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.
Rights and permissions
About this article
Cite this article
Microarray approach identifies genes potentially involved in prostate cancer progression. Nat Rev Clin Oncol 3, 528 (2006). https://doi.org/10.1038/ncponc0598
Issue Date:
DOI: https://doi.org/10.1038/ncponc0598