In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2273-2273
Abstract:
As member of the high-mobility-group (HMG)-domain containing proteins – SOX2 (Sex determining Region Y – box 2) transcriptional activator is known for its pivotal role in maintaining self-renewal, pluripotency and cellular identity in embryonic stem cells. While its status in adult tissue, e.g. in homeostasis – is still less understood and controversy – SOX2 has shown recently to be up regulated in a huge variety of human tumors like oesophagus, lung, brain and breast. Within this study whole sections – provided as formalin-fixed paraffin-embedded tumor samples, derived from 86 patients with advanced breast cancer disease were stained via immunohistochemistry (IHC) for SOX2 positivity. Further on – six breast cancer cell lines (MCF-7, MDA-MB231, MDA-MB453, SK-BR3, SUM-159, T47-D) as well as an individual based tissue micro array (TMA) containing 1080 fine needle biopsies were additionally analyzed using IHC and qRT-PCR. Initially – all samples have been evaluated for their particular molecular subtype (Luminal A, Luminal B, Normal-like, HER2 Overexpressing, Basal-like) and their histopathological parameters (histological subtype, grade, size, lymph node metastasis). For further proof of principle the applied SOX2 polyclonal antibody (SOX2 PAb AF2018, R & D SystemsTM) was validated for its marker capacity via Surface Plasmon Resonance (SPR) Spectroscopy and Western Blot to determine the kinetic profile, limit of detection, epitope variety and specificity of this antibody. With the so called ‘fishing’ opportunity for analyte recovery in SPR, native putative antigen bound by the SOX2 PAb can be enriched and further characterized from whole cell lysates. In conclusion – SOX2 showed association to overall bad prognosis due to high grade (p & lt;0.001), huge size (p=0.003), lymph node metastasis (p & lt;0.001) as well as histological and molecular subtypes with poor overall-survival (p & lt;0.001). Further on it is independent (p=0.6) of oestrogen receptor (ER) presence but correlated to EGFR expression (p=0.007). During antibody-based validation – SOX2 PAb revealed to possess high specificity, sensitivity and affinity to native and recombinant SOX2 full length protein finally. In this way SOX2 – as marker, can be applied to predict overall poor prognosis in breast cancer in an ER- and subtype-independent fashion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2273. doi:10.1158/1538-7445.AM2011-2273
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-2273
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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