p53 alteration in morphologically normal/benign breast tissue in patients with triple-negative high-grade breast carcinomas: breast p53 signature?

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• 作者：Xi Wang ; MD^a ; ^{xi_wang@urmc.rochester.edu" class="auth_mail" title="E-mail the corresponding author} ; Moritz Stolla ; MD^a ; Brian Z. Ring ; PhD^b ; Qi Yang ; BS^a ; Todd S. Laughlin ; BS^a ; Paul G. Rothberg ; PhD^a ; Kristin Skinner ; MD^c ; David G. Hicks ; MD^a
• 关键词：p53 ; Benign breast tissue ; Triple-negative high-grade breast carcinoma ; Precursor of triple negative BC ; p53 signature
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：55
• 期：Complete
• 页码：196-201
• 全文大小：1116 K

文摘

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. m>TPm>53 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.