Abstract

Abstract Ductal carcinoma in situ (DCIS) is the most common precancerous finding in mammography screens. DCIS generally has a good prognosis, and only 20-25% of the cases progress to invasive breast carcinoma (IBC) even if left untreated. Breast pathologists and radiologists have suggested that there are currently more than one kind of DCIS under the same diagnosis. A subset of DCIS cases with reduced survival rate are associated with casting-type calcifications that can be histologically detected within closely packed, contorted, newly formed ducts, a phenomenon called neoductgenesis. Tumors with neoductgenesis are often erroneously diagnosed as DCIS, while in fact, they are associated with higher degree of metastasis and should be considered invasive carcinomas. This tumor category currently lacks specific histopathological markers and the biological processes leading to metastasis via neoductgenesis remain poorly characterised. To reveal new information of this breast tumor type, we are currently conducting comprehensive characterization of FFPE tissue samples of DCIS cases with and without neoductgenesis using imaging mass cytometry analysis and immunohistochemistry of specific tumor areas. Preliminary results on immunofluorescence staining suggest that neoductgenesis is associated with changes in the expression of specific myoepithelial marker proteins compared to areas with pure DCIS. In addition, we are analysing the three-dimensional ductal architecture of these lesions. The information obtained from this study can lead to development of new diagnostic tools for the identification of early breast cancers with a higher risk of spreading. Early detection of these cases is important to ensure the effectiveness and timeliness of treatment, and at the same time to improve the patients' quality of life. Citation Format: Laura Lehtinen, Leena Koskinen, Markus Peurla, Emilia Huotari, Otto Kauko, Peter Dean, Pauliina Hartiala, Pia Boström, Emilia Peuhu. Molecular profiling of neoductgenesis in early stage breast cancer for the development of novel diagnostic biomarkers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A012.

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