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Histopathological characterization of ductal carcinoma in situ (DCIS) of the breast according to HER2 amplification status and molecular subtype

Mieke Van Bockstal (UGent) , Kathleen Lambein (UGent) , Hannelore Denys (UGent) , Geert Braems (UGent) , Ann Nuyts (UGent) , Rudy Van den Broecke (UGent) , Veronique Cocquyt (UGent) , Olivier De Wever (UGent) and Louis Libbrecht (UGent)
(2014) VIRCHOWS ARCHIV. 465(3). p.275-289
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Abstract
This study aimed to characterize ductal carcinoma in situ (DCIS) according to human epidermal growth factor receptor 2 (HER2) amplification status and molecular subtype. In addition, we performed a detailed HER2 and CEP17 copy number analysis and we assessed the impact of recent changes in the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on HER2 immunohistochemical (IHC) scores in DCIS. Nuclear grade, extensive comedonecrosis, stromal architecture, stromal inflammation, and progesterone receptor (PR) expression were significantly associated with HER2 amplification status. In multivariate analysis, stromal inflammation and extensive comedonecrosis were the only two features that remained significantly related to HER2 amplification status. The recent changes in ASCO/CAP guidelines resulted in significant upgrading of HER2 IHC score. Remarkably, about one in five non-amplified DCIS presented a 3+ IHC score, regardless of the scoring method. The biological significance of this phenomenon is presently unknown. After categorization according to molecular subtype, luminal A DCIS mainly presented histopathological features associated with good prognosis, whereas luminal B/HER2+ and HER2+ categories displayed a more aggressive phenotype. Overall, our results demonstrate that HER2-amplified DCIS constitute a clearly distinct subgroup which is characterized by histopathological features associated with poor prognosis. Further studies are required to elucidate the biological significance of a 3+ IHC score in non-amplified DCIS, as well as its mechanism.
Keywords
HER2 amplification, Copy number, Clusters, Ductal carcinoma in situ, Breast, PATHOLOGISTS GUIDELINE RECOMMENDATIONS, ESTROGEN-RECEPTOR STATUS, CLINICAL-ONCOLOGY/COLLEGE, AMERICAN-SOCIETY, PROGNOSTIC-SIGNIFICANCE, LOCAL RECURRENCE, CANCER CELLS, OVEREXPRESSION, PROGRESSION, EXPRESSION

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MLA
Van Bockstal, Mieke, Kathleen Lambein, Hannelore Denys, et al. “Histopathological Characterization of Ductal Carcinoma in Situ (DCIS) of the Breast According to HER2 Amplification Status and Molecular Subtype.” VIRCHOWS ARCHIV 465.3 (2014): 275–289. Print.
APA
Van Bockstal, M., Lambein, K., Denys, H., Braems, G., Nuyts, A., Van den Broecke, R., Cocquyt, V., et al. (2014). Histopathological characterization of ductal carcinoma in situ (DCIS) of the breast according to HER2 amplification status and molecular subtype. VIRCHOWS ARCHIV, 465(3), 275–289.
Chicago author-date
Van Bockstal, Mieke, Kathleen Lambein, Hannelore Denys, Geert Braems, Ann Nuyts, Rudy Van den Broecke, Veronique Cocquyt, Olivier De Wever, and Louis Libbrecht. 2014. “Histopathological Characterization of Ductal Carcinoma in Situ (DCIS) of the Breast According to HER2 Amplification Status and Molecular Subtype.” Virchows Archiv 465 (3): 275–289.
Chicago author-date (all authors)
Van Bockstal, Mieke, Kathleen Lambein, Hannelore Denys, Geert Braems, Ann Nuyts, Rudy Van den Broecke, Veronique Cocquyt, Olivier De Wever, and Louis Libbrecht. 2014. “Histopathological Characterization of Ductal Carcinoma in Situ (DCIS) of the Breast According to HER2 Amplification Status and Molecular Subtype.” Virchows Archiv 465 (3): 275–289.
Vancouver
1.
Van Bockstal M, Lambein K, Denys H, Braems G, Nuyts A, Van den Broecke R, et al. Histopathological characterization of ductal carcinoma in situ (DCIS) of the breast according to HER2 amplification status and molecular subtype. VIRCHOWS ARCHIV. 2014;465(3):275–89.
IEEE
[1]
M. Van Bockstal et al., “Histopathological characterization of ductal carcinoma in situ (DCIS) of the breast according to HER2 amplification status and molecular subtype,” VIRCHOWS ARCHIV, vol. 465, no. 3, pp. 275–289, 2014.
@article{5822146,
  abstract     = {This study aimed to characterize ductal carcinoma in situ (DCIS) according to human epidermal growth factor receptor 2 (HER2) amplification status and molecular subtype. In addition, we performed a detailed HER2 and CEP17 copy number analysis and we assessed the impact of recent changes in the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on HER2 immunohistochemical (IHC) scores in DCIS. Nuclear grade, extensive comedonecrosis, stromal architecture, stromal inflammation, and progesterone receptor (PR) expression were significantly associated with HER2 amplification status. In multivariate analysis, stromal inflammation and extensive comedonecrosis were the only two features that remained significantly related to HER2 amplification status. The recent changes in ASCO/CAP guidelines resulted in significant upgrading of HER2 IHC score. Remarkably, about one in five non-amplified DCIS presented a 3+ IHC score, regardless of the scoring method. The biological significance of this phenomenon is presently unknown. After categorization according to molecular subtype, luminal A DCIS mainly presented histopathological features associated with good prognosis, whereas luminal B/HER2+ and HER2+ categories displayed a more aggressive phenotype. Overall, our results demonstrate that HER2-amplified DCIS constitute a clearly distinct subgroup which is characterized by histopathological features associated with poor prognosis. Further studies are required to elucidate the biological significance of a 3+ IHC score in non-amplified DCIS, as well as its mechanism.},
  author       = {Van Bockstal, Mieke and Lambein, Kathleen and Denys, Hannelore and Braems, Geert and Nuyts, Ann and Van den Broecke, Rudy and Cocquyt, Veronique and De Wever, Olivier and Libbrecht, Louis},
  issn         = {0945-6317},
  journal      = {VIRCHOWS ARCHIV},
  keywords     = {HER2 amplification,Copy number,Clusters,Ductal carcinoma in situ,Breast,PATHOLOGISTS GUIDELINE RECOMMENDATIONS,ESTROGEN-RECEPTOR STATUS,CLINICAL-ONCOLOGY/COLLEGE,AMERICAN-SOCIETY,PROGNOSTIC-SIGNIFICANCE,LOCAL RECURRENCE,CANCER CELLS,OVEREXPRESSION,PROGRESSION,EXPRESSION},
  language     = {eng},
  number       = {3},
  pages        = {275--289},
  title        = {Histopathological characterization of ductal carcinoma in situ (DCIS) of the breast according to HER2 amplification status and molecular subtype},
  url          = {http://dx.doi.org/10.1007/s00428-014-1609-3},
  volume       = {465},
  year         = {2014},
}

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