scholarly journals The Immunohistochemical Expression of MCM-3, -5, and -7 Proteins in the Uterine Fibroids

2021 ◽  
Vol 43 (2) ◽  
pp. 802-817
Author(s):  
Piotr Rubisz ◽  
Lidia Hirnle ◽  
Christopher Kobierzycki

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.

2011 ◽  
Vol 126 (5) ◽  
pp. 460-463 ◽  
Author(s):  
K Sikka ◽  
S C Sharma ◽  
A Thakar ◽  
S Dattagupta

AbstractIntroduction:The aggressiveness of cholesteatoma in children compared with adults is well known. However, the factors influencing the poorer prognosis of paediatric cholesteatoma are not well understood. This study compared the proliferative potential of paediatric cholesteatoma with that of adult cholesteatoma, using Ki-67 as a proliferation marker.Methods:A prospective study of 67 patients with aural cholesteatoma was performed. Thirty-eight adult and 29 paediatric cases were evaluated using clinical parameters including bone erosion, complications and extent of disease. A surgical specimen underwent histological evaluation and measurement of the proliferation index using Ki-67 labelling. Normal epithelium from a control group was also examined.Results:Cholesteatoma epithelium has a greater rate of proliferation than normal skin. There were however no statistical differences between the paediatric and adult cholesteatoma groups in terms of clinical behaviour or proliferation potential. Paediatric cholesteatoma was similar to adult cholesteatoma in terms of complications, bone erosion and disease spread.Conclusion:Cholesteatoma is a disorder of epithelial proliferation. Although postulated to be more aggressive in children than adults, this study found no clinicopathological differences between paediatric and adult cases.


2016 ◽  
Vol 7 (1) ◽  
pp. 29-33 ◽  
Author(s):  
S I Askolskaya ◽  
E A Kogan ◽  
Yu V Popov ◽  
M A Solomakhina ◽  
N M Fayzullina

The endometrium may be the most convenient object of forecasting the development of the large uterine fibroid, as the object is available in the diagnosis of diseases of the uterus, changes in its cytokine profile linked with the growth of uterine fibroid. Immunohistochemically identification of high expression of Ki 67, TGF-, PD-ECGF in the endometrium allows to predict the development of large uterine fibroids.


2020 ◽  
Vol 9 (1) ◽  
pp. 1701-1706
Author(s):  
Mohammed A.A. Abdelmtalab ◽  
O. Tahir ◽  
K. Hussein ◽  
Kamal Badawi

Uterine fibroids are the commonest uterine neoplasms, they are benign tumors of smooth muscle origin. The study was done to look for the  anatomical locations of uterine fibroids and their incidence in Sudanese women at Omdurman Maternity Hospital between 1st July 2014 to 5th October 2015. Their sociodemographic and ultrasound data were collected using a prepared questionnaire. The study included 138 confirmed cases of uterine fibroids out of 2968 investigated cases representing incidence rate of 4.6%. The highest incidence was found in the age group 36-40 years. Most dominant anatomical locations of uterine fibroids were intramural as a single mass (34.78%), followed by the intramural-subserosal in multiple masses (20.29%). The anatomical positions of uterine fibroids, posterior position was seen in (27.5%) which was the most dominant in single uterine fibroid mass, followed by the anterior-posterior position in multiple uterine one (18.1%). Intramural anatomical locations in single mass are the commonest uterine fibroids types which affect the Sudanese women. Key words: Anatomical locations; Uterine fibroid and leiomyomas


2020 ◽  
Vol 10 (4) ◽  
pp. 412-415
Author(s):  
Irina Shurygina ◽  
Michael Shurygin ◽  
Elena Chepurnykh ◽  
Nataliya Ayushinova

