Abstract:
Methods for diagnosing or detecting cancerous prostate tissue. A panel of 8 specific marker genes are provided. The overexpression of some of these marker genes compared to their expression in normal prostate tissue and the underexpression of the rest of these marker genes are indicative of cancerous prostate tissue. By using these 8 marker genes as a diagnostic tool, smaller tissue samples, such as those obtained by core needle biopsies can be used.

Description:
FIELD OF THE INVENTION  
       [0001]     The present invention relates to diagnosis methods and, more particularly, to diagnosis methods for detecting prostate cancer.  
       BACKGROUND TO THE INVENTION  
       [0002]     Prostate cancer is a leading cancer in men with 20,100 new cases expected in Canada in 2004 (Canadian Cancer Statistics, 2004). An even larger number of patients, following a positive PSA (prostate specific antigen) reading undergo an invasive biopsy but are not diagnosed with cancer. Unfortunately, invasive biopsy procedures require a long hospitalization with many possible side-effects. The reason for using the more invasive biopsy procedure, as opposed to the less invasive core needle biopsy is that the standard diagnostic procedure on core needle biopsy samples has not been proven to be as accurate as a more invasive biopsy and was thereby discarded as a diagnostic modality in several countries. Although the more invasive biopsies may provide a more accurate diagnosis, they are extremely traumatic for the patient. Moreover, such procedures can potentially result in long term disabilities and constitutes a significant cost to the health system.  
         [0003]     Current diagnostic techniques for detecting prostate cancer is based on the PSA level in the serum. The final diagnosis is determined by a pathologist checking for cancer cells in the biopsy samples.  
         [0004]     However, these present techniques are not perfect. The PSA level in the serum can be affected by factors other then cancer, including other pathologies and age. In addition, specific properties of PSA protein in serum make accurate concentration measurements very difficult. As a result, the PSA test has a large percentage of false positive as well as false negative readings. Therefore, biopsy samples are essential for more accurate diagnosis. Unfortunately, as noted above, the preferred method of biopsy, the core needle biopsy, is often inaccurate due to the very small sample size. However, genetic testing in core needle biopsy samples will allow for the accurate diagnosis without the need for more invasive methods.  
         [0005]     There is therefore a need for a more accurate diagnostic method that does not require an invasive biopsy to detect or diagnose prostate cancer. Ideally, such a method should be usable even with very small sample sizes and may be combined with other, pathologist-based diagnosis methods.  
       SUMMARY OF THE INVENTION  
       [0006]     The present invention provides methods for diagnosing or detecting cancerous prostate tissue. A panel of 8 specific marker genes are provided. The overexpression of some of these marker genes compared to their expression in normal prostate tissue and the underexpression of the rest of these marker genes are indicative of cancerous prostate tissue. By using these 8 marker genes as a diagnostic tool, smaller tissue samples, such as those obtained by core needle biopsies can be used.  
         [0007]     In a first aspect, the present invention provides a method for determining if prostate cells are cancerous, the method comprising:  
         [0008]     a) obtaining said prostate cells;  
         [0009]     b) determining if at least one specific gene is overexpressed or underexpressed in said prostate cells compared to an expression of said at least one specific gene in normal prostate cells;  
         [0010]     c) determining that said prostate cells are cancerous based on whether said at least one gene is overexpressed or underexpressed in said prostate cells.  
         [0011]     In another aspect, the present invention provides a use of at least one marker gene for identifying cancerous prostate tissue, an overexpression or underexpression of said at least one marker gene in prostate tissue compared to an expression of said at least one marker gene in normal prostate tissue being indicative of cancerous prostate tissue.  
         [0012]     Yet another aspect of the invention provides a method of diagnosing prostate cancer, the method comprising:  
         [0013]     a) obtaining prostate tissue to be diagnosed;  
         [0014]     b) determining if specific marker genes are overexpressed or underexpressed in said prostate tissue to be diagnosed compared to non-cancerous prostate tissue;  
         [0015]     c) determining if said prostate tissue to be diagnosed is cancerous based on an underexpression or overexpression of said specific marker genes. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0016]     A better understanding of the invention will be obtained by considering the detailed description below, with reference to the following drawings in which:  
         [0017]      FIG. 1  is an expression plot for the 8 genes which is the subject of the present invention;  
         [0018]      FIG. 2  is a boxplot of expression levels for the gene GSTM obtained over several experiments on prostate tissue;  
         [0019]      FIG. 3  is a boxplot of expression levels for the gene LTPB4 obtained over several experiments on prostate tissue;  
         [0020]      FIG. 4  is a boxplot of expression levels for the gene DF (adipsin) obtained over several experiments on prostate tissue;  
         [0021]      FIG. 5  is a boxplot of expression levels for the gene NELL2 obtained over several experiments on prostate tissue;  
         [0022]      FIG. 6  is a boxplot of expression levels for the gene XBP1 obtained over several experiments on prostate tissue;  
         [0023]      FIG. 7  is a boxplot of expression levels for the gene ITSN1 obtained over several experiments on prostate tissue;  
         [0024]      FIG. 8  is a boxplot of expression levels for the gene FOLH1 obtained over several experiments on prostate tissue; and  
         [0025]      FIG. 9  is a boxplot of expression levels for the gene Hepsin obtained over several experiments on prostate tissue.  
     
