title: Loss of p53 and c-myc overrepresentation in stage T(2-3)N(1-3)M(0) prostate cancer are potential markers for cancer progression.
abstract: To determine whether genetic changes are markers of cancer progression and patient survival in Stage T(2-3)N(1-3)M(0) prostatic carcinoma, we compared 26 patients who died of tumor relapse after prostatectomy and lymphadenectomy (case group) with 26 matched patients who were alive at the time of the matched case's death (control group). Nine unmatched cases were also included in this study. In 37 cases, paired primary tumors (119 foci) and lymph node metastases (114 foci) were available for study. Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, and 17 and region-specific probes for D7S486 (7q31), c-myc (8q24), LPL (8p22), and p53 (17p13) was performed on available primary carcinomas and lymph node metastases. In primary tumor foci, +7q31, -8p22, +c-myc, substantial additional increases of myc (AI-c-myc), and -p53 were observed in 65%, 74%, 43%, 29%, and 31% of foci, respectively. AI-c-myc was strongly associated with higher cancer Gleason score (P =.003). Heterogeneity of genetic changes was frequently observed among multiple cancer foci. Lymph node metastases of prostate cancer usually shared genetic changes with paired primary tumors. In addition, the genetic change pattern with -8p, +c-myc or AI-c-myc, +7q, and +p53 was slightly higher in lymph node metastases (22%) than in primary tumors (6%) (P =.08). In matched case and control patients, simultaneous gain of 7q31 (+7q31) and CEP7 (+CEP7) was identified in 59% and 68% of specimens for case and control groups, respectively (P =.48). Loss of 8p22 (-8p22) was identified in 77% and 69% of specimens for case and control groups, respectively (P = 1.0). Simultaneous gain of c-myc (+c-myc) and CEP8 (+CEP8) without overt additional increase of c-myc copy number relative to CEP8 copy number, was identified in 38% and 54% of specimens for case and control groups, respectively (P =.27). AI-c-myc was identified in 54% and 23% of specimens for case and control groups, respectively (odds ratio = 3.0, P =.06). Loss of p53 (-p53) was identified in 46% and 15% of specimens for case and control groups, respectively (odds ratio = 4.0, P =.04). Our results indicate that FISH anomalies are very common in both primary tumors and lymph node metastases of Stage T(2-3)N(1-3)M(0) prostate cancer; that AI-c-myc is associated with higher cancer Gleason score; that AI-c-myc and -p53 are associated with prostate cancer progression and are potential markers of survival in Stage T(2-3)N(1-3)M(0) prostate cancer; and that lymph node metastases usually have similar or additional genetic changes compared with primary tumors, and multiple lymph node metastases usually have similar genetic changes.
authors.affiliation: Department of Laboratory Medicine and Pathology, Section of Biostatistics, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Junqi
authors.initials: J
authors.lastname: Qian
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirasawa
authors.forename: David G
authors.initials: DG
authors.lastname: Bostwick
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Bergstralh
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Slezak
authors.forename: Kari L
authors.initials: KL
authors.lastname: Anderl
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Borell
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lieber
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000556:secondary; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D015331:Cohort Studies; D018450:Disease Progression; D016259:Genes, myc; D016158:Genes, p53; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies
chemical_list: D005819:Genetic Markers