YKL-40 (CHI3-L1) A NOVEL PROGNOSTIC BIOMARKER IN WHO GRADE III ANAPLASTIC GLIOMAS
Abstract
Introduction: YKL-40, also known as Chitinase-3-like protein 1 (CHI3L1), has been proposed as a novel prognostic biomarker in numerous cancers including gliomas. There are very few studies/ reports detailing the prognostic value of YKL-40 in WHO grade III anaplastic gliomas (AG), or its correlation with the clinically established diffuse glioma biomarkers; IDHmutation and 1p19q codeletion and the WHO 2016 histomolecular subgroups. In this study we evaluated the expression of YKL40 in AGs and assessed its prognostic significance in a single large cohort of Indian patients, within the diagnostic subgroups of AGs i.e., AO (1p19q codeleted and IDH mutant), AA IDHmutant and AA IDHwild type subgroups.
Methods: Immunohistochemistry was performed for YKL-40 expression on the retrospective cohort of anaplastic gliomas (AGs)(n=91), which had been molecularly stratified as AO,IDH mutant, 1p19q codeleted; AA IDH mutant and AA IDH wild type subgroups from our previous published study(1).
Results: YKL-40 immunopositivity was strong cytoplasmic with nil to weak nuclear staining of the tumor cells and was seen in 38 (41.76%) cases, whereas the remaining 53(58.24%) were negative, and although the majority of AO and AA IDHmutant lacked YKL-40 expression, all the AA IDHwild type tumors were YKL-40 positive. Further, YKL-40 immunopositivity had a statistically significant negative correlation with both the clinically established favorable prognostic markers 1p19q codeletion and IDH mutation and a very strong positive correlation with the IDHwild type genotype.YKL40 was associated with a shorter overall and recurrence free survival in AG patients(p<0.001)
Conclusions: In conclusion, we show that YKL-40 is a marker of poor prognosis in AGs and all its subgroups. YKL-40 expression shows a negative correlation with IDH mutation and 1p19q codeletion and positive correlation with IDH wild type genotype, suggesting this marker to be biologically aggressive in AGs.
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