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p63 expression is associated with high histological grade, aberrant p53 expression and TP53 mutation in HER2-positive breast carcinoma
  1. Shuangping Guo1,2,
  2. Yingmei Wang1,
  3. Joseph Rohr3,
  4. Li Shang4,
  5. Jing Ma1
  1. 1Department of Pathology, The Basic Medicine Science and the First Affiliated Hospital of the Air Force Military Medical University, Xi'an, China
  2. 2State Key Laboratory of Oncobiology, Xi’an, China
  3. 3Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA
  4. 4Department of Vascular Intervention, the 9th Hospital of Xi’an, Xi’an, Shaan Xi, China
  1. Correspondence to Dr Shuangping Guo, Department of Pathology, the Basic Medicine Science and the First Affiliated Hospital of the Air Force Military Medical University, Xi'an, Shan Xi, China; guoshuangping3{at}163.com

Abstract

Aim p63, a member of the p53 family, is a myoepithelial cell marker usually expressed in metaplastic breast carcinoma and its expression suggests a myoepithelial phenotype. However, its expression and association with clinicopathological features of human epidermal growth factor receptor 2 (HER 2)-positive breast carcinoma is poorly investigated.

Materials and methods Sixty-seven patients with oestrogen receptor-negative and progesterone receptor-negative, HER2-positive breast carcinoma who received anti-HER2-based neoadjuvant±adjuvant therapy was retrospectively analysed.

Results Twenty cases were p63-positive and 47 cases were p63-negative. The clinicopathological features and tumour responses after neoadjuvant therapy and outcomes were analysed. Among HER2-positive tumours, expression of p63 was significantly associated with younger age (42.5 vs 55.9; p=0.010). Expression of p63 was also significantly associated with histological grade 3 (11/20 (55%) vs 11/47 (23.4%); p=0.012) and negatively associated with grade 2 (9/20 (45%) vs 36/47 (76.6%); p=0.012). Intriguingly, p63-positive breast carcinomas showed significant aberrant p53 expression by immunohistochemistry (16/18 (88.9%) vs 29/47 (61.7%); p=0.03) and of TP53 mutation by Sanger sequencing (15/16 (93.8%) vs 12/22 (54.5%); p=0.009). No significant difference in tumour response after anti-HER2 neoadjuvant therapy nor in survival were found between p63-positive and p63-negative breast carcinomas.

Conclusion Expression of p63 in HER2-positive breast carcinoma is significantly associated with younger age, poor differentiation, high histological grade and aberrant expression of p53 and of TP53 mutation. HER2-positive breast carcinoma with a myoepithelial immunophenotype shows distinctive clinicopathological features representing a distinct subtype of HER2-positive breast carcinoma. Further, these findings suggest an interaction between p63 and mutant p53 in the tumorigenesis of HER2-positive breast carcinomas.

  • breast diseases
  • pathology
  • molecular
  • breast neoplasms
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Footnotes

  • Handling editor Cheok Soon Lee.

  • Contributors SG conceived of the study, participated in its design, participated in the interpretation and analysis of data and drafted the manuscript. JR participated in design and drafted the manuscript. YW, LS and JM carried out the experiments and analysis of data. The authors read and approved the final manuscript.

  • Funding Chinese National Natural Science Foundation, No. 81772865.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval The study was conducted in accordance with institutional ethical regulations and patient consents were waived. This study was approved by the First Affinity Hospital of the Air Force Military Medical University review board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data generated or analyzed during this study are included in this article.

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