Tamador Elsir, Mingqi Qu, Dan Ribom, Anja Smits, Monica Nistér, A. von Deimling, Shala Ghaderi Berntsson, Tommie Olofsson, Abiel Orrego, Christian Hartmann, and Mikael S. Lindström
Adult low-grade gliomas (LGG) are poorly circumscribed diffusely infiltrative brain tumours localised mainly in the cerebral hemispheres. They affect otherwise healthy individuals with an average age of ∼40 years at the time of diagnosis. Low-grade gliomas in adults are classified as grade II gliomas according to the World Health Organisation (WHO) classification of brain tumours and consist mainly of astrocytomas, oligodendrogliomas and oligoastrocytomas (Louis et al, 2007). The median survival for LGG is 5–10 years, but clinical outcome varies considerably (Lote et al, 1997). For some patients the disease has an indolent course for many years, whereas others experience rapid tumour progression from the time of diagnosis. Treatment is unsatisfactory and there is no cure for LGG (Soffietti et al, 2010). There is consensus but no evidence that maximal surgical resection prolongs survival in LGG (Keles et al, 2001; Duffau, 2009). A large randomised trial designed to define the optimal timing of radiotherapy showed a prolonged symptom-free survival for patients with LGG receiving adjuvant radiotherapy compared with those irradiated at progression, but no difference in overall survival (Karim et al, 2002; van den Bent et al, 2005). For optimal patient management, clinical parameters with an impact on survival have to be taken into account (Pignatti et al, 2002; Soffietti et al, 2010). Negative prognostic factors for survival are old age, astrocytoma histology, neurological deficit at presentation, large tumour diameter, contrast enhancement and tumours crossing midline (Pignatti et al, 2002). The presence of two or less unfavourable factors identifies low-risk groups, and for these low-risk patients it is probably a good strategy to defer radiotherapy until tumour progression (Pignatti et al, 2002). Many treatment decisions, however, remain unsolved. The clinical management of patients with LGG will benefit from prognostic and predictive biomarkers that can guide therapeutic decisions. One such example is the combined loss of chromosomal arms 1p/19q, the molecular hallmark of oligodendrogliomas and a strong prognostic and predictive marker in these tumours (Ohgaki and Kleihues, 2005). PROX1 is a transcription factor expressed in the heart, liver, lens, skeletal muscles, pancreas, kidney and in the CNS (Zinovieva et al, 1996). The Drosophila homologue of PROX1, prospero, resembles a tumour suppressor gene by preventing neuroblast self-renewal. In the absence of prospero, cells accumulate forming brain tumours (Betschinger et al, 2006). It has been suggested that PROX1 has a similar role in human malignancies. Decreased expression of PROX1 was found in hepatocellular carcinomas, sporadic breast cancer and carcinomas of the biliary system (Shimoda et al, 2006; Laerm et al, 2007; Versmold et al, 2007). In contrast, PROX1 was overexpressed in colorectal cancer and found to have a role in promoting cancer progression (Petrova et al, 2008). We have recently shown that PROX1 protein is overexpressed in human astrocytic tumours, with highest levels in grade III and IV astrocytomas (Elsir et al, 2010). These findings suggest that PROX1 may act as a prognostic factor in human gliomas. In the present study, we have studied the presence of PROX1 protein in correlation with patient survival in a cohort of patients with LGG.