Molecular disorders in transitional vs. peripheral zone prostate adenocarcinoma

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.