    
     DETAILED DESCRIPTION  
       [0026]     The present invention relates to the use of a panel of 8 specific marker genes to diagnose or detect cancerous prostate tissue. The panel of 8 marker genes are listed in Table 1 below. Experiments have shown that this panel of marker genes give high accuracy in prostate cancer diagnosis due to the expression levels of the marker genes in cancer tissue relative to their expression levels in normal tissue.  
         [0027]     The panel of 8 marker genes is given in Table 1. The marker genes were determined using a method developed by the inventors from the prostate tissues (normal and cancer) gene expression dataset obtained and described by Singh, D. et al. (Singh, D. et al. Gene expression correlates of clinical prostate cancer behaviour.  Cancer Cell  1:203 (2002)).  
                                     TABLE 1                           Panel of eight genes found to give high accuracy in prostate cancer diagnosis       and their expression level in cancer relative to normal tissue.                            Over or                       Underexpressed in       GeneBank               cancer tissue       Accession               relative to       Number   Gene Name   Symbol   UniGene ID   normal tissue               M96233   Glutathione S-transferase   GSTM4   Hs.348387   Underexpressed           M4       Y13622   Latent transforming   LTBP4   Hs.85087   Underexpressed           growth factor beta binding           protein 4       M84526   D component of   DF   Hs.155597   Underexpressed           complement (adipsin)       D83018   Nel-like 2   NELL2   Hs.79389   Overexpressed       Z93930   X-box binding protein 1   XBP1   Hs.149923   Overexpressed       AF064243   Intersectin 1 (SH3 domain   ITSN1   Hs.66392   Underexpressed           protein)       M99487   Folate hydrolase (Prostate   FOLH1   Hs.1915   Overexpressed           specific membrane antigen) 1       X07732   Hepsin (transmembrane   HPN   Hs.823   Overexpressed           protease, serine 1)                  
 
         [0028]     The genes listed above were derived using a microarray gene expression experiment, the gene expression plot being provided as  FIG. 1  for the 8 genes. For this expression plot, the samples are normal and tumour tissues.  
         [0029]      FIGS. 2-9  are boxplots of the comparative expression of the specific marker genes in normal prostate tissue, cancerous tissue, and other types of prostate tissue. The testing was done using the prostate microarray data available at the Oncomine database (see Rhodes D R, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, and Chinnaiyan A M. ONCOMINE: A Cancer Microarray Database and Data-Mining Platform. Neoplasia 2004); and Rhodes D R, Yu J, Shanker K, Deshpande N., Varambally R, Ghosh D, Barrette T, Pandey A, and Chinnaiyan A M, Large-Scale Meta-Analysis of Cancer Microarray Data Identifies Common Transcriptional Profiles of Neoplastic Transformation and Progression, PNAS (2004)).  
         [0030]     The dataset used for the experiments which resulted in the expression levels shown in the boxplots of  FIGS. 2-9  included gene expressions measured using Affymetrix technology on 52 prostate tumors and 50 non-tumor prostate samples. The pre-processing included threshold readjustment (floor 50, ceiling 16,000), filtering (max/min less than 5; max-min less than 50); logarithmic transformation and standardization (to mean of zero and variance of 1). The pre-processing resulted in the set comprising 6034 genes and 102 experiments. The microarray experiments were performed on prostate tumour samples and adjacent prostate tissue not containing tumour cells (selected by a pathologist based on cell morphology, referred to as “normal”) collected from patients undergoing radical prostatectomy at the Brigham and Women&#39;s Hospital, Boston, Mass. Each of these samples was reviewed by pathologist determining their Gleason Score (GS) as well as serum PSA. As noted above, microarray experiments were performed using GeneChip arrays (Affymetrix Inc.). Total RNA extracted from each sample was labeled with the fluorescence dye and hybridized to the slide in a one sample per slide format. Gene expression levels were obtained by measuring fluorescence intensities for each target (spot). Data pre-processing was performed using the standard protocol for GeneChip arrays (see Welsh J B., Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer.  Cancer Res.  61: 5974 (2001)) Data for each experiment was then scaled (normalized) to have overall mean of zero and standard deviation of one making data from different experiments comparable.  
         [0031]     Referring to  FIG. 2 , a boxplot of the expression levels for the gene GSTM4 obtained over several different experiments on prostate tissues is presented. Each box includes values for replicated experiments. The experiments included and the tissues used are summarized in Table 2:  
                           TABLE 2                       Experiment   C1   C2   P-value                   A1 [4]   BPH and Normal Prostate   Prostate Cancer   6.366       A2 [4]   Prostate Cancer   Metastatic Prostate   0.067               Cancer       A3 [4]   Prostate Cancer: Gleason 6   Prostate Cancer:   0.0823               Gleason 8       A4 [4]   Prostate Cancer: No PSA   Prostate Cancer:   0.8647           recur at 2 years   PSA recur       A5 [5]   Benign Prostatic   Prostate Cancer   0.1103           Hyperplasia                  
 
