Molecular disorders in transitional vs. peripheral zone prostate adenocarcinoma.
Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been shown to be mechanisms for tumor-suppressor gene inactivation in human oncogenesis. In our study, we examined LOH and MSI using 16 polymorphic markers of DNA for chromosomes 1, 3, 7, 8, 10 and 11. Microdissected tumor samples were isolated from 32 patients, representing 11 foci of incidentally discovered prostate cancer of the transitional zone (TZ), 12 prostate cancer of the peripheral zone (PZ) and 10 of high-grade PIN. We found loss of heterozygosity in the TZ group in 91% of informative cases (10/11) with al least 1 marker compared to 58% of cases (7/12) in PZ group and 70% of cases (7/10) in the HGPIN group. Chromosome 7 showed the highest rate of allelic loss in all 3 categories, with loss of 43% of loci in PIN, 37% in TZ tumors and 31% in PZ tumors. At chromosome 11, LOH was detected in 26% of loci in the TZ group, in 7% of loci in the PZ group and in 13% of loci in the PIN group. On chromosome 8, the PZ and HGPIN group showed allelic loss in 22% and 21% of loci, respectively, compared to 10% detected in the TZ group. The TZ group showed a significant higher rate of allelic instability compared to that observed in tumor samples from the peripheral zone: 73% of cases (8/11) showed genetic alterations (RER+ phenotype) in at least 4 loci analyzed compared to 8% and 10% in the PZ and HGPIN groups, respectively (p = 0.0006). These data suggest that transitional zone carcinoma and peripheral zone carcinoma display distinct and specific genetic alterations in different chromosomes. This diversity may help explain biologic and clinical differences between carcinomas arising in these distinct zones of the prostate. Also our results strongly suggest that the RER+ mutator phenotype could be linked to early development of transitional zone prostate carcinoma.
Colombo
P
P
Department of Pathology, Humanitas Clinical Institute of Rozzano, Milan, Italy. piergiuseppe.colombo@humanitas.it
Patriarca
C
C
Alfano
R M
RM
Cassani
B
B
Ceva Grimaldi
G
G
Roncalli
M
M
Bosari
S
S
Coggi
G
G
Campo
B
B
Gould
V E
VE
D000230:Adenocarcinoma / Q000235:genetics*; D000483:Alleles; D002880:Chromosomes, Human, Pair 11; D002897:Chromosomes, Human, Pair 7; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
D005819:Genetic Markers