Expression of Minichromosome Maintenance MCM6 Protein in Meningiomas is Strongly Correlated With Histologic Grade and Clinical Outcome

Abstract

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 World Health Organization classification, there are 4 parameters on the basis of which grade II status can be determined: mitotic rate, cytoarchitectural features, brain invasion, and/or histologic subtype. Furthermore, this classification fails to detect grade I recurrent meningiomas, for which other prognostic criteria would be needed. 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 of 59, grade II: 27 of 59, all harboring ≥4 mitoses/1.6 mm), analyzed with the following immunohistochemical markers: MCM6, Ki-67, PHH3, cyclin D1, and p53. We found a significant correlation between histologic grade and mean labeling index for MCM6 (grade I: 21.8% vs. grade II: 65.8%; P<0.001), Ki-67 (3.2% vs. 16.9%; P<0.001), PHH3 (0.7‰ vs. 2.8‰; P<0.001), cyclin D1 (50.4% vs. 70.0%; P=0.005), and p53 (17.3% vs. 32.4%; P=0.017). 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 for cyclin D1 (P=0.400) and p53 (P=0.758). The interobserver agreement coefficients for MCM6, Ki-67, PHH3, cyclin D1, and p53 were, respectively, 0.97 (95% confidence interval, 0.95-0.98), 0.93 (0.89-0.96), 0.81 (0.70-0.88), 0.90 (0.83-0.94), and 0.84 (0.73-0.90). In conclusion, because of 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 a high risk of recurrence.

GTSE1, CDC20, PCNA, and MCM6 Synergistically Affect Regulations in Cell Cycle and Indicate Poor Prognosis in Liver Cancer

“…The minichromosome maintenance protein (MCM) family is implicated in the control of eukaryotic genome replication and proves to be useful markers for tumor proliferation [24]. Several studies demonstrated overexpression of MCM6 also predicts poor survival in patients with several types of cancer, including HCC [31][32][33][34]. Future studies should attempt to clarify the underlying mechanism of GTSE1 together with minichromosome-related protein-mediated DNA replication and cancer prognosis.…”

Methyl(R217)HuR and MCM6 are inversely correlated and are prognostic markers in non small cell lung carcinoma

“…Interestingly, Martin et al, in a systematic review with meta-analysis, concluded Ki-67 to be a bad prognosis marker for survival in 15 out of 37 studies [1]. Among other proliferation markers, the mini-chromosome maintenance (MCM) proteins -key proteins in the initiation of DNA synthesis and DNA replication -were shown to be associated with histological grades in various neoplastic processes [4]. In lung cancer, few studies have evaluated the prognostic value of the MCMs proteins, including MCM2, MCM4, and MCM7 [2,5,6].…”

Plasma minichromosome maintenance complex component 6 is a novel biomarker for hepatocellular carcinoma patients

“…13 Recent reports have showed that increased expression of MCM family proteins are related to several tumors including HCC. [14][15][16][17] For example, detection of stool MCM can be used for detection of colorectal cancer, 14 MCM5 is used in diagnosis of pancreaticobiliary malignancy in bile aspirates, 15 expression of MCM6 protein in meningiomas is strongly correlated with histological grade and clinical outcome, 16 MCM7 expression also predicts postoperative prognosis for HCC. 17 Our previous results also indicated that MCM6 is overexpressed in HCC tissues.…”