Background: Ki-67 is a nuclear protein expressed in all proliferating cells of vertebrates during mitotic cycle phases S, G1, G2, and M, except for G0. Studying this marker is widely used to diagnose the proliferative activity of tumors. However, studying Ki-67 in non-neoplastic diseases attracts much less attention among the researchers. The aim of this study was to assess the possibility of using staining for Ki-67 to identify the proliferative potential of fibroblasts during the formation of adhesions in the abdominal cavity (AC). Methods and Results: Experiments were carried out on male Wistar rats. The adhesion process in AC was simulated in the control group (n=25), and in the experimental group (n=25) with the administration of Seroguard®. Animals were sacrificed on Days 1–30, and the severity of the adhesive process in AC was assessed. Histological sections were prepared and stained for Ki-67. It was found that the animals of the control group had increased severity of the adhesive process in AC during the observation. Maximum increase in severity was registered on Day 30 – 12[9-13] points in the control group and 4[4-4] points in the experimental group (P=0.0079). High proliferative activity of fibroblasts in the control group was detected on Days 3, 7, 14 and 30, which may indicate an active division of fibroblasts and the formation of adhesions in the damaged area. In the experimental group, single Ki-67 positive cells were noted during the entire observation period, which may point to a reduced potential for the formation of adhesions. Conclusion: Our study showed the prospects of using Ki-67 staining to determine the severity of the developing adhesive process in AC, and also revealed one of the possible mechanisms that inhibit the formation of the adhesive process when using Seroguard® – a decrease in the mitotic activity of fibroblasts in the area of peritoneal injury.


2016 ◽  
Vol 64 (1) ◽  
pp. 90-102 ◽  
Author(s):  
Izabela Janus ◽  
Marcin Nowak ◽  
Agnieszka Noszczyk-Nowak ◽  
Rafał Ciaputa ◽  
Małgorzata Kandefer-Gola ◽  
...  

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.


2019 ◽  
Vol 39 (3) ◽  
pp. 1151-1159 ◽  
Author(s):  
MICHAL APOROWICZ ◽  
PIOTR CZOPNIK ◽  
ELIZA KUBICKA ◽  
ALEKSANDRA PIOTROWSKA ◽  
PIOTR DZIEGIEL ◽  
...  

2021 ◽  
Vol 22 (7) ◽  
pp. 3618
Author(s):  
Emmanuel N. Paul ◽  
Gregory W. Burns ◽  
Tyler J. Carpenter ◽  
Joshua A. Grey ◽  
Asgerally T. Fazleabas ◽  
...  

Uterine fibroid tissues are often compared to their matched myometrium in an effort to understand their pathophysiology, but it is not clear whether the myometria of uterine fibroid patients represent truly non-disease control tissues. We analyzed the transcriptomes of myometrial samples from non-fibroid patients (M) and compared them with fibroid (F) and matched myometrial (MF) samples to determine whether there is a phenotypic difference between fibroid and non-fibroid myometria. Multidimensional scaling plots revealed that M samples clustered separately from both MF and F samples. A total of 1169 differentially expressed genes (DEGs) (false discovery rate < 0.05) were observed in the MF comparison with M. Overrepresented Gene Ontology terms showed a high concordance of upregulated gene sets in MF compared to M, particularly extracellular matrix and structure organization. Gene set enrichment analyses showed that the leading-edge genes from the TGFβ signaling and inflammatory response gene sets were significantly enriched in MF. Overall comparison of the three tissues by three-dimensional principal component analyses showed that M, MF, and F samples clustered separately from each other and that a total of 732 DEGs from F vs. M were not found in the F vs. MF, which are likely understudied in the pathogenesis of uterine fibroids and could be key genes for future investigation. These results suggest that the transcriptome of fibroid-associated myometrium is different from that of non-diseased myometrium and that fibroid studies should consider using both matched myometrium and non-diseased myometrium as controls.


Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 607
Author(s):  
Rudolfs Janis Viksne ◽  
Gunta Sumeraga ◽  
Mara Pilmane

Background and Objectives: Chronic rhinosinusitis (CRS) is a condition that affects as much as 10.9% of the population and, along with presence of nasal polyps, is associated with significant morbidity and decreased quality of life. Studies on molecular pathways that have been activated in nasal polyp tissue are mainly based on cytokine concentration detection. Therefore, our aim is to investigate the complex appearance, relative distribution and interlinks of IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 and Ki 67 in chronic rhinosinusitis with nasal polyps (CRSwNP) affected human nasal mucosa. Materials and Methods: Samples of nasal polyps were obtained from 12 patients with previously diagnosed CRSwNP and no prior surgery. Control group consisted of samples from 17 otherwise healthy individuals with isolated nasal septum deviation. Tissues were stained for IL-1, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 and Ki67 immunohistochemically. Non-parametric statistic, Mann–Whitney U test and Spearman’s rank correlation coefficient were used. Results: All factors, except connective tissue cytokine IL-10 and proliferation marker Ki-67, had increased presence in connective tissue and decreased presence in epithelium of nasal polyps when compared to controls. Very strong and strong positive correlations between factors were observed. Conclusions: Decreased appearance of IL-1α, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12 positive structures in the nasal epithelium with selective increase of IL-1α and IL-12 in nasal subepithelial connective tissue characterize the cytokine endotype with dysfunctional epithelial barrier and local stimulation of immune response in the connective tissue in case of chronic rhinosinusitis with polyps. Decrease of IL-6 in both—epithelium and connective tissue with strong correlation between it and IL-7 and IL-10 in connective tissue suggests significant stimulation of this regulatory cytokine and, possibly, the important role in pathogenesis of the development in nasal polyps. Correlations between Ki67 and cytokines indicate possible involvement of IL-4, IL-7 and IL-12 in regulation of cellular proliferation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Narine M. Tonoyan ◽  
Vitaliy V. Chagovets ◽  
Natalia L. Starodubtseva ◽  
Alisa O. Tokareva ◽  
Konstantin Chingin ◽  
...  

AbstractUterine fibroids (UF) is the most common (about 70% cases) type of gynecological disease, with the recurrence rate varying from 11 to 40%. Because UF has no distinct symptomatology and is often asymptomatic, the specific and sensitive diagnosis of UF as well as the assessment for the probability of UF recurrence pose considerable challenge. The aim of this study was to characterize alterations in the lipid profile of tissues associated with the first-time diagnosed UF and recurrent uterine fibroids (RUF) and to explore the potential of mass spectrometry (MS) lipidomics analysis of blood plasma samples for the sensitive and specific determination of UF and RUF with low invasiveness of analysis. MS analysis of lipid levels in the myometrium tissues, fibroids tissues and blood plasma samples was carried out on 66 patients, including 35 patients with first-time diagnosed UF and 31 patients with RUF. The control group consisted of 15 patients who underwent surgical treatment for the intrauterine septum. Fibroids and myometrium tissue samples were analyzed using direct MS approach. Blood plasma samples were analyzed using high performance liquid chromatography hyphened with mass spectrometry (HPLC/MS). MS data were processed by discriminant analysis with projection into latent structures (OPLS-DA). Significant differences were found between the first-time UF, RUF and control group in the levels of lipids involved in the metabolism of glycerophospholipids, sphingolipids, lipids with an ether bond, triglycerides and fatty acids. Significant differences between the control group and the groups with UF and RUF were found in the blood plasma levels of cholesterol esters, triacylglycerols, (lyso) phosphatidylcholines and sphingomyelins. Significant differences between the UF and RUF groups were found in the blood plasma levels of cholesterol esters, phosphotidylcholines, sphingomyelins and triacylglycerols. Diagnostic models based on the selected differential lipids using logistic regression showed sensitivity and specificity of 88% and 86% for the diagnosis of first-time UF and 95% and 79% for RUF, accordingly. This study confirms the involvement of lipids in the pathogenesis of uterine fibroids. A diagnostically significant panel of differential lipid species has been identified for the diagnosis of UF and RUF by low-invasive blood plasma analysis. The developed diagnostic models demonstrated high potential for clinical use and further research in this direction.


Sign in / Sign up

Export Citation Format

Share Document