TY - JOUR
T1 - Aneusomy 17 in breast cancer
T2 - Its role in HER-2/neu protein expression and implication for clinical assessment of HER-2/neu status
AU - Wang, Sijian
AU - Saboorian, M. Hossein
AU - Frenkel, Eugene P.
AU - Haley, Barbara B.
AU - Siddiqui, Momin T.
AU - Gokaslan, Sefik
AU - Hynan, Linda
AU - Ashfaq, Raheela
N1 - Funding Information:
Copyright © 2002 by The United States and Canadian Academy of Pathology, Inc. VOL. 15, NO. 2, P. 137, 2002 Printed in the U.S.A. Date of acceptance: October 30, 2001. Research funding for statistical consulting was provided in part by the Simmons Cancer Center, The University of Texas Southwestern Medical Center. None of the authors had any financial or consultant relationship with any of the companies whose products were used in this study. No corporate funding was received for this study. Address reprint requests to: Raheela Ashfaq, M.D., Department of Pathology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9072; e-mail: ashfaq.raheela@pathology.swmed.edu; fax: 214-590-2721.
PY - 2002
Y1 - 2002
N2 - HER-2/neu protein overexpression in breast cancer is mostly caused by HER-2/neu gene amplification. However, it is unclear whether aneusomy 17 may also play a role. Using immunohistochemistry assay (IHC) with DAKO antibody and manual quantitation, 189 specimens were selected from archival invasive breast cancer specimens, including most IHC-positive and some IHC-negative cases (n = 158 and 31, respectively). They were then analyzed by PathVysion fluorescence in situ hybridization (FISH) assay (Vysis, Inc., Downers Grove, IL) and by an image analyzer (ACIS; ChromaVision Medical Systems, Inc., San Juan Capistrano, CA)-assisted IHC quantitation. Ninety-two cases contained disomy 17 (chromosome 17 centromere, 1.76-2.25 signals per cell) whereas 97 cases had aneusomy 17, including 82 with low polysomy (2.26-3.75 signals per cell), 10 with high polysomy (≥3.76 signals per cell), and 5 with hypodisomy (≤1.75 signals per cell). HER-2/neu protein expression had the highest correlation with HER-2/neu gene dosage (copy number; r =. 826), followed by the HER-2/neu gene to chromosome 17 ratio (r =. 733). The lowest correlation was with the chromosome 17 copy number (r =. 307), on which the 10 cases with high polysomy 17 had a disproportionately high impact. The FISH assay using the PathVysion criterion for HER-2/neu gene amplification (HER-2/neu gene to chromosome 17 ratio, ≥2.00) achieved higher concordance with ACIS IHC than did an alternative FISH criterion (absolute HER-2/neu gene copy number, ≥4.00 signals per cell). Most ACIS IHC-PathVysion FISH-discordant cases contained disomy or low polysomy 17, whereas all 10 cases with high polysomy 17 had no such discordance. However, two cases with monosomy 17 had ACIS IHC-PathVysion FISH discordance, i.e., with gene amplification, but no protein overexpression. Both cases would have had no gene amplification if the alternative FISH criterion had been used. In conclusion, aneusomy 17 is common in breast cancer. Except in a certain subset of cases, aneusomy 17 probably is not a significant factor for HER-2/neu protein expression or for clinical assessment of HER-2/neu status.
AB - HER-2/neu protein overexpression in breast cancer is mostly caused by HER-2/neu gene amplification. However, it is unclear whether aneusomy 17 may also play a role. Using immunohistochemistry assay (IHC) with DAKO antibody and manual quantitation, 189 specimens were selected from archival invasive breast cancer specimens, including most IHC-positive and some IHC-negative cases (n = 158 and 31, respectively). They were then analyzed by PathVysion fluorescence in situ hybridization (FISH) assay (Vysis, Inc., Downers Grove, IL) and by an image analyzer (ACIS; ChromaVision Medical Systems, Inc., San Juan Capistrano, CA)-assisted IHC quantitation. Ninety-two cases contained disomy 17 (chromosome 17 centromere, 1.76-2.25 signals per cell) whereas 97 cases had aneusomy 17, including 82 with low polysomy (2.26-3.75 signals per cell), 10 with high polysomy (≥3.76 signals per cell), and 5 with hypodisomy (≤1.75 signals per cell). HER-2/neu protein expression had the highest correlation with HER-2/neu gene dosage (copy number; r =. 826), followed by the HER-2/neu gene to chromosome 17 ratio (r =. 733). The lowest correlation was with the chromosome 17 copy number (r =. 307), on which the 10 cases with high polysomy 17 had a disproportionately high impact. The FISH assay using the PathVysion criterion for HER-2/neu gene amplification (HER-2/neu gene to chromosome 17 ratio, ≥2.00) achieved higher concordance with ACIS IHC than did an alternative FISH criterion (absolute HER-2/neu gene copy number, ≥4.00 signals per cell). Most ACIS IHC-PathVysion FISH-discordant cases contained disomy or low polysomy 17, whereas all 10 cases with high polysomy 17 had no such discordance. However, two cases with monosomy 17 had ACIS IHC-PathVysion FISH discordance, i.e., with gene amplification, but no protein overexpression. Both cases would have had no gene amplification if the alternative FISH criterion had been used. In conclusion, aneusomy 17 is common in breast cancer. Except in a certain subset of cases, aneusomy 17 probably is not a significant factor for HER-2/neu protein expression or for clinical assessment of HER-2/neu status.
KW - Aneusomy
KW - Breast cancer
KW - Fluorescence in situ hybridization
KW - HER-2/neu
KW - Image analysis
KW - Immunohistochemistry
KW - erbB-2
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U2 - 10.1038/modpathol.3880505
DO - 10.1038/modpathol.3880505
M3 - Article
C2 - 11850542
AN - SCOPUS:0036183416
SN - 0893-3952
VL - 15
SP - 137
EP - 145
JO - Modern Pathology
JF - Modern Pathology
IS - 2
ER -