HER-2 Testing in Breast Cancer Using Immunohistochemical Analysis and Fluorescence In Situ Hybridization: A Single-Institution Experience of 2,279 Cases and Comparison of Dual-Color and Single-Color Scoring

Priti Lal, Paulo A. Salazar, Clifford A. Hudis, Marc Ladanyi, Beiyun Chen

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122 Citations (Scopus)

Abstract

We analyzed concordance between immunohistochemical analysis and fluorescence in situ hybridization (FISH) in HER-2 status and studied the effect of dual-color (D-FISH) vs single-color FISH (S-FISH) scoring on the assignment of tumors to amplified or nonamplified categories. The assays were performed on formalin-fixed, paraffin-embedded sections of 2,279 invasive breast carcinomas. Immunohistochemical results were interpreted as negative (0, 1+) or positive (2+, 3+). For FISH analyses, a ratio for HER-2/chromosome 17 of 2.0 or more (D-FISH) or an absolute HER-2 copy number per nucleus of more than 4.0 (S-FISH) were interpreted as positive gene amplification. We found 547 (24.0%) cases positive immunohistochemically, 326 (14.3%) by D-FISH, and 351 (15.4%) by S-FISH. Overall concordance in HER-2 status with immunohistochemical analysis was 87% for D-FISH and 86% for S-FISH. Excellent concordance was found among groups scored immunohistochemically as 0, 1+, and 3+ (with D-FISH, 97%; with S-FISH, 96%). The most discordant category was the group scored 2+ immunohistochemically, in which only a quarter of the 2+ tumors were FISH(+). D-FISH and S-FISH scoring results were discordant in 89 tumors (4%), of which 8 (9%) had 3+ immunohistochemical staining and none showed high-level HER-2 amplification. Among all FISH(+) tumors, 10% were negative by immunohistochemical analysis, and notably almost half (47%) showed borderline to low HER-2 amplification (D-FISH score, 2.0-3.9); the clinical significance of these findings warrants further investigation.

Original languageEnglish (US)
Pages (from-to)631-636
Number of pages6
JournalAmerican Journal of Clinical Pathology
Volume121
Issue number5
DOIs
StatePublished - May 2004
Externally publishedYes

Fingerprint

Fluorescence In Situ Hybridization
Color
Breast Neoplasms
Neoplasms
Chromosomes, Human, Pair 17
Gene Amplification
Paraffin
Formaldehyde
Staining and Labeling

Keywords

  • Breast cancer
  • ERBB2
  • FISH
  • Fluorescence in situ hybridization
  • HER-2/neu
  • Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{5e3654e5bfd24208a485843e2ef57ec2,
title = "HER-2 Testing in Breast Cancer Using Immunohistochemical Analysis and Fluorescence In Situ Hybridization: A Single-Institution Experience of 2,279 Cases and Comparison of Dual-Color and Single-Color Scoring",
abstract = "We analyzed concordance between immunohistochemical analysis and fluorescence in situ hybridization (FISH) in HER-2 status and studied the effect of dual-color (D-FISH) vs single-color FISH (S-FISH) scoring on the assignment of tumors to amplified or nonamplified categories. The assays were performed on formalin-fixed, paraffin-embedded sections of 2,279 invasive breast carcinomas. Immunohistochemical results were interpreted as negative (0, 1+) or positive (2+, 3+). For FISH analyses, a ratio for HER-2/chromosome 17 of 2.0 or more (D-FISH) or an absolute HER-2 copy number per nucleus of more than 4.0 (S-FISH) were interpreted as positive gene amplification. We found 547 (24.0{\%}) cases positive immunohistochemically, 326 (14.3{\%}) by D-FISH, and 351 (15.4{\%}) by S-FISH. Overall concordance in HER-2 status with immunohistochemical analysis was 87{\%} for D-FISH and 86{\%} for S-FISH. Excellent concordance was found among groups scored immunohistochemically as 0, 1+, and 3+ (with D-FISH, 97{\%}; with S-FISH, 96{\%}). The most discordant category was the group scored 2+ immunohistochemically, in which only a quarter of the 2+ tumors were FISH(+). D-FISH and S-FISH scoring results were discordant in 89 tumors (4{\%}), of which 8 (9{\%}) had 3+ immunohistochemical staining and none showed high-level HER-2 amplification. Among all FISH(+) tumors, 10{\%} were negative by immunohistochemical analysis, and notably almost half (47{\%}) showed borderline to low HER-2 amplification (D-FISH score, 2.0-3.9); the clinical significance of these findings warrants further investigation.",
keywords = "Breast cancer, ERBB2, FISH, Fluorescence in situ hybridization, HER-2/neu, Immunohistochemistry",
author = "Priti Lal and Salazar, {Paulo A.} and Hudis, {Clifford A.} and Marc Ladanyi and Beiyun Chen",
year = "2004",
month = "5",
doi = "10.1309/VE78-62V2-646B-R6EX",
language = "English (US)",
volume = "121",
pages = "631--636",
journal = "American Journal of Clinical Pathology",
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publisher = "American Society of Clinical Pathologists",
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TY - JOUR

