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

Hum Pathol. 2001 Dec;32(12):1392-7. doi: 10.1053/hupa.2001.29676.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Aged
  • Aged, 80 and over
  • Aneuploidy*
  • Chromosomes, Human, Pair 17*
  • Chromosomes, Human, Pair 7*
  • Chromosomes, Human, Pair 8*
  • DNA, Neoplasm / analysis
  • ErbB Receptors / genetics*
  • Gene Amplification
  • Genes, erbB-2 / genetics*
  • Histocytological Preparation Techniques
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prostate-Specific Antigen / analysis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery
  • Survival Rate
  • Treatment Outcome

Substances

  • DNA, Neoplasm
  • ErbB Receptors
  • Prostate-Specific Antigen