The superior prognostic role of pRB1 over p16 immunohistochemistry as a biomarker in meningiomas

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BACKGROUND: Despite best clinical management, patients with meningiomas frequently experience tumor recurrence. During recent decades, efforts have been made to improve the prognostic stratification of meningiomas by incorporating molecular data. A subgroup of tumors harboring a homozygous CDKN2A deletion was identified, and a higher risk of tumor progression was observed, suggesting the potential use of cyclin-dependent kinases as biomarkers. MATERIAL AND METHODS: In this retrospective single-center study, the immunohistochemical staining for the cyclin-dependent kinases p16, phosphoRB1 (pRB1), CDK4 and CDK6 was analyzed in 1751 paraffin-embedded meningioma samples. For the assessment of p16, CDK4 and CDK6, a semi-quantitative score was applied, whereas an automated quantification tool was used for pRB1. The distribution and association with histopathological results, clinical data and progression-free survival (PFS)-defined by radiographic tumor recurrence-were assessed. RESULTS: Of all meningioma samples, 14.9% (n = 261) expressed p16. Elevated pRB1 levels were found in 34.5% (n = 589) of tumor samples. CDK4 and CDK6 positive staining was observed in 41.9% and 42.2% of cases, respectively. Dichotomous stratification of meningiomas based on p16 and pRB1 expression levels suggested a significant influence on PFS in univariate analyses. Multivariate analysis determined elevated pRB1 expression, WHO grading, extent of resection, adjuvant radiotherapy, male gender, NF2-status and an elevated MIB1 index as independent prognostic factors. CONCLUSIONS: High expression of pRB1 is an independent prognostic factor for shorter PFS. The prognostic impact of p16 is mostly attributed to the confounding increase of pRB1 expression.

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