True L et al. (2006) A molecular correlate to the Gleason grading system for prostate adenocarcinoma. PNAS 103: 10991–10996

Gleason grade is an important parameter guiding therapy for prostate cancer. The Gleason score classifies tumors into categories on the basis of five histological patterns; patterns 3–5 have clinical significance, with pattern 5 representing the poorest cell differentiation. The molecular phenotype characterizing each grade could provide insight into the mechanisms involved in cancer progression. A microarray approach was, therefore, initiated to identify specific molecular 'fingerprints' associated with the different Gleason grades.

Using microdissection, cancer cells corresponding to the Gleason patterns 3, 4 and 5 were obtained from 29 radical prostatectomy samples. Transcript expression profiles for each cancer tissue sample were compared with the expression profile generated from a matched benign tissue sample. Using a supervised-learning approach, an 86-gene model with the ability to distinguish between low-grade (pattern 3) and high-grade (pattern 4/5) tumors was developed (patterns 4 and 5 were effectively indistinguishable at the molecular level). When applied to an independent set of 30 primary prostate carcinomas, the model successfully classified 76% of the samples. Several of the genes associated with prostate cancer grade discrimination possessed characteristics conducive to a role in cancer cell survival and invasion. Immunohistochemical quantification of independent tissue microarrays confirmed grade-associated levels of monoamine oxidase A and defender against cell death 1 proteins, both of which are involved in pathways associated with prostate cancer behavior.

The grade-discriminatory gene set identified in this experiment defines a pool of genes that could be involved in regulating the progression of prostate cancer; as such, these genes should be seen as potential targets for future pharmaceutical intervention.