         [0032]     As can be seen from  FIG. 2  in conjunction with Table 2 above, the gene GSTM4 is underexpressed in cancerous prostate tissue when compared to its expression in normal prostate tissue (see experiment A1 in  FIG. 2 ). It can also be seen that, compared to the expression of this gene in normal prostate tissue, cancerous prostate tissue has a lower expression (see C1 in experiments A2-A4). Thus, for cancerous prostate tissue, the gene GSTM4 is underexpressed when compared to its expression in normal prostate tissue.  
         [0033]     Referring to  FIG. 3 , a boxplot of expression levels for the gene LTPB4 obtained over several different experiments on prostate tissues is illustrated. Each box includes values for replicated experiments. The experiments included and the tissues used are summarized in Table 3 below:  
                           TABLE 3                       Experiment   C1   C2   P-value                   A1 [4]   BPH and Normal   Prostate Cancer   0.0872           Prostate       A2 [4]   Prostate Cancer   Metastatic Prostate   0.0069               Cancer       A3 [4]   Prostate Cancer:   Prostate Cancer:   0.1896           Gleason 6   Gleason 8       A4 [4]   Prostate Cancer: No PSA   Prostate Cancer:   0.7115           recur at 2 years   PSA recur       A5 [6]   Normal Prostate   Prostate Cancer   0.1142       A6 [6]   Prostate Cancer   Metastatic Prostate   1.2e−5               Cancer       A7 [7]   Normal Prostate   Prostate Cancer   0.158        A8 [5]   Benign Prostatic   Prostate Cancer   0.0404           Hyperplasia       A9 [8]   Normal Prostate   Prostate Cancer   1.459        A10 [8]   Prostate Cancer   Metastatic Prostate   0.7855               Cancer       A11 [9]   No PSA recurrence at 3   PSA Recurrence at   0.6524           years   3 years       A12 [9]   Nontumor Prostate   Prostate Cancer   3.7e−5       A13 [9]   Prostate Cancer:   Prostate Cancer:   0.3183           Gleason 6   Gleason 8, 9       A14 [10]   Normal Prostate   Prostate Cancer   6.4e−6       A15 [10]   Prostate Cancer:   Prostate Cancer:   0.6032           Gleason 6   Gleason 8, 9                  
 
