Molecular analysis of multifocal prostate cancer by comparative genomic hybridization.
BACKGROUND
Prostate cancer is often multifocal and shows histological heterogeneity among different tumor foci within the same prostate. We analyzed the origin and molecular basis of multifocal prostate cancer and genomic alterations associated with tumor progression.


METHODS
We examined 45 multifocal prostate cancer foci from 22 radical prostatectomy specimens by comparative genomic hybridization (CGH). Laser capture microdissection (LCM) was used to gather cancer cells from frozen prostate specimens.


RESULTS
Frequent chromosomal alternations were losses of 2q21-24 (22.2%), 6q14-22 (60.0%), 8p12-22 (35.6%), 13q14-31 (44.4%) and 16q13-24 (24.4%) and gains of 8q21.3-24.3 (37.8%) and 7q21-33 (20.0%). Frequency of losses of 8p12-22 and 16q13-24 and gains of 8q21.3-24.3 were significantly higher in tumors with high Gleason score (GS) than in those with low GS (P < 0.01, P < 0.05, and P < 0.01, respectively). Tumors with losses of 8p12-22 or 13q14-31 displayed larger volume than those without such losses (P < 0.05 and P < 0.01, respectively). In comparison between different tumor foci within the same prostate, chromosomal alterations did not show completely the same pattern between any tumor foci, except for one case in which two of the three foci displayed no chromosomal abnormalities. More malignant tumors (high GS or extracapsular invasion) displayed significantly higher frequency of losses of 8p12-22 (P < 0.05).


CONCLUSIONS
These results suggest that tumor foci within the same prostate represent independent tumors with differing clonal origin and that loss of 8p12-22 represents an important determinant of prostate cancer progression.
Kobayashi
Masayuki
M
Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Ishida
Haruna
H
Shindo
Takayuki
T
Niwa
Shin-Ichiro
S
Kino
Mika
M
Kawamura
Koji
K
Kamiya
Naoto
N
Imamoto
Takashi
T
Suzuki
Hiroyoshi
H
Hirokawa
Yoshifumi
Y
Shiraishi
Taizo
T
Tanizawa
Tohru
T
Nakatani
Yukio
Y
Ichikawa
Tomohiko
T
D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization / Q000379:methods*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000601:surgery; D012189:Retrospective Studies