TP53 mutations in ductal carcinoma in situ of the breast are associated with ipsilateral invasive recurrence
(2025) 15th Joint Meeting of the BDIAP and the Pathological Society — Location: (Belgium) Ghent (24.June.2025)
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- PURPOSE OF THE STUDY: Ductal carcinoma in situ (DCIS) of the breast is regarded as a non-obligate precursor of invasive breast cancer. The natural behaviour of DCIS is unknown, since most patients undergo surgery after a DCIS diagnosis. This study aimed to identify biomarkers for the prediction of ipsilateral invasive recurrence after surgery, by comparing the features of DCIS with an in situ recurrence versus DCIS with an invasive recurrence. METHODS: Representative tissue blocks from primary DCIS and their ipsilateral recurrence were retrieved. Brightfield immunohistochemistry (IHC) was performed for oestrogen receptor (ER), progesterone receptor (PR) and HER2. Immunofluorescence multiplex IHC was performed for EGFR, p53, decorin, versican, CD3 and CD20. All IHC stains were performed using an automated slides stainer. All DCIS were subjected to next-generation sequencing (NGS) to determine TP53 status. Statistics comprised univariate Cox survival analyses. SUMMARY OF RESULTS: In total, 44 DCIS patients with an ipsilateral recurrence after surgery were identified: 23 in situ recurrences and 21 invasive recurrences. Stromal expression of decorin and versican and stromal tumour-infiltrating lymphocytes were not associated with the time to invasive recurrence. Expression of ER, PR, HER2 and EGFR in the neoplastic cells were not predictive for invasive recurrence. TP53-mutated DCIS showed a significantly shorter mean time to ipsilateral invasive recurrence (26 months) than DCIS without TP53 mutations (89 months; p = 0.016; hazard ratio 3.537; 95% confidence interval 1.267–9.869). These NGS-based findings were confirmed by the p53 IHC staining pattern. CONCLUSIONS: TP53 mutation status is a promising predictive marker to identify DCIS patients at high risk of developing ipsilateral invasive recurrence, and p53 IHC can be used as a surrogate marker. This observation requires validation in larger, independent patient cohorts.
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Riggi, J., Spans, L., Vander Borght, S., Benhaddi, N., Bouzin, C., Daumerie, C., Libbrecht, L., Alaerts, H., Vercruysse, P., Staelens, G., Berlière, M., Galant, C., Vanden Bempt, I., & Van Bockstal, M. (2025). TP53 mutations in ductal carcinoma in situ of the breast are associated with ipsilateral invasive recurrence. Journal of Pathology, 267(Suppl 2), S6. https://hdl.handle.net/2078.5/277256 (Original work published 2025)