         [0034]     The results illustrated in  FIG. 3  show that the gene LTPB4 is underexpressed in cancerous prostate tissue when compared to its expression in normal prostate tissue. The results of experiments A1, A5, A7, A9, A12, and A14 show that, compared to its expression in normal prostate tissue, the gene LTPB4 is underexpressed in cancerous prostate tissue. For prostate cancer tissue, the gene LTPB4 is therefore underexpressed when compared to its expression in normal prostate tissue.  
         [0035]     Referring to  FIG. 4 , such is a boxplot of expression levels for the gene DF (adipsin) obtained over several different experiments on prostate tissues. Each box includes values for replicated experiments. The experiments and the prostate tissue included in the experiments are summarized in Table 4 below:  
                                             TABLE 4                       Experiment   C1   C2   P-value                                A1 [4]   BPH and Normal   Prostate Cancer   0.4053           Prostate       A2 [4]   Prostate Cancer   Metastatic Prostate   0.7189               Cancer       A3 [4]   Prostate Cancer:   Prostate Cancer:   0.044           Gleason 6   Gleason 8       A4 [4]   Prostate Cancer: No   Prostate Cancer:   0.7859           PSA recur at 2 years   PSA recur       A5 [6]   Normal Prostate   Prostate Cancer   0.0006       A6 [6]   Prostate Cancer   Metastatic Prostate   0.013               Cancer       A7 [7]   Normal Prostate   Prostate Cancer   0.0642       A8 [11]   Normal Prostate   Prostate Cancer   0.6993       A9 [8]   Normal Prostate   Prostate Cancer   0.0893       A10 [8]   Prostate Cancer   Metastatic Prostate   0.0031               Cancer       A11 [9]   No PSA recurrence   PSA Recurrence at 3   0.0518           at 3 years   years       A12 [9]   Nontumor Prostate   Prostate Cancer   6.4e−10       A13 [9]   Prostate Cancer:   Prostate Cancer:   0.2172           Gleason 6   Gleason 8, 9       A14 [10]   Normal Prostate   Prostate Cancer   0.118       A15 [10]   Prostate Cancer:   Prostate Cancer:   0.9273           Gleason 6   Gleason 8, 9                  
 
         [0036]     The results in  FIG. 4  show that the gene DF (adipsin) is underexpressed in cancerous prostate tissue compared to its expression in normal prostate tissue. As can be seen from the results in experiments A1, A5, A7-A9, A12, and A14, the gene DF (adipsin) has much lower expression levels in cancerous prostate tissue than in normal prostate tissue.  
         [0037]     Referring to  FIG. 5 , a boxplot of expression levels for gene NELL2 obtained over several different experiments on prostate tissues is illustrated. Each box includes values for replicated experiments. The experiments and the types of prostate tissue used in the experiments are summarized in Table 5 below:  
                           TABLE 5                       Experiment   C1   C2   P-value                   A1 [4]   BPH and Normal   Prostate Cancer   0.0039           Prostate       A2 [4]   Prostate Cancer   Metastatic Prostate   0.0339               Cancer       A3[4]   Prostate Cancer:   Prostate Cancer:   0.3201           Gleason 6   Gleason 8       A4 [4]   Prostate Cancer:   Prostate Cancer: PSA   0.3781           No PSA recur at 2   recur           years       A5 [6]   Normal Prostate   Prostate Cancer   0.0041       A6 [6]   Prostate Cancer   Metastatic Prostate   0.0018               Cancer       A7 [7]   Normal Prostate   Prostate Cancer   0.9941       A8 [5]   Benign Prostatic   Prostate Cancer   4.10E−06           Hyperplasia       A9 [11]   Normal Prostate   Prostate Cancer   0.3558       A10 [8]   Normal Prostate   Prostate Cancer   0.0009       A11 [8]   Prostate Cancer   Metastatic Prostate   0.832                Cancer       A12 [9]   No PSA recurrence   PSA Recurrence at 3   0.0291           at 3 years   years       A13 [9]   Nontumor Prostate   Prostate Cancer   1.20E−12       A14 [9]   Prostate Cancer:   Prostate Cancer:   0.8026           Gleason 6   Gleason 8, 9       A15 [10]   Normal Prostate   Prostate Cancer   0.1714       A16 [10]   Prostate Cancer:   Prostate Cancer:   0.6622           Gleason 6   Gleason 8, 9                  
 
