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YKL-40 Is a Differential Diagnostic Marker for Histologic Subtypes of High-Grade Gliomas

¹ Molecular Neuro-Oncology Laboratory and Molecular Pathology Unit, Departments of Pathology, Cancer Center, and Neurosurgical Service; ² Brain Tumor Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School; and ³ Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts

Requests for reprints: David N. Louis, Molecular Pathology Unit, CNY7, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129. Phone: 617-726-5690; Fax: 617-726-5079; E-mail: dlouis{at}partners.org.

Purpose and Experimental Design: In modern neuro-oncology, no variable affects therapeutic decisions and prognostic estimation more than tumor classification. We showed recently that class prediction models, based on gene expression profiles, classify diagnostically challenging malignant gliomas in a manner that better correlates with clinical outcome than standard pathology. In the present study, we used immunohistochemistry to investigate YKL-40 protein expression in independent sets of glioblastomas and anaplastic oligodendrogliomas to determine whether this single marker can aid classification of these high-grade gliomas.

Results and Conclusions: Glioblastomas show strikingly more YKL-40 expression than anaplastic oligodendrogliomas. Only 2 of 37 glioblastomas showed completely negative YKL-40 staining in both tumor cells and extracellular matrix, whereas 18 of 29 anaplastic oligodendrogliomas were completely negative in non-microgemistocytic tumor cells and extracellular matrix. Tumor cell staining intensity was also markedly different: 84% of glioblastomas showed strong staining intensities of 2+ or 3+ whereas 76% of anaplastic oligodendrogliomas either did not stain or stained at only 1+. YKL-40 staining provided a better class distinction of glioblastoma versus anaplastic oligodendroglioma than glial fibrillary acidic protein, the current standard immunohistochemical marker used to distinguish diagnostically challenging gliomas. Moreover, a combination of YKL-40 and glial fibrillary acidic protein immunohistochemistry afforded even greater diagnostic accuracy in anaplastic oligodendrogliomas.

Key Words: Brain/central nervous system cancers • Molecular diagnosis and prognosis

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