Abstract
Abstract PBX1 has been initially identified as a proto-oncogene in human leukemia in a form of the E2A-PBX1 fusion protein. PBX1 is currently known as a regulator of self renewal of stem cells which contributes to maintenance of a “stemness” phenotype mainly through TGF-ß signaling. PBX1 was recently shown to be elevated in ovarian cancer and its locus was found to be frequently amplified in many cancer types including ovarian carcinoma. In order to further understand the clinicopathological and prognostic significance of PBX1 in ovarian carcinoma, we investigated the gene expression of PBX1 in patients with ovarian high-grade serous carcinoma (HGSC). PBX1 mRNA levels were analyzed in a panel of 78 ascites from patients with HGSC (including 36 primaries and 42 recurrences) by quantitative RT-PCR. Moreover, we performed immunohistochemical staining for PBX1 in 25 pairs of matched primary and recurrent HGSCs from the same patients. The results were correlated with clinicopathological data. Kaplan-Meier analysis demonstrated higher PBX1 levels in ascites from patients with recurrent/chemoresistant HGSC and an association with worse overall survival (p=0.026) as well as disease-free survival (p=0.024). Patients’ effusions with high PBX1 levels (based on median cut-off, n=22) had a mean overall survival of 26 months vs. 39 months for patients whose effusions showed low PBX1 expression (n=20). Patients’ effusions with high PBX1 expression (n=21) also had a mean progression-free survival of 4 months vs. 10 months for patients whose effusions showed low PBX1 levels (n=20). Furthermore, we found more intense PBX1 immunoreactivity in recurrent HGSCs than in matched primaries (Paired t test, p=0.024). Finally, PBX1 expression in primary HGSCs did not demonstrate any significant correlation with patients’ clinical outcome. This study is the first one demonstrating that PBX1 expression correlates with recurrent disease and is associated with worse clinical outcome in patients who develop recurrent HGSC. Future studies will aim at determining the usefulness of PBX1 immunoreactivity as a biomarker to predict patient treatment response and whether it can be a potential molecule for drug-targeted treatment in patients with recurrent HGSC. 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 LB-50.
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