PMID- 11693898
OWN - NLM
STAT- MEDLINE
DCOM- 20020211
LR  - 20071114
IS  - 1528-9117 (Print)
IS  - 1528-9117 (Linking)
VI  - 7
IP  - 5
DP  - 2001 Sep-Oct
TI  - Detection of low level HER-2/neu gene amplification in prostate cancer by 
      fluorescence in situ hybridization.
PG  - 395-403
AB  - PURPOSE: Although expression of the HER-2/neu oncogene has been correlated with 
      tumor progression in prostate cancer, the biologic significance of detecting 
      HER-2/neu gene amplification by fluorescence in situ hybridization (FISH) or 
      evidence for protein overexpression by immunohistochemistry (IHC) remains 
      unclear. In this study, we directly compared HER-2/neu FISH and IHC to determine 
      which may be more predictive of the response to trastuzumab. PATIENTS AND 
      METHODS: Forty patients with prostate cancer were analyzed for gene amplification 
      by FISH performed with HER-2/neu and chromosome 17 (CEP 17) DNA probes (Vysis). 
      Protein expression was examined by immunofluorescence and by IHC using the DAKO 
      HercepTest antibody protocol and a monoclonal antibody to Her-2/neu on archival 
      paraffin sections. The patients included 30 men with primary tumors that were 
      treated with radical prostatectomy. Of these, 15 demonstrated subsequent disease 
      progression within 3 years. Five patients with prostatic intraepithelial 
      neoplasia were tested, as were five with metastatic disease whose samples were 
      obtained before androgen ablation therapy. RESULTS: None of the 30 primary 
      prostate cancer specimens showed overexpression for HER-2/neu by 
      immunofluorescence or by IHC with the DAKO protocol. One sample showed 3+ 
      membrane expression with the monoclonal antibody. In contrast, low copy number 
      gene amplifications (3-8 HER-2/neu signals/nucleus) were detected in 16 of 30 
      samples (53%) by FISH. Most amplified cells were diploid for CEP 17, 
      demonstrating that amplification was not due to total cell aneuploidy. FISH and 
      IHC determined that prostatic intraepithelial neoplasia samples were normal. Four 
      of five (80%) metastatic samples were amplified for HER-2/neu by FISH. Nearly 70% 
      of metastatic cancer cells among all five specimens demonstrated aneuploidy. A 
      single lymph node metastasis showed 3+ membrane staining by IHC (DAKO). 
      CONCLUSIONS: In contrast to breast cancer, FISH detects HER-2/neu amplification 
      in a substantial proportion of prostate cancers that do not overexpress 
      HER-2/neuby IHC. Although the biologic significance of this finding is uncertain, 
      it has implications for the direction of current and planned clinical trials of 
      trastuzumab in advanced prostate cancer, including determination of patient 
      eligibility.
FAU - Liu, H L
AU  - Liu HL
AD  - Department of Internal Medicine, University of California, San Francisco, USA.
FAU - Gandour-Edwards, R
AU  - Gandour-Edwards R
FAU - Lara, P N Jr
AU  - Lara PN Jr
FAU - de Vere White, R
AU  - de Vere White R
FAU - LaSalle, J M
AU  - LaSalle JM
LA  - eng
GR  - CA62505/CA/NCI NIH HHS/United States
GR  - CA63265/CA/NCI NIH HHS/United States
GR  - R21CA78851-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer J
JT  - Cancer journal (Sudbury, Mass.)
JID - 100931981
SB  - IM
CIN - Cancer J. 2001 Sep-Oct;7(5):372-4. PMID: 11693894
MH  - Adenocarcinoma/*genetics
MH  - Aneuploidy
MH  - Gene Amplification
MH  - Genes, erbB-2/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Nucleic Acid Amplification Techniques
MH  - Prostatic Neoplasms/*genetics
EDAT- 2001/11/06 10:00
MHDA- 2002/02/12 10:01
CRDT- 2001/11/06 10:00
PHST- 2001/11/06 10:00 [pubmed]
PHST- 2002/02/12 10:01 [medline]
PHST- 2001/11/06 10:00 [entrez]
PST - ppublish
SO  - Cancer J. 2001 Sep-Oct;7(5):395-403.