         [0038]     The results in  FIG. 5  illustrate that the gene NELL2 is overexpressed in cancerous prostate tissue when compared to its expression in non-cancerous prostate tissue. The results for the experiments A1, A5, A7, A9, A10, A13, and A14 show that the gene NELL2 has a higher expression in cancerous prostate tissue than in normal prostate tissue.  
         [0039]     Referring to  FIG. 6 , a boxplot of expression levels for gene XBP1 obtained over several different experiments on prostate tissues is illustrated. Each box includes values for replicated experiments. The experiments and the types of prostate tissue used are summarized in Table 6 below:  
                           TABLE 6                       Experiment   C1   C2   P-value                   A1 [4]   BPH and Normal   Prostate Cancer   0.0042           Prostate       A2 [4]   Prostate Cancer   Metastatic Prostate   1.00E−04               Cancer       A3 [4]   Prostate Cancer:   Prostate Cancer:   0.0456           Gleason 6   Gleason 8       A4 [4]   Prostate Cancer: No   Prostate Cancer: PSA   0.0581           PSA recur at 2 years   recur       A5 [7]   Normal Prostate   Prostate Cancer   0.5674       A6 [5]   Benign Prostatic   Prostate Cancer   0.8723           Hyperplasia       A7 [11]   Normal Prostate   Prostate Cancer   0.8965       A8 [8]   Normal Prostate   Prostate Cancer   0.428        A9 [8]   Prostate Cancer   Metastatic Prostate   0.0697               Cancer                  
 
         [0040]      FIG. 6  shows that the gene XBP1 is overexpressed in cancerous prostate tissue as opposed to normal prostate tissue. Experiments A1, A4, A5, A7 and A8 illustrate that the gene XBP1 has a lower expression level in normal prostate tissue than in cancerous prostate tissue.  
         [0041]     Referring to  FIG. 7 , a boxplot of expression levels for gene ITSN1 obtained over several different experiments on prostate tissues is illustrated. Each box includes values for replicated experiments. The experiments and the various tissues used are summarized in Table 7 below:  
                           TABLE 7                       Experiment   C1   C2   P-value                   A1 [4]   BPH and Normal Prostate   Prostate Cancer   0.0024       A2 [4]   Prostate Cancer   Metastatic   0.0106               Prostate Cancer       A3 [4]   Prostate Cancer: Gleason 6   Prostate Cancer:   0.2204               Gleason 8       A4 [4]   Prostate Cancer: No PSA   Prostate Cancer:   0.6537           recur at 2 years   PSA recur       A5 [6]   Normal Prostate   Prostate Cancer   0.3049       A6[6]   Prostate Cancer   Metastatic   0.0051               Prostate Cancer       A7 [7]   Normal Prostate   Prostate Cancer   0.2124       A8 [5]   Benign Prostatic   Prostate Cancer   0.0021           Hyperplasia       A9 [9]   No PSA recurrence at 3   PSA Recurrence   0.6691           years   at 3 years       A10 [9]   Nontumor Prostate   Prostate Cancer   3.50E−10       A11 [9]   Prostate Cancer: Gleason 6   Prostate Cancer:   0.2232               Gleason 8, 9       A12 [10]   Normal Prostate   Prostate Cancer   0.0003       A13 [10]   Prostate Cancer: Gleason 6   Prostate Cancer:   0.586                Gleason 8, 9                  
 
         [0042]      FIG. 7  illustrates that the gene ITSN1 has a lower expression in cancerous prostate tissue when compared to its expression in normal prostate tissue. As can be seen from the results of experiments A1, A5, A7, A10, and A12, cancerous prostate tissue has lower expression levels of ITSN1 when compared to non-cancerous prostate tissue.  
         [0043]     Referring to  FIG. 8 , a boxplot of expression levels for gene FOLH1 obtained over several different experiments on prostate tissues is illustrated. Each box includes values for replicated experiments. The experiments and the tissues used are summarized in Table 8 below:  
                                             TABLE 8                       Experiment   C1   C2   P-value                                A1 [4]   BPH and Normal   Prostate Cancer   0.0011           Prostate       A2 [4]   Prostate Cancer   Metastatic Prostate   0.07               Cancer       A3 [4]   Prostate Cancer:   Prostate Cancer:   0.3748           Gleason 6   Gleason 8       A4 [4]   Prostate Cancer: No   Prostate Cancer: PSA   0.0801           PSA recur at 2 years   recur       A5 [6]   Normal Prostate   Prostate Cancer   0.0047       A6 [6]   Prostate Cancer   Metastatic Prostate   0.2598               Cancer       A7 [7]   Normal Prostate   Prostate Cancer   0.0059       A8 [5]   Benign Prostatic   Prostate Cancer   0.0152           Hyperplasia       A9 [11]   Normal Prostate   Prostate Cancer   0.3939       A10 [8]   Normal Prostate   Prostate Cancer   0.8983       A11 [8]   Prostate Cancer   Metastatic Prostate   0.0123               Cancer       A12 [10]   Normal Prostate   Prostate Cancer   0.0039       A13 [10]   Prostate Cancer:   Prostate Cancer:   0.2576           Gleason 6   Gleason 8, 9                  
 
