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Co-expression of p16 and p53 characterizes aggressive subtypes of ductal intraepithelial neoplasia

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Abstract

In the USA alone, approximately 61,000 new diagnoses of ductal intraepithelial neoplasia 1c-3 (DIN) are made each year. Around 10–20 % of the patients develop a recurrence, about 50 % of which are invasive. Prior studies have shown that invasive breast carcinomas positive for p16 or p53 have a higher frequency of recurrence and a more aggressive course; however, the co-expression of these markers across the entire spectrum of DIN and its potential correlation with grade of the lesions has not been studied previously. Immunohistochemical staining for p16 and p53 was evaluated on 262 DIN lesions from 211 cases diagnosed between 1991 and 2008. The lesions ranged from DIN1b (atypical intraductal hyperplasia) to DIN3 (DCIS, grade 3) and included 45 cases with associated invasive carcinoma. Frequency of staining for both p16 and p53 increased with increasing grade of DIN. Strong co-expression was found exclusively in higher grade DIN lesions (DIN2 and DIN3) particularly those associated with periductal stromal fibrosis and lymphocytic infiltrate. Strong co-expression was seen in 8 of 12 DIN3 lesions (67 %) associated with invasive carcinoma. In conclusion, co-expression of p16 and p53 increases with advancing grade of DIN and is maximal in high grade DIN lesions associated with invasive carcinoma, indicating a more aggressive phenotype. A distinctive variant of DIN with periductal fibrosis and lymphocytic infiltrate invariably falls into the high-grade category, based on either morphology or marker expression. Co-expression of p16/p53 may be of help in distinguishing between high-grade and low-grade DIN lesions.

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Author notes

  1. Jee-Yeon Kim

    Present address: Department of Pathology, School of Medicine, Pusan National University, Busan, South Korea

  2. Trine Tramm

    Present address: Department of Pathology, Aarhus University Hospital, Nørrebrogade 44, Building 18, 8000, Aarhus C, Denmark

Authors and Affiliations

  1. Department of Pathology, School of Medicine, Yale University, New Haven, CT, USA

    Charles Bechert, Jee-Yeon Kim, Trine Tramm & Fattaneh A. Tavassoli

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  1. Charles Bechert
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Correspondence to Trine Tramm.

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Conflict of interest

Trine Tramm holds a patent for a gene signature associated with efficacy of postmastectomy radiotherapy in invasive breast cancer (international patent publication no. WO 2013/132354 A2). The patent is not related to the present work. The authors have no other conflict of interests to declare.

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The study was approved by the Institutional Human Investigation Committee at Yale New Haven Hospital.

Funding

The work was supported by Fattaneh Tavassoli’s departmental start-up funds.

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Authors’ contributions

C. Bechert and F.T. Tavassoli conceptualized and designed the study. C. Bechert, J-Y. Kim, and F.T. Tavassoli acquired data. C. Bechert and T. Tramm analyzed and interpreted data (e.g., statistical analysis, biostatistics, computational analysis). C. Bechert, J-Y. Kim, T. Tramm, and F.T. Tavassoli drafted and revised the manuscript.

The work was carried out at the Department of Pathology, Yale University, School of Medicine, New Haven, USA.

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Bechert, C., Kim, JY., Tramm, T. et al. Co-expression of p16 and p53 characterizes aggressive subtypes of ductal intraepithelial neoplasia. Virchows Arch 469, 659–667 (2016). https://doi.org/10.1007/s00428-016-2024-8

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  • DOI: https://doi.org/10.1007/s00428-016-2024-8

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