title: Aneusomy of chromosomes 7, 8, and 17 and amplification of HER-2/neu and epidermal growth factor receptor in Gleason score 7 prostate carcinoma: a differential fluorescent in situ hybridization study of Gleason pattern 3 and 4 using tissue microarray.
abstract: Recent evidence shows that the proportion of poorly differentiated prostate carcinoma (Gleason pattern [GP] 4/5) is a surrogate factor for biochemical failure after radical prostatectomy (RP). However, little is known about specific molecular and cytogenetic changes in this aggressive component of localized prostate cancer. We constructed a tissue microarray containing areas of GP 3 and 4 from formalin-fixed radical prostatectomy specimens of 39 patients with Gleason score 7 carcinoma (>or=50% GP 4), known pathologic staging parameters (stage < T3b), and biochemical failure data (mean follow-up, 30 months; range, 5 to 74 months). Interphase fluorescent in situ hybridization (FISH) was performed on 5-microm microarray sections using pericentromeric probes to chromosomes 7, 8, and 17 and probes for the HER-2/neu and epidermal growth factor receptor (EGFR) genes. Low-level amplification of HER-2/neu was found in 26% of cases (3 to 5 signals per nucleus, corrected for chromosome 17 aneusomy). Aneusomy of chromosomes 7, 8, and 17 was identified in 21%, 15%, and 5% of cases, respectively. All aberrations occurred almost exclusively in GP 4 carcinoma (8 of 8 aneusomies 7, 2 of 2 trisomies 17, 9 of 10 HER-2/neu amplifications, and 5 of 6 aneusomies 8; P < .001). The presence of HER-2/neu amplification was associated with high tumor volume (>2.0 cm(3), P = 0.004). Among patients with negative surgical margins, gain of chromosome 7 was associated with biochemical failure after RP (P =.004, log-rank). Amplification of the EGFR gene occurred in only 1 case (3%). Significant differences in HER-2/neu amplification and gain of chromosomes 7, 8, and 17 were detected between GP 4 prostate carcinoma and GP 3. The frequency of aberrations increased with tumor volume. Chromosome 7 abnormalities may play an important role in cancer progression in margin-negative patients. EGFR amplification was rare, suggesting that this oncogene is not altered at the gene copy number level.
authors.affiliation: Department of Anatomic, The Urology Institute, the Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: M
authors.initials: M
authors.lastname: Skacel
authors.forename: A H
authors.initials: AH
authors.lastname: Ormsby
authors.forename: J D
authors.initials: JD
authors.lastname: Pettay
authors.forename: E K
authors.initials: EK
authors.lastname: Tsiftsakis
authors.forename: L S
authors.initials: LS
authors.lastname: Liou
authors.forename: E A
authors.initials: EA
authors.lastname: Klein
authors.forename: H S
authors.initials: HS
authors.lastname: Levin
authors.forename: C D
authors.initials: CD
authors.lastname: Zippe
authors.forename: R R
authors.initials: RR
authors.lastname: Tubbs
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002886:Chromosomes, Human, Pair 17; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D004273:DNA, Neoplasm / Q000032:analysis; D066246:ErbB Receptors / Q000235:genetics*; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D016591:Histocytological Preparation Techniques; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; D066246:ErbB Receptors; D017430:Prostate-Specific Antigen