Correlations between surface marker patterns in meningiomas, prognosis and location

BACKGROUND: Meningiomas exhibit considerable phenotypic variation within each WHO grade, thus additional markers are needed to identify prognostically relevant subgroups and optimize long-term management. Among biomarkers, genetic signatures correlate with prognoses. High Ki-67 proliferation indices and TERT promotor mutations and loss of CDKNA are known prognostic markers. Yet, such markers were mainly established by correlative analyses between biomarker expression and retrospective clinical data.

METHODS: Our group has reported on expression of a panel of markers in 176 meningiomas from 170 meningioma patients who underwent surgery from 2005 to 2008 in a previous publication. The markers were growth hormone receptor, insulin-like growth factor 1 receptor, progesterone receptor (PR), CD34, androgen receptor, epidermal growth factor receptor E30, caspase 3, and vascular endothelial growth factor (VEGF). Of the 176 meningiomas, 159 were classified as WHO grade 1, 16 were WHO grade 2 and one was WHO grade 3. We have now surveyed outcome after >10 years. We analyzed possible correlations between marker expression and clinical data such as recurrence, tumor location and patient death.

RESULTS: 27 of 155 WHO grade 1 and 5 of 15 WHO grade 2 meningiomas recurred. No statistically significant correlations between marker expression and recurrence were observed. The 10-year mortality was 10,8% and 53,4% for WHO grade 1 and 2, respectively, with 47 % and 50 % being disease specific for meningioma. A statistically significant negative correlation was observed between PR expression and death related to the tumor (50 % PR expression vs. 89 % in those not dying from the tumor; p = 0.001). Additionally, Ki-67 values showed to be higher in tumors of patients dying from the tumor (8 % vs. 4 %, p = 0.001). A statistically significant relationship was observed between PR and central/skull base (70 % expression in central/skull base vs. 39 % in other locations, p = 0,0002).

CONCLUSIONS: During 10-year follow-up, tumor recurrence was an important cause of death, accounting for approximately half of follow-up mortality despite the benign grading of meningiomas. This ambitious, prospective observational study failed to identify expression of GHr, Igf1r, CD34, EGFR, caspase 3 and VEGF as clinically relevant biomarkers.