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Molecular disorders in transitional vs. peripheral zone prostate adenocarcinoma
P Colombo1, C Patriarca, R M Alfano
1Department of Pathology, Humanitas Clinical Institute of Rozzano, Milan, Italy. piergiuseppe.colombo@humanitas.it
International Journal of Cancer
|December 18, 2001
Summary
Prostate cancer in the transitional zone shows significantly higher genetic instability than in the peripheral zone, suggesting distinct molecular pathways. The RER+ mutator phenotype may be linked to early transitional zone prostate cancer development.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Loss of heterozygosity (LOH) and microsatellite instability (MSI) are key mechanisms in tumor suppressor gene inactivation during oncogenesis.
- Prostate cancer exhibits distinct biological and clinical behaviors, potentially linked to its anatomical origins within the prostate gland.
Purpose of the Study:
- To investigate and compare LOH and MSI patterns in prostate cancer originating from the transitional zone (TZ) versus the peripheral zone (PZ).
- To identify specific chromosomal alterations associated with high-grade prostatic intraepithelial neoplasia (HGPIN) and different prostate cancer zones.
Main Methods:
- Analysis of LOH and MSI using 16 polymorphic DNA markers across chromosomes 1, 3, 7, 8, 10, and 11.
- Examination of microdissected tumor samples from 32 patients, including TZ prostate cancer, PZ prostate cancer, and HGPIN.
Main Results:
- The TZ group exhibited a significantly higher rate of LOH (91%) compared to the PZ group (58%) and HGPIN group (70%).
- Chromosome 7 showed the highest allelic loss rates across all categories (PIN 43%, TZ 37%, PZ 31%).
- The TZ group displayed a markedly higher frequency of the RER+ mutator phenotype (73%) compared to PZ (8%) and HGPIN (10%) groups, indicating substantial allelic instability.
Conclusions:
- Transitional zone and peripheral zone prostate carcinomas demonstrate distinct genetic alterations on specific chromosomes.
- These zone-specific genetic differences may underlie the observed variations in prostate cancer biology and clinical presentation.
- The RER+ mutator phenotype is strongly implicated in the early development of transitional zone prostate carcinoma.