title: Molecular analysis of multifocal prostate cancer by comparative genomic hybridization.
abstract: 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.
authors.affiliation: Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Haruna
authors.initials: H
authors.lastname: Ishida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shindo
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Niwa
authors.forename: Mika
authors.initials: M
authors.lastname: Kino
authors.forename: Koji
authors.initials: K
authors.lastname: Kawamura
authors.forename: Naoto
authors.initials: N
authors.lastname: Kamiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Imamoto
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hirokawa
authors.forename: Taizo
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanizawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ichikawa
mesh_terms: 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