T1 - HER-2 Testing in Breast Cancer Using Immunohistochemical Analysis and Fluorescence In Situ Hybridization

T2 - A Single-Institution Experience of 2,279 Cases and Comparison of Dual-Color and Single-Color Scoring

AU - Lal, Priti

AU - Salazar, Paulo A.

AU - Hudis, Clifford A.

AU - Ladanyi, Marc

AU - Chen, Beiyun

PY - 2004/5

Y1 - 2004/5

N2 - We analyzed concordance between immunohistochemical analysis and fluorescence in situ hybridization (FISH) in HER-2 status and studied the effect of dual-color (D-FISH) vs single-color FISH (S-FISH) scoring on the assignment of tumors to amplified or nonamplified categories. The assays were performed on formalin-fixed, paraffin-embedded sections of 2,279 invasive breast carcinomas. Immunohistochemical results were interpreted as negative (0, 1+) or positive (2+, 3+). For FISH analyses, a ratio for HER-2/chromosome 17 of 2.0 or more (D-FISH) or an absolute HER-2 copy number per nucleus of more than 4.0 (S-FISH) were interpreted as positive gene amplification. We found 547 (24.0%) cases positive immunohistochemically, 326 (14.3%) by D-FISH, and 351 (15.4%) by S-FISH. Overall concordance in HER-2 status with immunohistochemical analysis was 87% for D-FISH and 86% for S-FISH. Excellent concordance was found among groups scored immunohistochemically as 0, 1+, and 3+ (with D-FISH, 97%; with S-FISH, 96%). The most discordant category was the group scored 2+ immunohistochemically, in which only a quarter of the 2+ tumors were FISH(+). D-FISH and S-FISH scoring results were discordant in 89 tumors (4%), of which 8 (9%) had 3+ immunohistochemical staining and none showed high-level HER-2 amplification. Among all FISH(+) tumors, 10% were negative by immunohistochemical analysis, and notably almost half (47%) showed borderline to low HER-2 amplification (D-FISH score, 2.0-3.9); the clinical significance of these findings warrants further investigation.

AB - We analyzed concordance between immunohistochemical analysis and fluorescence in situ hybridization (FISH) in HER-2 status and studied the effect of dual-color (D-FISH) vs single-color FISH (S-FISH) scoring on the assignment of tumors to amplified or nonamplified categories. The assays were performed on formalin-fixed, paraffin-embedded sections of 2,279 invasive breast carcinomas. Immunohistochemical results were interpreted as negative (0, 1+) or positive (2+, 3+). For FISH analyses, a ratio for HER-2/chromosome 17 of 2.0 or more (D-FISH) or an absolute HER-2 copy number per nucleus of more than 4.0 (S-FISH) were interpreted as positive gene amplification. We found 547 (24.0%) cases positive immunohistochemically, 326 (14.3%) by D-FISH, and 351 (15.4%) by S-FISH. Overall concordance in HER-2 status with immunohistochemical analysis was 87% for D-FISH and 86% for S-FISH. Excellent concordance was found among groups scored immunohistochemically as 0, 1+, and 3+ (with D-FISH, 97%; with S-FISH, 96%). The most discordant category was the group scored 2+ immunohistochemically, in which only a quarter of the 2+ tumors were FISH(+). D-FISH and S-FISH scoring results were discordant in 89 tumors (4%), of which 8 (9%) had 3+ immunohistochemical staining and none showed high-level HER-2 amplification. Among all FISH(+) tumors, 10% were negative by immunohistochemical analysis, and notably almost half (47%) showed borderline to low HER-2 amplification (D-FISH score, 2.0-3.9); the clinical significance of these findings warrants further investigation.

KW - Breast cancer

KW - ERBB2

KW - FISH

KW - Fluorescence in situ hybridization

KW - HER-2/neu

KW - Immunohistochemistry

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