Elevated expression of hyaluronan synthase 2 associates with decreased survival in diffusely infiltrating astrocytomas

Mari Valkonen,Hannu Haapasalo,Kristiina Tyynelä-Korhonen,Kirsi Rilla,Ylermi Soini,Sanna Pasonen-Seppänen

doi:10.1186/s12885-018-4569-1

Abstract

BackgroundDiffusely infiltrating astrocytomas originate from astrocytic glial cells or their precursor cells and are the most common type of brain tumors in adults. In this retrospective study, we investigated the content of hyaluronan, its cell surface receptor, CD44 and the expression of hyaluronan metabolizing enzymes, in these aggressive tumors. Hyaluronan is the main component of extracellular matrix in the brain. In many tumors, aberrant hyaluronan metabolism implicates aggressive disease progression and metastatic potential.MethodsOur material consisted of 163 diffusely infiltrating astrocytomas (WHO grades II-IV). Tumor samples were processed into tissue microarray (TMA) blocks. The TMA sections were stained for hyaluronan, CD44, hyaluronan synthases 1–3 (HAS1–3) and hyaluronidase 2 (HYAL2). The immunostaining results were compared with χ2 –test or with Kruskal-Wallis test for correlation with clinicopathological parameters and survival analyses were done with Kaplan-Meier log rank test and Cox regression.ResultsHyaluronan and CD44 were strongly expressed in astrocytic gliomas but their expression did not correlate with WHO grade or any other clinicopathological parameters whereas high HAS2 staining intensity was observed in IDH1 negative tumors (p = 0.003). In addition, in non-parametric tests increased HAS2 staining intensity correlated with increased cell proliferation (p = 0.013) and in log rank test with decreased overall survival of patients (p = 0.001). In the Cox regression analysis HAS2 expression turned out to be a significant independent prognostic factor (p = 0.008).ConclusionsThis study indicates that elevated expression of HAS2 is associated with glioma progression and suggests that HAS2 has a prognostic significance in diffusely infiltrating astrocytomas.

Highlights

Infiltrating astrocytomas originate from astrocytic glial cells or their precursor cells and are the most common type of brain tumors in adults
Our results indicate that especially HAS2 and to a lesser extent hyaluronidase 2 (HYAL2) and HAS1 are involved in the progression of diffusely infiltrating astrocytomas
We show that HAS1, HAS2 and HYAL2 are associated with WHO grade, suggesting that they have a role in tumor progression

Summary

Introduction

Infiltrating astrocytomas originate from astrocytic glial cells or their precursor cells and are the most common type of brain tumors in adults. In this retrospective study, we investigated the content of hyaluronan, its cell surface receptor, CD44 and the expression of hyaluronan metabolizing enzymes, in these aggressive tumors. Hyaluronan is directly extruded through the plasma membrane to the cell surface or into the extracellular matrix [1]. Infiltrating astrocytomas are the most common type of gliomas. They are Valkonen et al BMC Cancer (2018) 18:664 divided into three categories (grades II-IV) by WHO [11, 12]. Knockdown of CD44 in glioblastoma cell lines decreases tumor growth and sensitizes them to cytotoxic drugs [17]

Methods

Results

Discussion

Conclusion