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Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression

(2017) VIRCHOWS ARCHIV. 471(5). p.575-587
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Abstract
Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC. HER2 copy number-based amplification was present in 49% of pure DCIS, 16% of admixed DCIS, 18% of admixed IDC, and 8% of pure IDC. Amplified pure DCIS with clusters of HER2 signals showed a significantly lower HER2 copy number than amplified admixed DCIS with clusters. Whereas pure DCIS and admixed DCIS presented significant differences, the in situ and invasive component of admixed tumors showed striking similarities regarding mean HER2 and chromosome 17 centromere (CEP17) copy number, grade, and estrogen and progesterone receptor expression. The discrepant prevalence of HER2 amplification among breast cancer subgroups indirectly suggests that HER2 may not play a crucial role in the transition of in situ to invasive breast cancer. The similarities in HER2 amplification status between the in situ and invasive component of admixed tumors hint at a common biological pathway for both components. Our data support the theory that pure DCIS, pure IDC, and admixed lesions have a common progenitor, but can progress as separate lineages.
Keywords
Breast cancer progression, HER2 amplification, Clusters, HER2 protein overexpression, Ductal carcinoma in situ (DCIS), CARCINOMA-IN-SITU, PATHOLOGISTS GUIDELINE RECOMMENDATIONS, CLINICAL-ONCOLOGY-COLLEGE, AMERICAN-SOCIETY, LOCAL RECURRENCE, INVASIVE-CARCINOMA, PROGNOSTIC-FACTORS, MOLECULAR MARKERS, EXPRESSION, DCIS

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Citation

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MLA
Lambein, Kathleen, Mieke Van Bockstal, Lies Vandemaele, et al. “Comparison of HER2 Amplification Status Among Breast Cancer Subgroups Offers New Insights in Pathways of Breast Cancer Progression.” VIRCHOWS ARCHIV 471.5 (2017): 575–587. Print.
APA
Lambein, Kathleen, Van Bockstal, M., Vandemaele, L., Van den Broecke, R., Cocquyt, V., Geenen, S., Denys, H., et al. (2017). Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression. VIRCHOWS ARCHIV, 471(5), 575–587.
Chicago author-date
Lambein, Kathleen, Mieke Van Bockstal, Lies Vandemaele, Rudy Van den Broecke, Veronique Cocquyt, Sofie Geenen, Hannelore Denys, and Louis Libbrecht. 2017. “Comparison of HER2 Amplification Status Among Breast Cancer Subgroups Offers New Insights in Pathways of Breast Cancer Progression.” Virchows Archiv 471 (5): 575–587.
Chicago author-date (all authors)
Lambein, Kathleen, Mieke Van Bockstal, Lies Vandemaele, Rudy Van den Broecke, Veronique Cocquyt, Sofie Geenen, Hannelore Denys, and Louis Libbrecht. 2017. “Comparison of HER2 Amplification Status Among Breast Cancer Subgroups Offers New Insights in Pathways of Breast Cancer Progression.” Virchows Archiv 471 (5): 575–587.
Vancouver
1.
Lambein K, Van Bockstal M, Vandemaele L, Van den Broecke R, Cocquyt V, Geenen S, et al. Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression. VIRCHOWS ARCHIV. 2017;471(5):575–87.
IEEE
[1]
K. Lambein et al., “Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression,” VIRCHOWS ARCHIV, vol. 471, no. 5, pp. 575–587, 2017.
@article{8548861,
  abstract     = {Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC. HER2 copy number-based amplification was present in 49% of pure DCIS, 16% of admixed DCIS, 18% of admixed IDC, and 8% of pure IDC. Amplified pure DCIS with clusters of HER2 signals showed a significantly lower HER2 copy number than amplified admixed DCIS with clusters. Whereas pure DCIS and admixed DCIS presented significant differences, the in situ and invasive component of admixed tumors showed striking similarities regarding mean HER2 and chromosome 17 centromere (CEP17) copy number, grade, and estrogen and progesterone receptor expression. The discrepant prevalence of HER2 amplification among breast cancer subgroups indirectly suggests that HER2 may not play a crucial role in the transition of in situ to invasive breast cancer. The similarities in HER2 amplification status between the in situ and invasive component of admixed tumors hint at a common biological pathway for both components. Our data support the theory that pure DCIS, pure IDC, and admixed lesions have a common progenitor, but can progress as separate lineages.},
  author       = {Lambein, Kathleen and Van Bockstal, Mieke and Vandemaele, Lies and Van den Broecke, Rudy and Cocquyt, Veronique and Geenen, Sofie and Denys, Hannelore and Libbrecht, Louis},
  issn         = {0945-6317},
  journal      = {VIRCHOWS ARCHIV},
  keywords     = {Breast cancer progression,HER2 amplification,Clusters,HER2 protein overexpression,Ductal carcinoma in situ (DCIS),CARCINOMA-IN-SITU,PATHOLOGISTS GUIDELINE RECOMMENDATIONS,CLINICAL-ONCOLOGY-COLLEGE,AMERICAN-SOCIETY,LOCAL RECURRENCE,INVASIVE-CARCINOMA,PROGNOSTIC-FACTORS,MOLECULAR MARKERS,EXPRESSION,DCIS},
  language     = {eng},
  number       = {5},
  pages        = {575--587},
  title        = {Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression},
  url          = {http://dx.doi.org/10.1007/s00428-017-2161-8},
  volume       = {471},
  year         = {2017},
}

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