Department of Pathology, The Basic Medicine Science and the First Affiliated Hospital of the Air Force Military Medical University, Xi'an, China
State Key Laboratory of Oncobiology, Xi'an, China.
J Clin Pathol. 2021 Oct;74(10):641-645. doi: 10.1136/jclinpath-2020-206643. Epub 2020 Sep 1.
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.
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.
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 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.
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 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.
p63 是 p53 家族的一员，是一种肌上皮细胞标志物，通常在化生型乳腺癌中表达，其表达提示肌上皮表型。然而，其在人表皮生长因子受体 2（HER2）阳性乳腺癌中的表达及其与临床病理特征的关系尚未得到充分研究。
回顾性分析了 67 例雌激素受体阴性和孕激素受体阴性、HER2 阳性乳腺癌患者，这些患者接受了基于抗 HER2 的新辅助±辅助治疗。
20 例为 p63 阳性，47 例为 p63 阴性。分析了新辅助治疗后的临床病理特征和肿瘤反应以及治疗结果。在 HER2 阳性肿瘤中，p63 的表达与年龄较小显著相关（42.5 岁比 55.9 岁；p=0.010）。p63 的表达也与组织学 3 级显著相关（11/20（55%）比 11/47（23.4%）；p=0.012），与 2 级呈负相关（9/20（45%）比 36/47（76.6%）；p=0.012）。有趣的是，免疫组织化学检测到 p63 阳性乳腺癌中 p53 的表达显著异常（16/18（88.9%）比 29/47（61.7%）；p=0.03），Sanger 测序检测到 突变（15/16（93.8%）比 12/22（54.5%）；p=0.009）。p63 阳性和 p63 阴性乳腺癌患者在抗 HER2 新辅助治疗后的肿瘤反应和生存方面无显著差异。
在 HER2 阳性乳腺癌中，p63 的表达与年龄较小、分化差、组织学分级高、p53 表达异常及 突变显著相关。具有肌上皮免疫表型的 HER2 阳性乳腺癌具有独特的临床病理特征，代表了一种独特的 HER2 阳性乳腺癌亚型。此外，这些发现提示 p63 和突变型 p53 之间在 HER2 阳性乳腺癌的发生中存在相互作用。
