Minichromosome Maintenance Proteins MCM-3, MCM-5, MCM-7, and Ki-67 as Proliferative Markers in Adrenocortical Tumors

Uterine fibroids are the most common mesenchymal uterine neoplasms; their prevalence is estimated in 40%–60% of women under 35 and in 70%–80% of women over 50 years of age. The current research aims to focus on the etiopathogenesis of uterine fibroids, the factors that affect their growth, and markers with diagnostic and prognostic properties. The MCM (minichromosome maintenance) protein family consists of peptides whose primary function is participation in the molecular mechanism of creating replication forks while regulating DNA synthesis. The aim of this work was to determine the proliferative potential of uterine fibroid cells based on the expression of the Ki-67 antigen and the MCMs—i.e., MCM-3, MCM-5, and MCM-7. In addition, the expression of estrogen (ER) and progesterone (PgR) receptors was evaluated and correlated with the expression of the abovementioned observations. Ultimately, received results were analyzed in terms of clinical and pathological data. Materials and methods: In forty-four cases of uterine fibroids, immunohistochemical reactions were performed. A tissue microarray (TMA) technique was utilized and analyzed cases were assessed in triplicate. Immunohistochemistry was performed using antibodies against Ki-67 antigen, ER, PgR, MCM-3, MCM-5, and MCM-8 on an automated staining platform. Reactions were digitalized by a histologic scanner and quantified utilizing dedicated software for nuclear analysis. Assessment was based on quantification expression of the three histiospots, each representing one case in TMA. Results: In the study group (uterine fibroids), statistically significant stronger expression of all the investigated MCMs was observed, as compared to the control group. In addition, moderate and strong positive correlations were found between all tested proliferative markers. The expression of the MCM-7 protein also correlated positively with ER and PgR. With regard to clinical and pathological data, there was a negative correlation between the expression of MCMs and the number of both pregnancies and births. Significant reductions in MCM-5 and MCM-7 expression were observed in the group of women receiving oral hormonal contraceptives, while smoking women showed an increase in MCM-7, ER, and PgR. Conclusions: Uterine fibroid cells have greater proliferative potential, as evaluated by expression of the Ki-67 antigen and MCMs, than unaltered myometrial cells of the uterine corpus. The expression of MCM-7 was found to have strong or moderate correlations in all assessed relations. In the context of the clinical data, as well evident proliferative potential of MCMs, further studies are strongly recommended.

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Epidemiological and pathological features of primary cardiac tumours in dogs from Poland in 1970–2014

Acta Veterinaria Hungarica ◽

10.1556/004.2016.010 ◽

2016 ◽

Vol 64 (1) ◽

pp. 90-102 ◽

Cited By ~ 2

Author(s):

Izabela Janus ◽

Marcin Nowak ◽

Agnieszka Noszczyk-Nowak ◽

Rafał Ciaputa ◽

Małgorzata Kandefer-Gola ◽

...

Keyword(s):

Positive Reaction ◽

Immunohistochemical Analysis ◽

Histopathological Diagnosis ◽

Beta Catenin ◽

Minichromosome Maintenance ◽

Ki 67 ◽

Routine Diagnostics ◽

Cardiac Tumours ◽

Cardiac Neoplasms ◽

Proliferative Markers

Primary heart tumours affect less than 1% of dogs. Due to their rare incidence, every research showing the frequency of cardiac tumours is valuable. Routine diagnostics is often complemented with immunohistochemical analysis. This study was conducted on 110 patient records from all veterinary faculties in Poland from dogs diagnosed with heart tumours between 1970 and 2014. The dogs’ age, breed and sex with tumour localisation and histopathological diagnosis were analysed. Because of its most common incidence, samples of haemangiosarcoma underwent further examination with assessment of the expression of cell markers that have not been evaluated earlier (i.e. minichromosome maintenance proteins and beta-catenin). We noted 111 tumours including 88.3% malignant and 10.8% benign ones. Haemangiosarcoma and aortic body tumour were the most frequent cardiac neoplasms in the dogs examined (45.9% and 27.9% of all tumours, respectively). Immunohistochemical analysis of haemangiosarcoma showed a positive expression of all markers examined. CD31, vimentin, and beta-catenin showed a positive reaction in all 11 samples examined. At least one proliferative marker (Ki-67, MCM-3 or MCM-7) showed a positive reaction in each sample. MCM-3 showed a higher expression than the two other proliferative markers (P = 0.006), but only Ki-67 showed a positive correlation with the mitotic index (P > 0.05, r = 0.89). Although beta-catenin, MCM-3 and MCM-7 showed a positive reaction in the haemangiosarcomas examined, their usefulness as diagnostic and prognostic factors should be a topic of further research.

