title: p53 alteration in morphologically normal/benign breast tissue in patients with triple-negative high-grade breast carcinomas: breast p53 signature?
abstract: p53 alterations have been identified in approximately 23% of breast carcinomas, particularly in hormone receptor-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 estrogen receptor (ER)-positive/progesterone receptor-positive/Her2-negative 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 staining for p53. TP53 gene sequencing was performed on select tumors. Further immunohistochemistry staining for ER and Ki-67 was performed on consecutive sections of tissue with p53-positive normal/benign cells. Of the 93 high-grade carcinomas, 51 (55%) were positive for p53 alteration, whereas only 3 (6.25%) of the 48 non-high-grade carcinomas were p53 altered. Focal p53 positivity in adjacent normal/benign breast tissue was identified in 19 cases, and 18 of them also had p53 alteration in their carcinomas. Only 1 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 Ki-67 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.
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642. Electronic address: xi_wang@urmc.rochester.edu.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Moritz
authors.initials: M
authors.lastname: Stolla
authors.affiliation: College of Life Science, Institute of Personalized and Genomic Medicine, Huazhong University of Science and Technology, Wuhan, China 430074.
authors.forename: Brian Z
authors.initials: BZ
authors.lastname: Ring
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Todd S
authors.initials: TS
authors.lastname: Laughlin
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Rothberg
authors.affiliation: Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: Kristin
authors.initials: K
authors.lastname: Skinner
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642.
authors.forename: David G
authors.initials: DG
authors.lastname: Hicks
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D009154:Mutation; D060787:Neoplasm Grading; D010641:Phenotype; D011960:Receptors, Estrogen / Q000032:analysis; D059467:Transcriptome; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Benign breast tissue; Precursor of triple negative BC; Triple-negative high-grade breast carcinoma; p53; p53 signature