TY - JOUR
T1 - Triple-negative and HER2 positive ductal carcinoma in situ of the breast
T2 - characteristics, behavior, and biomarker profile
AU - Takahashi, Satoshi
AU - Thike, Aye Aye
AU - Koh, Valerie Cui Yun
AU - Sasano, Hironobu
AU - Tan, Puay Hoon
N1 - Funding Information:
Funding This study was funded by the Health Services Research Competitive Research Grant, HSRG/0009/2010, from the Ministry of Health, Singapore.
Funding Information:
Satoshi Takahashi is a medical student intern on an elective posting from Tohoku University, Sendai, Japan. ST took part in the study design, analyzed the data, and wrote the manuscript. AAT took part in the study design, collected the clinicopathological data, evaluated the IHC stains, analyzed the data, and edited the manuscript. VCYK performed the experiments (tissue sectioning and IHC staining), assisted in data collection, and critically revised the manuscript. HS contributed substantially to the study design and critically reviewed and edited the manuscript. PHT conceived the study and critically reviewed and revised the manuscript. All authors gave final approval for publication. This is a retrospective study involving human FFPE tissues and has been approved by the SingHealth Centralised Institutional Review Board (CIRB) (Ref: 2010/610/F). This article does not contain any studies with animals performed by any of the authors. A waiver for informed consent was approved by the SingHealth CIRB. The authors declare that they no conflict of interest.
Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - We compared the characteristics, clinical behavior, and biomarker profile between HER2 positive (HER2+) and triple-negative (TN) ductal carcinoma in situ (DCIS) which are considered more aggressive than other DCIS subtypes. In addition, we explored the impact of these features on its potential of progression to invasive breast carcinomas. Cases of DCIS diagnosed at the Department of Pathology, Singapore General Hospital from 1994 to 2010 were identified. TN and HER2+ DCIS cases formed the study cohort. Immunohistochemistry (IHC) was performed for ER, PR, HER2, CK14, EGFR, and p53. Comparisons of clinicopathological features, IHC results, and clinical outcomes were performed between the two groups. We evaluated 145 HER2+ and 85 TN DCIS cases. HER2 positive DCIS had significantly higher nuclear grade (p < 0.001) and more frequent necrosis (p < 0.001) than TN DCIS. HER2 positive DCIS also harbored significantly higher rates of nuclear p53 immunoreactivity (p = 0.002) than TN DCIS. Younger patients (age < 40) with HER2+ and TN DCIS demonstrated statistically significant worse invasive DFS than older women (p < 0.001). Multivariate cox regression analysis (HR 15.08, 95% CI 12.79–81.45, p = 0.002) also confirmed these findings. In addition, younger patients (age < 40) with HER2+ DCIS experienced significantly poorer prognosis when p53 was also positive (p = 0.033). HER2+ DCIS had more aggressive pathological characteristics compared to TN DCIS; accumulation of mutant p53 could possibly be contributory. Age was an independent predictor of aggressive biological behavior of HER2+ and TN DCIS. We demonstrated that younger patients with p53 positive HER2+ DCIS had significantly adverse clinical outcome.
AB - We compared the characteristics, clinical behavior, and biomarker profile between HER2 positive (HER2+) and triple-negative (TN) ductal carcinoma in situ (DCIS) which are considered more aggressive than other DCIS subtypes. In addition, we explored the impact of these features on its potential of progression to invasive breast carcinomas. Cases of DCIS diagnosed at the Department of Pathology, Singapore General Hospital from 1994 to 2010 were identified. TN and HER2+ DCIS cases formed the study cohort. Immunohistochemistry (IHC) was performed for ER, PR, HER2, CK14, EGFR, and p53. Comparisons of clinicopathological features, IHC results, and clinical outcomes were performed between the two groups. We evaluated 145 HER2+ and 85 TN DCIS cases. HER2 positive DCIS had significantly higher nuclear grade (p < 0.001) and more frequent necrosis (p < 0.001) than TN DCIS. HER2 positive DCIS also harbored significantly higher rates of nuclear p53 immunoreactivity (p = 0.002) than TN DCIS. Younger patients (age < 40) with HER2+ and TN DCIS demonstrated statistically significant worse invasive DFS than older women (p < 0.001). Multivariate cox regression analysis (HR 15.08, 95% CI 12.79–81.45, p = 0.002) also confirmed these findings. In addition, younger patients (age < 40) with HER2+ DCIS experienced significantly poorer prognosis when p53 was also positive (p = 0.033). HER2+ DCIS had more aggressive pathological characteristics compared to TN DCIS; accumulation of mutant p53 could possibly be contributory. Age was an independent predictor of aggressive biological behavior of HER2+ and TN DCIS. We demonstrated that younger patients with p53 positive HER2+ DCIS had significantly adverse clinical outcome.
KW - Biomarkers
KW - Clinicopathological features
KW - DCIS
KW - HER2
KW - Recurrence
KW - Triple-negative
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U2 - 10.1007/s00428-018-2416-z
DO - 10.1007/s00428-018-2416-z
M3 - Article
C2 - 30033510
AN - SCOPUS:85050408801
VL - 473
SP - 275
EP - 283
JO - Virchows Archiv - Abteilung A Pathologische Anatomie
JF - Virchows Archiv - Abteilung A Pathologische Anatomie
SN - 0945-6317
IS - 3
ER -