Detection of low level HER-2/neu gene amplification in prostate cancer by fluorescence in situ hybridization

Howard L. Liu, Regina Gandour-Edward, Primo N Lara, Ralph W deVere White, Janine M LaSalle

Research output: Contribution to journalArticle

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Abstract

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 fluo-rescence in situ hybridization (FISH) or evidence for protein over-expression 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/neu by 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.

Original languageEnglish (US)
Pages (from-to)395-403
Number of pages9
JournalCancer Journal
Volume7
Issue number5
StatePublished - Sep 2001

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erbB-2 Genes
Gene Amplification
Fluorescence In Situ Hybridization
In Situ Hybridization
Prostatic Neoplasms
Immunohistochemistry
Prostatic Intraepithelial Neoplasia
Aneuploidy
Fluorescent Antibody Technique
Eligibility Determination
Monoclonal Antibodies
Neoplasms
Chromosomes, Human, Pair 17
Membranes
DNA Probes
Prostatectomy
Diploidy
Oncogenes
Paraffin
Androgens

Keywords

  • FISH
  • HER-2/neu
  • Immunohistochemistry
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Detection of low level HER-2/neu gene amplification in prostate cancer by fluorescence in situ hybridization. / Liu, Howard L.; Gandour-Edward, Regina; Lara, Primo N; deVere White, Ralph W; LaSalle, Janine M.

In: Cancer Journal, Vol. 7, No. 5, 09.2001, p. 395-403.

Research output: Contribution to journalArticle

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abstract = "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 fluo-rescence in situ hybridization (FISH) or evidence for protein over-expression 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/neu by 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.",
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T1 - Detection of low level HER-2/neu gene amplification in prostate cancer by fluorescence in situ hybridization

AU - Liu, Howard L.

AU - Gandour-Edward, Regina

AU - Lara, Primo N

AU - deVere White, Ralph W

AU - LaSalle, Janine M

PY - 2001/9

Y1 - 2001/9

N2 - 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 fluo-rescence in situ hybridization (FISH) or evidence for protein over-expression 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/neu by 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.

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 fluo-rescence in situ hybridization (FISH) or evidence for protein over-expression 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/neu by 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.

KW - FISH

KW - HER-2/neu

KW - Immunohistochemistry

KW - Prostate cancer

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