Abstract 795: <i>SOX2: profiling a new group of breast cancer patients with poor prognosis</i>
Authors: Leon P. Pradel, Elisabeth Hinterseer, Stephan Bastelberger, Jane Beil, Roland Reitsamer, Otto Dietze, Cornelia Hauser-Kronberger
Journal: Cancer Research (2010)

Abstract SOX2 - the SRY (sex determining region Y)-box 2 transcription factor, as the key trigger in maintaining pluripotency in embryonic stem cells has shown to be up regulated in a variety of human breast cancers and especially in basal-like breast carcinomas. Aim of this morphologic study was to combine SOX2 immunohistochemical positive cases with their histopathological data to selected markers used already in daily diagnosis and combine those results to create a possible ‘SOX2 staining profile’ confirming poor prognosis within this group of patients. Poor prognosis in this context was defined on histopathological criteria as high grade/poorly differentiated invasive tumours with high stage and preferable basal-like phenotype with invasive lobular carcinomas possessing better prognosis instead of invasive ductal carcinomas. Also carcinomas with mesenchymal phenotype and high proliferation rate correlate with a much worse outcome. A collective of 20 invasive breast cancer patients selected from a 86 breast cancer cohort as well as 5 cases of non-malignant tissue from breast hypertrophy were immunohistochemically stained using formalin-fixed paraffin-embedded tissue samples and primary antibodies against SOX2 and 10 selected markers (β-catenin, CK5/6, Cyclin D1, EGFR, ER, Her2, Nanog, Oct-4, PR, Vimentin) known to be of prognostic values. 6 breast cancer cell lines (MCF-7, MDA-MB231, MDA-MB453, SK-BR3, SUM-159, T47-D) and 2 breast epithelial-like cell lines (MCF-10A, MCF-12A) provided as formalin-fixed paraffin-embedded cytoblocks were additionally analysed and characterized on a immunocytochemical level with identical markers. The markers used in this assay were beyond β-catenin as the activating partner of SOX2, Nanog and Oct-4 as important drivers of “stemness”, PR, ER and Her2 together with CK5/6 and EGFR to decrypt breast carcinomas with basal-like phenotype and finally Vimentin as a mesenchymal marker and CyclinD1 for illustrating cells into G1/S transition. During our investigations SOX2 revealed to be associated to patients with high grade (75%G3; 25%G2), stage (64,3% &amp;gt;T2) and in the majority of patients to a basal-like phenotype (42.3%). Interestingly SOX2 staining also referred strictly to invasive ductal carcinomas instead of invasive lobular carcinomas, mixed types or other tumoral subtypes. Within the SOX2 positive cases Vimentin and CK5/6 expression is correlated mainly to basal-like carcinomas demonstrating this tumor subclass is probably derived from a much more primitive, less differentiated progenitor or even stem-like pool of cells. Concerning the utilized breast cancer cell lines, these trends could also be verified on a cellular level. These findings suggest that SOX2 expression is generally linked to a subpopulation of breast cancer patients with poor prognosis. These results could be of potential value for further investigations concerning targeted therapy onset on SOX2 pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 795.