HER2 testing in patients with breast cancer: Poor correlation between weak positivity by immunohistochemistry and gene amplification by fluorescence in situ hybridization

Edith A. Perez, Patrick C. Roche, Robert Brian Jenkins, Carol A. Reynolds, Kevin C. Halling, James N. Ingle, Lester E. Wold

Research output: Contribution to journalArticle

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Abstract

Objective: To evaluate amplification of the HER-2/neu gene by fluorescence in situ hybridization (FISH) in tumors with weakly positive (2+) immunohistochemical staining. Methods: A total of 1556 breast tumor biopsy specimens were referred to Mayo Medical Laboratories, Rochester, Minn, for HER2 testing between August and December 2000. Immunohistochemical (IHC) analysis was performed with use of a diagnostic test for the assessment of HER2 overexpression, the HercepTest. The IHC-stained slides were interpreted and scored on a scale ranging from 0 to 3+ according to Food and Drug Administration-approved guidelines. All specimens scored as 2+ were also routinely evaluated by FISH with use of a HER-2/neu DNA probe kit (PathVysion). Specimens were determined to be amplified if the ratio of HER-2/neu signals to chromosome 17 centromere (CEP17) signals was higher than 2.0. Results: Thirty-eight percent of the specimens evaluated with the HercepTest were scored 0, 35% were 1+, 14% were 2+, and 13% were 3+. Of the 216 tumor specimens scored as 2+, 26 (12%) had a high level of HER-2/neu gene amplification, 54 (25%) demonstrated duplication of HER2, 4 (2%) deleted HER-2/neu and/or CEP17, and 123 (57%) had no apparent HER-2/neu anomaly, no apparent CEP17 anomaly, nor apparent single gain (aneusomy) of CEP17. Conclusion: We recommend that all specimens with a 2+ HercepTest result be evaluated by FISH for HER-2/neu gene amplification. The results of both assays should be considered before making a decision to recommend anti-HER2 therapy.

Original languageEnglish (US)
Pages (from-to)148-154
Number of pages7
JournalMayo Clinic Proceedings
Volume77
Issue number2
StatePublished - 2002

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erbB-2 Genes
Gene Amplification
Fluorescence In Situ Hybridization
Immunohistochemistry
Breast Neoplasms
Chromosomes, Human, Pair 17
Centromere
DNA Probes
United States Food and Drug Administration
Routine Diagnostic Tests
Neoplasms
Decision Making
Guidelines
Staining and Labeling
Biopsy

ASJC Scopus subject areas

  • Medicine(all)

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HER2 testing in patients with breast cancer : Poor correlation between weak positivity by immunohistochemistry and gene amplification by fluorescence in situ hybridization. / Perez, Edith A.; Roche, Patrick C.; Jenkins, Robert Brian; Reynolds, Carol A.; Halling, Kevin C.; Ingle, James N.; Wold, Lester E.

In: Mayo Clinic Proceedings, Vol. 77, No. 2, 2002, p. 148-154.

