Abstract 5560: PROX1 expression and function in malignant gliomas

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL The PROX1 transcription factor, also known as Prospero in flies, plays a critical role in the development of various organs especially the lymphatic and central nervous systems. Mutations in Prospero induce brain tumor development in flies due to the lack of normal asymmetric neural stem cell division. Less is known about the expression and function of PROX1 in human brain tumors. First, we investigated expression of PROX1 using immunohistochemistry in 56 human astrocytic gliomas of different grades. PROX1 was found to be overexpressed in the majority of high grade tumors but not in grade I tumors or control tissue. Secondly, we addressed the prognostic value of PROX1 in a clinical cohort of patients with grade II gliomas (n=116). The number of PROX1 immunoreactive cells was used as a variable in survival analysis. Patients with tumors showing high PROX1 protein expression had poor outcome in the univariate analysis as well as in the multivariate analysis compared to those with low PROX1 expression. Thirdly, we found that PROX1 was expressed in glioma cell lines and we noted an apparent positive correlation between expression of PROX1 and the pluripotency factor SOX2. Depletion of SOX2 using siRNA inhibited glioma cell proliferation and reduced the levels of PROX1. Acute loss of PROX1 did not impair glioma cell proliferation in vitro. We conclude that PROX1 may constitute a useful tool for diagnosing and grading of astrocytic glioma distinguishing grade III and IV tumors from grade I and II tumors. PROX1 is also a novel predictor of survival for grade II gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5560. doi:1538-7445.AM2012-5560