Gene expression analyses of grade II gliomas and identification of rPTP/ as a candidate oligodendroglioma marker

¹ Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
² Department of Neuroscience, Uppsala University, Uppsala University Hospital, Uppsala, Sweden
³ Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden
⁴ Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden
⁵ Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden, and Department of Pathology, Helsinki University and University Hospital, Helsinki, Finland

^* To whom correspondence should be addressed. E-mail: arne.ostman{at}ki.se.

	Abstract

Grade II gliomas are morphologically and clinically heterogeneous tumors for which histopathological typing remains the major tool for clinical classification. To what extent the major histological subtypes--astrocytomas, oligodendrogliomas, and oligoastrocytomas--constitute true biological entities is largely unresolved. Furthermore, morphological classification is often ambiguous and would be facilitated by specific subtype markers. In this study, 23 grade II gliomas were expression-profiled and subjected to hierarchical clustering. All six oligodendrogliomas were grouped together in one of two major clusters; a significant correlation was thus observed between gene expression and histopathological subtype. Supervised analyses were performed to identify genes differentiating oligodendrogliomas from other grade II tumors. In a leave-one-out test using 10 features for classification, 20 out of 23 tumors were correctly classified. Among the most differentially expressed genes was rPTP/. The expression of the rPTP / protein in oligodendrogliomas and astrocytomas was further validated by immunohistochemistry in an independent set of tumors. All 11 oligodendrogliomas of this set displayed strong staining. In contrast, neoplastic astrocytes were mostly negative for rPTP/ staining. In summary, this study demonstrates a correlation between gene expression pattern and histological subtype in grade II gliomas. Furthermore, the results from the immunohistochemical analyses of rPTP/ expression should prompt further evaluation of this protein as a novel oligodendroglioma marker.

Key Words: Grade II glioma, histological marker, microarray, oligodendroglioma, rPTP/