nucleic acid molecules set forth as SEQ ID NOs 1-9. 
     
     
         18 . The oligonucleotide according to  claim 17 , wherein said oligonucleotide is selected from the group consisting of
 a. an amplification primer   b. a labeled probe, and/or   c. a substrate bound probe.   
     
     
         19 . A kit useful for carrying out a method of any one of the aforementioned claims, comprising at least one oligonucleotide according to  claim 17  and/or  18 .