Abstract P2-06-05: Expression of the pluripotency transcription factor SOX2 in primary breast cancers (BCs): Correlation with clinicopathological features (CPfs) and recurrence
Authors: Barbara Pistilli, Giovanni Benedetti, Mauro Finicelli, Tiziana Squillaro, Andrea Marcellusi, Tommasina Biscotti, Alfredo Santinelli, Paola Mariani, Paolo Decembrini, Giancarlo Ciccioli, Luciano Latini, Antonio Giordano, Umberto Galderisi
Journal: Cancer Research (2015)

Abstract BACKGROUND SOX2 is one of the pluripotency transcription factors expressed by stem cells, which plays a central role in controlling the expression of genes implicated in embryonic development and stemness manteinance. Key regulators of embryonic stem cell (ESC) identity, such as NANOG, SOX2, OCT4 and GDF3 resulted overexpressed in a variety of solid tumors with a possible role in cancer progression and prognosis. SOX2 expression has mainly been reported in basal-like BC subtype, suggesting a role in conferring a less differentiated phenotype. In our analysis we evaluated a heterogenous group of BC tissues to determine whether the expression of ESC-regulating genes correlated with CPfs and recurrence. METHODS 140 primary invasive BC specimens were collected from 137 female patients who underwent surgery. mRNA expression for SOX2, OCT4, NANOG, GDF3 genes was assessed by RT-PCR. Immunoistochemistry (IHC) was performed for SOX2 with mouse monoclonal antibody (1:50, Y17, Santa Cruz Biotechnology, USA). Correlations with molecular subtypes, menopausal status, grading, ER, PR, ki67 (≤ 20% and &amp;gt; 20%), HER2, T-size and node status were evaluated by Fisher's exact test and χ2 test. Association of ESC-genes, CPfs and DFS was estimated by univariate and multivariate Cox-regression analysis (p≤ 0.05). Survival analysis (DFS and OS) were calculated by Kaplan-Meier curves and compared by log-rank test. RESULTS In 117 samples assessable by RT-PCR the genes resulted expressed as follows: NANOG=52 (44.5%), SOX2=11 (9.4%), GDF3=9 (7.2%), OCT-4=0. Correlation of mRNA gene expression with CPfs was statistically significant between NANOG and grade 2, GDF3 and node-negative status, SOX2 and higher ki67 (p=0.019, p=0.029, p= 0.035, respectively). Six out of 11 SOX2+ tumors were HER2+ (data not statistically significant); in the remaining 5 samples the fluorescence in situ hybridization was performed but no HER2 amplification was detected. At univariate analysis of DFS, SOX2 expression (HR=2,36; p=0.002), ki67 (HR= 2,19; p=0,028), T-size &amp;gt;1 (HR=2,06; p=2.011), node-status (HR=2,21; p= 0.014); ER/PR(HR=0,58/HR=0,59, p=0.065/p=0.068) resulted statistically significant. At multivariate analysis, SOX2 (HR=2,99; 95% CI 1,41-6,30; p=0.004), node-status (HR=2,44; 95%CI 1,25-4,76; p=0.009) and T-size &amp;gt;1 (HR=1,77; 95% CI=0,99-3,13; p=0.051) were independently associated with increased risk of recurrence. An earlier recurrence was observed in SOX2+ patients (median 34.9 months; 95% CI: 7.5-62.2) than SOX2- patients (median: 60.3 months; 95% CI: 32.6-88.1) (p=0.017); OS resulted shorter in SOX2+ (68.2 months 95%CI: 63.7-151.4 vs 145.3 months 95% CI: 80.5-210.2) albeit not statistically significant (p=0.104). IHC analysis showed a positive score for SOX2 protein expression in all of 11 samples with SOX2 mRNA amplification; SOX2+ protein was not detected in 20 samples randomly selected among the tissues not expressing SOX2 mRNA. CONCLUSIONS Our analysis confirm that ESC-regulating genes correlate with specific CPfs (grading, node-status and ki67). Notably, SOX2 resulted to be an independent prognostic factor, as it was associated with a risk of recurrence increased by 3 times, irrespective of other CPfs. Citation Format: Barbara Pistilli, Giovanni Benedetti, Mauro Finicelli, Tiziana Squillaro, Andrea Marcellusi, Tommasina Biscotti, Alfredo Santinelli, Paola Mariani, Paolo Decembrini, Giancarlo Ciccioli, Luciano Latini, Antonio Giordano, Umberto Galderisi. Expression of the pluripotency transcription factor SOX2 in primary breast cancers (BCs): Correlation with clinicopathological features (CPfs) and recurrence [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-05.