Evaluation of Minichromosome Maintenance Protein 7 and c-KIT as Prognostic Markers in Feline Cutaneous Mast Cell Tumours

Background Magnetic resonance (MR) spectroscopy (1H-MRS) has been demonstrated to be useful in grading glioma, but the utility in assessing cellular proliferation activity and prognosis correlated with the expression of minichromosome maintenance protein 2 (MCM2) has not been reported. Purpose To explore the correlation between proton MR spectroscopy parameters (including choline [Cho]/creatine [Cr], N-acetyl aspartate [NAA]/Cr, and Cho/NAA ratios) and the expression of MCM2 and to further evaluate whether 1H-MRS can predict cell proliferative activity and provide prognostic information in high-grade gliomas (HGGs). Material and Methods Forty-three patients with histopathologically confirmed gliomas were involved in this study. All patients underwent 1H-MRS examination before surgery. Proliferative activity of gliomas was evaluated by MCM2 labeling index (LI). Pearson correlation analysis and empiric receiver operating characteristic (ROC) curves were performed. The Kaplan–Meier method and Cox regression were used for survival analysis. Results Significant correlation was observed between the Cho/Cr ratio and MCM2 LI ( r = 0.522, P < 0.01); however, there was no correlation between MCM2 LI and the Cho/NAA or NAA/Cr ratios ( r = 0.295, P = 0.55 and r = −0.042, P = 0.788, respectively). According to ROC analysis, MCM2 LI of 50% and Cho/Cr ratio of 2.68 represented the optimized cut-off values, respectively, to distinguish longer or shorter survival than 15 months in HGGs patients. Multivariate analysis revealed that both the Cho/Cr ratio and MCM2 expression were independent prognostic markers. Conclusion Cho/Cr ratio has a potential in predicting the expression of MCM2 and can evaluate cell proliferative activity noninvasively. Both the Cho/Cr ratio and MCM2 expression are independent prognostic markers in patients with HGGs.

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Minichromosome Maintenance Protein (MCM6) in Low-Grade Chondrosarcoma: Distinction From Enchondroma and Identification of Progressive Tumors

Yearbook of Orthopedics ◽

10.1016/s0276-1092(08)70547-9 ◽

2006 ◽

Vol 2006 ◽

pp. 274

Author(s):

C.P. Beauchamp

Keyword(s):

Low Grade ◽

Minichromosome Maintenance ◽

Minichromosome Maintenance Protein

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Bi-allelic MCM10 variants associated with immune dysfunction and cardiomyopathy cause telomere shortening

Nature Communications ◽

10.1038/s41467-021-21878-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ryan M. Baxley ◽

Wendy Leung ◽

Megan M. Schmit ◽

Jacob Peter Matson ◽

Lulu Yin ◽

...

Keyword(s):

Immune Cell ◽

Nk Cell ◽

Restrictive Cardiomyopathy ◽

Telomerase Activity ◽

Compound Heterozygous ◽

Minichromosome Maintenance ◽

Telomere Shortening ◽

Clinical Phenotypes ◽

Eukaryotic Dna ◽

Minichromosome Maintenance Protein

AbstractMinichromosome maintenance protein 10 (MCM10) is essential for eukaryotic DNA replication. Here, we describe compound heterozygous MCM10 variants in patients with distinctive, but overlapping, clinical phenotypes: natural killer (NK) cell deficiency (NKD) and restrictive cardiomyopathy (RCM) with hypoplasia of the spleen and thymus. To understand the mechanism of MCM10-associated disease, we modeled these variants in human cell lines. MCM10 deficiency causes chronic replication stress that reduces cell viability due to increased genomic instability and telomere erosion. Our data suggest that loss of MCM10 function constrains telomerase activity by accumulating abnormal replication fork structures enriched with single-stranded DNA. Terminally-arrested replication forks in MCM10-deficient cells require endonucleolytic processing by MUS81, as MCM10:MUS81 double mutants display decreased viability and accelerated telomere shortening. We propose that these bi-allelic variants in MCM10 predispose specific cardiac and immune cell lineages to prematurely arrest during differentiation, causing the clinical phenotypes observed in both NKD and RCM patients.

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Stereology in Grading and Prognosis of Canine Cutaneous Mast Cell Tumors

Veterinary Pathology ◽

10.1177/0300985820985138 ◽

2021 ◽

pp. 030098582098513

Author(s):

Mafalda Casanova ◽

Sandra Branco ◽

Inês Berenguer Veiga ◽

André Barros ◽

Pedro Faísca

Keyword(s):

Mast Cell ◽

Clinical Outcome ◽

Prognostic Value ◽

Histological Grade ◽

Intraobserver Variability ◽

Low Grade ◽

High Grade ◽

Mast Cell Tumors ◽

Cutaneous Mast Cell ◽

Grade Iii

Canine cutaneous mast cell tumors (ccMCTs) are currently graded according to Patnaik and Kiupel grading schemes. The qualitative and semiquantitative parameters applied in these schemes may lead to inter- and intraobserver variability. This study investigates the prognostic value of volume-weighted mean nuclear volume ([Formula: see text]), a stereological estimation that provides information about nuclear size and its variability. [Formula: see text] of 55 ccMCTs was estimated using the “point-sampled intercept” method and compared with histological grade and clinical outcome. The clinical history of dogs treated with surgical excision alone was available for 30 ccMCTs. Statistical differences in [Formula: see text] were found between grade II ([Formula: see text]= 115 ± 29 µm3) and grade III ccMCTs ([Formula: see text]= 197 ± 63 µm3), as well as between low-grade ([Formula: see text]= 113 ± 28 µm3) and high-grade ccMCTs ([Formula: see text]= 184 ± 63 µm3). An optimal cutoff value of [Formula: see text] ≥ 150 µm3 and [Formula: see text] ≥ 140 µm3 was determined for grade III and high-grade ccMCTs, respectively. In terms of prognosis, [Formula: see text] was not able to predict the clinical outcome in 42% of the cases; however, cases with [Formula: see text]<125 µm3 had a favorable outcome. These results indicate that, despite having limited prognostic value when used as a solitary parameter, [Formula: see text] is highly reproducible and is associated with histological grade as well as with benign behavior.

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