Research output: Contribution to journalArticle

Perez, Edith A. ; Roche, Patrick C. ; Jenkins, Robert Brian ; Reynolds, Carol A. ; Halling, Kevin C. ; Ingle, James N. ; Wold, Lester E. / HER2 testing in patients with breast cancer : Poor correlation between weak positivity by immunohistochemistry and gene amplification by fluorescence in situ hybridization. In: Mayo Clinic Proceedings. 2002 ; Vol. 77, No. 2. pp. 148-154.
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abstract = "Objective: To evaluate amplification of the HER-2/neu gene by fluorescence in situ hybridization (FISH) in tumors with weakly positive (2+) immunohistochemical staining. Methods: A total of 1556 breast tumor biopsy specimens were referred to Mayo Medical Laboratories, Rochester, Minn, for HER2 testing between August and December 2000. Immunohistochemical (IHC) analysis was performed with use of a diagnostic test for the assessment of HER2 overexpression, the HercepTest. The IHC-stained slides were interpreted and scored on a scale ranging from 0 to 3+ according to Food and Drug Administration-approved guidelines. All specimens scored as 2+ were also routinely evaluated by FISH with use of a HER-2/neu DNA probe kit (PathVysion). Specimens were determined to be amplified if the ratio of HER-2/neu signals to chromosome 17 centromere (CEP17) signals was higher than 2.0. Results: Thirty-eight percent of the specimens evaluated with the HercepTest were scored 0, 35{\%} were 1+, 14{\%} were 2+, and 13{\%} were 3+. Of the 216 tumor specimens scored as 2+, 26 (12{\%}) had a high level of HER-2/neu gene amplification, 54 (25{\%}) demonstrated duplication of HER2, 4 (2{\%}) deleted HER-2/neu and/or CEP17, and 123 (57{\%}) had no apparent HER-2/neu anomaly, no apparent CEP17 anomaly, nor apparent single gain (aneusomy) of CEP17. Conclusion: We recommend that all specimens with a 2+ HercepTest result be evaluated by FISH for HER-2/neu gene amplification. The results of both assays should be considered before making a decision to recommend anti-HER2 therapy.",
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N2 - Objective: To evaluate amplification of the HER-2/neu gene by fluorescence in situ hybridization (FISH) in tumors with weakly positive (2+) immunohistochemical staining. Methods: A total of 1556 breast tumor biopsy specimens were referred to Mayo Medical Laboratories, Rochester, Minn, for HER2 testing between August and December 2000. Immunohistochemical (IHC) analysis was performed with use of a diagnostic test for the assessment of HER2 overexpression, the HercepTest. The IHC-stained slides were interpreted and scored on a scale ranging from 0 to 3+ according to Food and Drug Administration-approved guidelines. All specimens scored as 2+ were also routinely evaluated by FISH with use of a HER-2/neu DNA probe kit (PathVysion). Specimens were determined to be amplified if the ratio of HER-2/neu signals to chromosome 17 centromere (CEP17) signals was higher than 2.0. Results: Thirty-eight percent of the specimens evaluated with the HercepTest were scored 0, 35% were 1+, 14% were 2+, and 13% were 3+. Of the 216 tumor specimens scored as 2+, 26 (12%) had a high level of HER-2/neu gene amplification, 54 (25%) demonstrated duplication of HER2, 4 (2%) deleted HER-2/neu and/or CEP17, and 123 (57%) had no apparent HER-2/neu anomaly, no apparent CEP17 anomaly, nor apparent single gain (aneusomy) of CEP17. Conclusion: We recommend that all specimens with a 2+ HercepTest result be evaluated by FISH for HER-2/neu gene amplification. The results of both assays should be considered before making a decision to recommend anti-HER2 therapy.

AB - Objective: To evaluate amplification of the HER-2/neu gene by fluorescence in situ hybridization (FISH) in tumors with weakly positive (2+) immunohistochemical staining. Methods: A total of 1556 breast tumor biopsy specimens were referred to Mayo Medical Laboratories, Rochester, Minn, for HER2 testing between August and December 2000. Immunohistochemical (IHC) analysis was performed with use of a diagnostic test for the assessment of HER2 overexpression, the HercepTest. The IHC-stained slides were interpreted and scored on a scale ranging from 0 to 3+ according to Food and Drug Administration-approved guidelines. All specimens scored as 2+ were also routinely evaluated by FISH with use of a HER-2/neu DNA probe kit (PathVysion). Specimens were determined to be amplified if the ratio of HER-2/neu signals to chromosome 17 centromere (CEP17) signals was higher than 2.0. Results: Thirty-eight percent of the specimens evaluated with the HercepTest were scored 0, 35% were 1+, 14% were 2+, and 13% were 3+. Of the 216 tumor specimens scored as 2+, 26 (12%) had a high level of HER-2/neu gene amplification, 54 (25%) demonstrated duplication of HER2, 4 (2%) deleted HER-2/neu and/or CEP17, and 123 (57%) had no apparent HER-2/neu anomaly, no apparent CEP17 anomaly, nor apparent single gain (aneusomy) of CEP17. Conclusion: We recommend that all specimens with a 2+ HercepTest result be evaluated by FISH for HER-2/neu gene amplification. The results of both assays should be considered before making a decision to recommend anti-HER2 therapy.

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