Abstract
Purpose
For invasive breast cancer (IBC), high SOX10 expression was reported particularly in TNBC. This raised the possibility that SOX10 may complement other breast markers for determining cancers of breast origin.
Methods
Here, we compared the expression of SOX10 with other breast markers (GATA3, mammaglobin and GCDFP15) and their combined expression in a large cohort of IBC together with nodal metastases. We have also evaluated the expression of GATA3 and SOX10 in a wide spectrum of non-breast carcinomas to assess their value as breast specific markers.
Results
Compared with other markers, SOX10 showed lower overall sensitivity (6.5%), but higher sensitivity in TNBC (31.4%) than other breast markers including GATA3 (29.7% for TNBC). Its expression demonstrated the highest concordance between the paired IBC and nodal metastases (96.4%, κ = 0.663) among all the breast markers. More importantly, SOX10 identified many GATA3-negative TNBC, thus the SOX10/GATA3 combination was the most sensitive marker combination for IBC (86.6%). For non-breast carcinoma, a high SOX10/GATA3 expression rate was found in melanoma (77.9%, predominately expressed SOX10), urothelial carcinoma (82.0%, predominately expressed GATA3) and salivary gland tumors (69.4%). Other carcinomas, including cancers from lungs, showed very low expression for the marker combination.
Conclusions
The data suggested that SOX10/GATA3 combination can be used for differentiating metastases of breast and multiple non-breast origins. However, the differentiation with melanoma and urothelial tumors required more careful histologic examination, thorough clinical information and additional site-specific IHC markers. For salivary gland tumors, the overlapping tumor types with IBC renders the differentiation difficult.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved, including dispensation from the requirement of patient consent by Joint Chinese University of Hong Kong—New Territories East Cluster clinical research ethics committee (2014.500).
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The samples involved in the current study were retrieved from pathology tissue bank after used for diagnosis. All samples were irreversibly anonymized prior to inclusion of the study. Researchers were blinded from patient data during experimental and statistical procedure. Patient confidentiality has been protected and the study involved minimal risk to the subjects, Therefore, the requirement to obtain written consent has been waived.
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Aphivatanasiri, C., Li, J., Chan, R. et al. Combined SOX10 GATA3 is most sensitive in detecting primary and metastatic breast cancers: a comparative study of breast markers in multiple tumors. Breast Cancer Res Treat 184, 11–21 (2020). https://doi.org/10.1007/s10549-020-05818-9
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DOI: https://doi.org/10.1007/s10549-020-05818-9