Abstract P1-07-08: TP53 alteration in morphologically benign breast tissue in patients with ER/PR negative high grade breast carcinomas: Marker for early detection of high risk patients for high grade carcinomas?
Authors: Wang Xi , Stolla Moritz , Laughlin Todd S , Rothberg Paul G , Skinner Kristin , Hicks David G 
Published: May 2015

Background: TP53 alterations have been identified in approximately 20% of breast carcinomas, especially in ER/PR negative high grade carcinomas. It is believed that TP53 alteration is an early event in the carcinogenesis of high grade breast carcinomas. TP53 alteration could even be identified in morphologically "benign" appearing breast tissues. Nevertheless, the precursor lesion of high grade ductal carcinoma in situ and/or invasive carcinoma is not well recognized morphologically.

Design: We retrospectively analyzed the TP53 status of 108 cases with high grade (modified Bloom-Richardson grade 3) invasive ductal carcinoma, 51 cases with non-high grade invasive ductal carcinoma, and 50 cases with benign breast from mammoplasty. The high grade carcinomas were all estrogen receptor (ER) and progesterone receptor (PR) negative and 96.3% of them were HER-2 negative. The non-high grade carcinomas were all ER and/or PR positive, 92.2% Her2 negative. Blocks with tumor and/or benign tissue were selected from each case. Immunohistochemical stain for p53 was performed. TP53 gene sequencing was performed on selected tumors with inconclusive p53 staining. Further ER and Ki67 immunohistochemical stains were performed on the blocks with p53 positive benign tissue.

Results: Of the 108 high grade carcinomas, 48 (44%) were positive for TP53 alteration. Seventeen of the 48 (35.4%) cases also showed focal p53 staining in the adjacent benign appearing tissue. Only one case was negative for TP53 alteration in tumor but with focal p53 staining in benign tissue. Of the non-high grade carcinomas, 5 (9.8%) were positive for TP53 alteration, one of which had focal p53 staining in adjacent benign breast tissue. No p53 staining positivity was identified in the mammoplasty specimens. The p53 staining positive benign glands were ER negative, and did not show an increase in Ki67 labeling index. The morphology of these cells appeared to be slightly enlarged nuclei, with a mildly increased nuclear/cytoplasm ratio, slightly irregular nuclear contours, open chromatin, and prominent nucleoli, but still within the limits of "benign" glands.

Conclusion:

TP53 is already altered in "benign" appearing breast glands in patients with high grade breast carcinomas. These glands show the same ER status as their counterpart carcinomas, but remain inactive with low Ki67 labeling index, indicating further genetic changes are needed to trigger the unlimited tumor growth and fully malignant transformation. The special morphology and p53 positivity of the "benign" appearing cells could serve as an indicator for future potential risk of TP53 positive high grade breast carcinoma.

Citation Format: Xi Wang, Moritz Stolla, Todd S Laughlin, Paul G Rothberg, Kristin Skinner, David G Hicks. TP53 alteration in morphologically benign breast tissue in patients with ER/PR negative high grade breast carcinomas: Marker for early detection of high risk patients for high grade carcinomas? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-08.