         [0044]      FIG. 8  illustrates that the gene FOLH1 is overexpressed in cancerous prostate tissue as compared to normal prostate tissue. The results of experiments A1, A5, A7, A9, A10, and A12 show that the gene FOLH1 has a higher expression in cancerous prostate tissue than in normal prostate tissue.  
         [0045]     Referring to  FIG. 9 , a boxplot of expression levels for gene Hepsin obtained over several different experiments on prostate tissues is illustrated. Each box includes values for replicated experiments. The experiments and the different types of prostate tissue used are summarized in Table 9 below:  
                           TABLE 9                       Experiment   C1   C2   P-value                   A1 [4]   BPH and Normal   Prostate Cancer   1.60E−08           Prostate       A2 [4]   Prostate Cancer   Metastatic Prostate   0.3311               Cancer       A3 [4]   Prostate Cancer:   Prostate Cancer:   0.8772           Gleason 6   Gleason 8       A4 [4]   Prostate Cancer: No   Prostate Cancer:   0.5244           PSA recur at 2 years   PSA recur       A5 [6]   Normal Prostate   Prostate Cancer   0.0205       A6 [6]   Prostate Cancer   Metastatic Prostate   0.0351               Cancer       A7 [7]   Normal Prostate   Prostate Cancer   0.0017       A8 [5]   Benign Prostatic   Prostate Cancer   1.80E−07           Hyperplasia       A9 [8]   Normal Prostate   Prostate Cancer   0.0484       A10 [8]   Prostate Cancer   Metastatic Prostate   0.0662               Cancer       A11 [9]   No PSA recurrence at 3   PSA Recurrence at   0.866            years   3 years       A12 [9]   Nontumor Prostate   Prostate Cancer   6.10E−25       A13 [9]   Prostate Cancer:   Prostate Cancer:   0.2081           Gleason 6   Gleason 8, 9       A14 [10]   Normal Prostate   Prostate Cancer   2.10E−08       A15 [10]   Prostate Cancer:   Prostate Cancer:   0.7475           Gleason 6   Gleason 8, 9                  
 
         [0046]     From  FIG. 9 , it can be seen that the gene Hepsin is overexpressed in cancerous prostate tissue as opposed to normal prostate tissue. The results of experiments A1, A5, A7, A8, A9, A12, and A14 show that Hepsin has a higher expression in cancerous prostate tissue than in normal prostate tissue.  
         [0047]     The qualitative agreement between the differences in expression in cancer and normal prostate tissues for the eight genes investigated here is good overall with most genes showing significant difference between cancer and normal tissue as well as benign and malignant tumours in the majority of experiments. The results shown here prove that a subset of 8 genes is an appropriate diagnostic panel regardless of the experimental conditions. At the same time, in some cases, especially for the gene LTPB4, there are changes in the relative expression in cancer against normal prostate tissue depending on the experiment. Such variations show that it is preferable that one looks at the overall result for the whole panel and that diagnostics based on only one gene may be unreliable.  
         [0048]     It should be noted that expression analysis can be carried out using any method for measuring gene expression. Such methods as microarrays, diagnostic panel mini-chip, PCR, real-time PCR, and other similar methods may be used. Similarly, methods for measuring protein expression may also be used.  
         [0049]     As noted above, the cancerous prostate cells can be obtained from a patient using needle biopsy or even from prostate cancer cells present in the blood stream. Normal or non-cancerous prostate cells against which the cancerous cells can be compared can also be obtained from the patient or from other patients. Experiments have shown that the diagnosis can be possible from just a small number of cancer cells.  
         [0050]     While it is preferable that the complete panel of 8 marker genes be used in the diagnosis of possible prostate cancer, using a subset of the 8 marker genes will also yield useful results. Using a panel of anywhere from 1 to 7 marker genes out of the 8 marker genes on suspect prostate tissue will still provide a useful indication as to whether cancerous prostate tissue may be present or whether further and more involved tests are required.  
         [0051]     A person understanding this invention may now conceive of alternative structures and embodiments or variations of the above all of which are intended to fall within the scope of the invention as defined in the claims that follow.