P53 Alteration in Morphologically Normal/Benign Breast Tissue in Patients With Triple Negative High-grade Breast Carcinomas: Breast p53 Signature?

P53 alterations have been identified in approximately 23% of breast carcinomas, particularly in hormone receptors negative high-grade carcinomas. It is considered to be an early event in breast carcinogenesis. Nevertheless, the putative precursor lesion of high-grade breast carcinoma remains elusive. Breast excision specimens from 93 triple negative high-grade invasive ductal carcinomas, 48 ER +/PR +/Her2- non-high-grade invasive ductal carcinomas, and 50 mammoplasty breasts were selected. At least 2 tissue blocks with tumor and adjacent benign tissue were sectioned and subjected to immunohistochemistry (IHC) staining for p53. TP 53 gene sequencing was performed on select tumors. Further IHC staining for ER and Ki67 was performed on consecutive sections of tissue with p53-positive normal/benign cells. Fifty-one of the 93 (55%) high-grade carcinomas were positive for p53 alteration, while only 3 of the 48 (6.25%) non-high-grade carcinomas were p53 altered. Focal p53 positivity in adjacent normal/benign breast tissue was identified in 19 cases, with 18 of them also had p53 alteration in their carcinomas. Only one case had focal p53 staining in normal/benign tissue but the tumor was negative for p53 alteration. No p53 staining positivity was identified in the mammoplasty specimens. The p53-stained normal/benign cells were ER negative and did not show an increase in the Ki67 labeling index. These findings indicate that the p53 staining positivity in normal/benign breast tissue is not a random event. It could be considered as the “p53 signature” in breast and serve as an indicator for future potential risk of p53-positive high-grade breast carcinoma.