Expression of Mini-Chromosome Maintenance MCM6 Protein in Meningiomas Is Strongly Correlated with Histological Grade and Clinical Outcome
Guillaume Gauchotte, Charlene Vigouroux, Fabien Rech, Shyue-Fang Battaglia-Hsu, Marc Soudant, Catherine Pinelli, Thierry Civit, Luc Taillandier, Jean-Michel Vignaud, Aude Bressenot. CHU, Nancy, France; Medical Faculty of Nancy, Nancy, France
Background: The 2007 World Health Organization histologic grading of meningiomas is associated with recurrence and clinical outcome. However, distinction of grade I from grade II (atypical) meningiomas can be challenging. In the WHO classification, there are 4 ways to achieve grade II status: mitotic rate, cyto-architectural features, brain invasion and/or histological subtype. Furthermore, this classification fails to detect grade I recurrent meningiomas, for which other prognostic criteria would be needed.
Design: The aim of this study was to evaluate the respective value of several markers involved in cell cycle as effective tools to predict recurrence. This retrospective study was based on a series of 59 meningiomas (grade I: 32/59; grade II: 27/59, all harboring ≥4 mitoses/1.6 mm²), analyzed with the following immunohistochemical markers: MCM6, Ki-67, PHH3, cyclin D1 and p53.
Results: We found a significant correlation between histologic grade and mean labeling index for MCM6 (grade I: 21.8% vs grade II: 66.4%; p<0.001), Ki-67 (3.2% vs 16.3%; p<0.001), PHH3 (0.7‰ vs 2.7‰; p=0.010), cyclin D1 (50.4% vs 70.0%; p=0.004) and p53 (17.3% vs 32.4%; p<0.001). Histologic grading and mitotic index were correlated with progression-free survival (p=0.010 and p=0.020, respectively). A nearly linear correlation was found between progression-free survival and staining for MCM6 (p<0.001), Ki-67 (p=0.003) and PHH3 (p=0.037), but not cyclin D1 (p=0.400) and p53 (p=0.763). The inter-observer agreement coefficients for MCM6, Ki-67, PHH3, cyclin D1 and p53 were respectively 0.97 (95%CI: 0.95-0.98), 0.93 (0.89-0.96), 0.81 (0.71-0.88), 0.87 (0.80-0.92) and 0.84 (0.73-0.90).
Conclusions: In conclusion, due to its strong level of expression and sharp difference in labeling index between indolent and recurrent tumors, MCM6 is the most efficient marker to identify tumors with high risk of recurrence.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 266, Tuesday Afternoon