Gene Expression Profiling in Biopsied Tumor Tissues

Abstract

The invention concerns sensitive methods to measure mRNA levels in biopsied tumor tissues, including archived paraffin-embedded biopsy material. The invention also concerns breast cancer gene sets important in the diagnosis and treatment of breast cancer, and methods for assigning the most optimal treatment options to breast cancer patient based upon knowledge derived from gene expression studies.

1 .- 45 . (canceled) 
     
     
         46 . A method comprising:
 assaying a level of a RNA transcript of CEGP1 in a tissue sample obtained from a primary ductal or lobular breast tumor of a human patient;   normalizing said level against a level of at least one reference RNA transcript in said tissue sample to provide a normalized CEGP1 expression level; and   predicting the likelihood of long-term survival of said patient without recurrence of breast cancer by comparing said normalized CEGP1 expression level to CEGP1 expression data obtained from reference breast cancer samples,   wherein an increased normalized CEGP1 expression level is positively correlated with an increased likelihood of long-term survival without breast cancer recurrence in said patients.   
     
     
         47 . The method of  claim 46  further comprising assaying a level of a RNA transcript of one or more genes selected from the group consisting of: STK15, Ki-67, PR, GSTM3, ESR1, HNF3A, BIRC5, BAG1, BCL2, CCNB1, and GSTM1 in said tissue sample;
 normalizing the level of the RNA transcript of the one or more genes against a level of at least one reference RNA transcript in said tissue sample to provide a normalized level of said one or more genes; and   comparing said normalized level of said one or more genes to gene expression data from said one or more genes obtained from reference breast cancer samples,   wherein increased expression of one or more of BIRC5, CCNB1, STK15 and Ki-67, negatively correlates with an increased likelihood of long-term survival without breast cancer recurrence, and increased expression of one or more of BAG1, BCL2, PR, GSTM1, GSTM3, ESR1 and HNF3A positively correlates with an increased likelihood of long-term survival without breast cancer recurrence.   
     
     
         48 . The method of  claim 46  wherein the breast tumor is an invasive breast tumor, and said method further comprises assaying a level of a RNA transcript of one or more genes selected from the group consisting of: FOXM1, PRAME, BCL2, STK15, Ki-67, PR, BBC3, NME1, BIRC5, GATA3, TFRC, YB-1, DPYD, CA9, Contig51037, RPS6K1 and Her2 in said tissue sample. 
     
     
         49 . The method of  claim 46  wherein said breast tumor is estrogen receptor (ER) positive breast tumor. 
     
     
         50 . The method of  claim 49  further comprising assaying a level of a RNA transcript of one or more genes selected from the group consisting of: PRAME, BCL2, FOXM1, DIABLO, EPHX1, HIF1A, VEGFC, Ki-67, IGF1R, VDR, NME1, GSTM3, Contig51037, CDC25B, CTSB, p27, CDH1, and IGFBP3 in said tissue sample. 
     
     
         51 . The method of  claim 47  wherein the levels of 2 or more RNA transcripts are assayed. 
     
     
         52 . The method of  claim 46 , wherein said tissue sample is a fixed,
 wax-embedded breast cancer tissue specimen of said patient.   
     
     
         53 . The method of  claim 46 , wherein said tissue sample is from a fine needle biopsy. 
     
     
         54 . The method of  claim 46 , further comprising creating a report based upon the normalized CEGP1 expression level. 
     
     
         55 . The method of  claim 54 , wherein said report includes a prediction of the likelihood of long term survival of said patient without the recurrence of breast cancer. 
     
     
         56 . The method of  claim 55 , wherein said report comprises information concerning a recommendation for a treatment modality of said patient. 
     
     
         57 . The method of  claim 46 , wherein said gene expression data is produced using a multivariate analysis using the Cox Proportional Hazards model. 
     
     
         58 . The method of  claim 46  wherein said assaying is done by reverse transcriptase polymerase chain reaction (RT-PCR). 
     
     
         59 . The method of  claim 46 , wherein said assaying is done after a primary ductal carcinoma has been surgically removed from a breast of said patient. 
     
     
         60 . The method of  claim 59 , wherein said primary ductal carcinoma is an invasive ductal carcinoma. 
     
     
         61 . The method of  claim 46 , wherein said assaying is done after a primary lobular carcinoma has been surgically removed from a breast of said patient. 
     
     
         62 . The method of  claim 61 , wherein said primary lobular carcinoma is an invasive lobular carcinoma.