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Aberrant expression of minichromosome maintenance proteins 2 and 5, and Ki-67 in dysplastic squamous oesophageal epithelium and Barrett's mucosa

Gut ◽

10.1136/gut.50.3.373 ◽

2002 ◽

Vol 50 (3) ◽

pp. 373-377 ◽

Cited By ~ 99

Author(s):

J J Going

Keyword(s):

Minichromosome Maintenance ◽

Ki 67 ◽

Aberrant Expression ◽

Barrett’S Mucosa ◽

Barrett's Mucosa

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Significance of cell proliferation markers (Minichromosome maintenance protein 7, topoisomerase IIα and Ki-67) in cavital fluid cytology: Can we differentiate reactive mesothelial cells from malignant cells?

Diagnostic Cytopathology ◽

10.1002/dc.21190 ◽

2009 ◽

pp. NA-NA ◽

Cited By ~ 1

Author(s):

Fumikazu Kimura ◽

Jumpei Kawamura ◽

Jun Watanabe ◽

Shingo Kamoshida ◽

Kenji Kawai ◽

...

Keyword(s):

Cell Proliferation ◽

Mesothelial Cells ◽

Malignant Cells ◽

Minichromosome Maintenance ◽

Topoisomerase Iiα ◽

Ki 67 ◽

Proliferation Markers ◽

Minichromosome Maintenance Protein ◽

Fluid Cytology

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Clinicopathological description of 43 oncocytic adrenocortical tumors: importance of Ki-67 in histoprognostic evaluation

Modern Pathology ◽

10.1038/s41379-018-0077-8 ◽

2018 ◽

Vol 31 (11) ◽

pp. 1708-1716 ◽

Cited By ~ 8

Author(s):

Karine Renaudin ◽

◽

Sarra Smati ◽

Matthieu Wargny ◽

Abir Al Ghuzlan ◽

...

Keyword(s):

Ki 67 ◽

Adrenocortical Tumors

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DNA Topoisomerase II-α and Cyclin A Immunoexpression in Meningiomas and Its Prognostic Significance

Archives of Pathology & Laboratory Medicine ◽

10.5858/2002-126-1079-dtiaca ◽

2002 ◽

Vol 126 (9) ◽

pp. 1079-1086

Author(s):

Andrey Korshunov ◽

Lyudmila Shishkina ◽

Andrey Golanov

Keyword(s):

Topoisomerase Ii ◽

Tumor Grade ◽

Cyclin A ◽

Close Correlation ◽

Hazard Ratio ◽

Benign Tumors ◽

Ki 67 ◽

Dna Topoisomerase ◽

Proliferative Markers ◽

Topoisomerase Ii Α

Abstract Context.—Routine pathologic examination cannot distinctively predict the clinical course of meningiomas because even histologically benign tumors may recur after gross total resection. Therefore, numerous efforts have been made to evaluate the meningioma growth fraction and its prognostic value. However, a universally applicable proliferative marker for meningioma outcome is not yet a reality. Objective.—To investigate the prognostic utility of 3 proliferative markers, namely, Ki-67, DNA topoisomerase II-α (topoII), and cyclin A in a representative series of intracranial meningiomas. Design.—Two hundred sixty-three adult patients with intracranial meningiomas (208 benign, 42 atypical, and 13 anaplastic) were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to Ki-67 (MM-1), topoII, and cyclin A. A computerized color image analyzer was used to count immunostained nuclei. Results.—The topoII and cyclin A scores exhibited a close correlation with Ki-67 immunostaining. Significant differences between the indices for all 3 markers were noted among the 3 grades of meningiomas. The scores for all 3 markers were significantly different between recurrent and nonrecurrent meningiomas, including benign tumors that were treated with gross total resection. Recurrence-free survival was significantly reduced for cases with a Ki-67 labeling index (LI) of 4.4% or greater, a topoII LI of 3.2% or greater, and a cyclin A LI of 3.1% or greater. Multivariate analysis revealed that the risk of recurrence for the entire meningioma cohort was significantly associated with tumor grade (hazard ratio = 2.7; P = .004), topoII LI of 3.2% or greater (hazard ratio = 5.5; P < .001), and a cyclin A LI of 3.1% or greater (hazard ratio = 2.4; P = .01). Conclusions.—There is a close correlation in the expression of these 3 proliferative markers in meningiomas, and all of the markers showed a significant association with tumor grade, recurrence rate, and recurrence-free survival. Consequently, in addition to Ki-67, immunoexpression of topoII and cyclin A is available for predicting meningioma recurrence. Moreover, the topoII and cyclin A staining scores were found to be more sensitive predictors for meningioma progression than Ki-67 and, therefore, either of these 2 markers may prove to be clinically informative and useful.

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