scholarly journals Lymphocyte-macrophage colonization in various molecular biological types of endometrial cancer: comparison with the receptor status and proliferative activity of tumor tissue

2021 ◽  
Vol 67 (3) ◽  
pp. 405-410
Author(s):  
Lev Bershtein ◽  
Aleksandr Ivantsov ◽  
Aglaia Ievleva ◽  
Dmitrii Vasilev ◽  
Igor` Berlev
Keyword(s):  
Endometrial Cancer ◽  
Proliferative Activity ◽  
Activity Index ◽  
Immunohistochemical Analysis ◽  
Lymphocytic Infiltration ◽  
Molecular Profile ◽  
Ki 67 ◽  
Dna Polymerase Epsilon ◽  
Macrophage Marker ◽  
Mmr Proteins

Recent years have been marked by a gradual shift from the previous division of endometrial cancer (EC) into two main types to modern molecular biological classifications of this disease, one of which (at present, most likely, the most popular: Talhouk et al., 2017, 2019) is based on the use of a combination of genetic and immunohistochemical analysis. The study involved material from untreated EC patients, the number of which varied depending on the method used. The average age of patients was close to 55-60 years, and over 80% of patients were postmenopausal. Deparaffinized blocks of EC tissue were analyzed for POLE (DNA polymerase epsilon) mutations, evaluated by immunohistochemistry (IHC) the expression of the oncoprotein p53 and MMR (mismatch-repair) proteins / MLH1, MSH2, MSH6 and PMS2 /, and also helped to identify the type of disease without a characteristic molecular profile (WCMP). In addition to studying the expression of p53 and MMR proteins, the IHC method was also used to study the expression of estrogen (ER) and progesterone (PR) receptors, the Ki-67 proliferative activity index, and the severity of macrophage-lymphocytic infiltration of the EC tissue based on the analysis of the macrophage marker (CD68) and markers of lymphocytic cells (cytotoxic CD8 and regulatory FoxP3) using reagents from Ventana and Dako.

scholarly journals Markers of Lymphocytic-Macrophagal Infiltration and Their Association With the Receptor Phenotype and Proliferative Activity of Tumor Tissue in Various Molecular-Biological Types of Endometrial Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1026-A1026
Author(s):  
Lev M Berstein ◽  
Alexander O Ivantsov ◽  
Aglaya Iyevleva
Keyword(s):  
Endometrial Cancer ◽  
Proliferative Activity ◽  
Tumor Tissue ◽  
Practical Importance ◽  
Rank Correlation ◽  
Macrophage Infiltration ◽  
Proliferation Index ◽  
Molecular Profile ◽  
Ki 67 ◽  
Receptor Phenotype

Abstract Background and Aims: The last years were characterized by a shift from the former subdivision of endometrial cancer (EC) into two main types [1, 2] to modern molecular biological classifications of this disease [3-5]. The purpose of this investigation was an attempt to compare such prognostic indicators for EC as features of lymphocytic [6] and macrophage infiltration of tumor tissue with markers of its hormonal sensitivity (receptor phenotype) and the proliferation index Ki-67 [7], taking into account the molecular biological type of the disease. Materials and Methods: The study involved material from untreated patients with endometrial cancer (a total of 219 people). The average age of patients was close to 55-60 years. Using classification of Talhouk et al. [5] allowed to perform a search for POLE mutations, evaluate by IHC the expression of the oncoprotein p53 and MMR (mismatch-repair) proteins /MLH1, MSH2, MSH6 and PMS2/, and also identify the type of disease without a characteristic molecular profile (WCMP). The IHC method was also used to study the rate of estrogen (ER) and progesterone (PR) receptors, Ki-67 proliferative activity index, as well as the severity of macrophage-lymphocytic tissue infiltration of EC based on the analysis of the macrophage (CD68) and lymphocytic cells (cytotoxic CD8 and regulatory FoxP3) markers using reagents from Ventana and Dako. Statistical assessment of the relationships of the studied indicators was carried out by the Spearman rank correlation coefficient. Results: FoxP3 (in contrast to CD8 and CD68) positively and significantly correlates (ρ varies from 0.2895 to 0.3477) more often with ER, but not with PR. Ki-67 index in EC tissue positively and reliably correlates with FoxP3 both in the MMR-D and WCMP groups and in the combined cohort of EC patients. In the latter case, a similar relationship with Ki-67 extends to other studied markers of lymphocytic-macrophage infiltration, namely CD8 and CD68 (ρ 0,1746-0,3294). Only in the entire group of EC patients there is a positive rank correlation (0.4119!) between ER and PR expression. Conclusions: In patients with certain types of EC the connection between the estrogenic signal and PR induction is lost; it is especially noticeable in the MMR-D group, as exemplified by the negative correlation (-0.2951) of FoxP3 and PR expression. Taken together with existing data this indicates an important role of the endocrine component for differentiating separate groups of patients with EC, that may also be of practical importance. References: 1. Bokhman JV. Gynecol Oncol 1983; 15: 10-17. 2. Suarez AA et al. Gynecol Oncol 2017;144(2):243-249. 3. Murali R et al. Lancet Oncol 2014; 15: e268-278. 4.Berstein LM et al. Future Oncol. 2017 13(28):2593-2605. 5. Talhouk A. et al. Cancer. 2017;123(5):802-813. 6. Gargiulo P. et al. Cancer Treat Rev. 2016;48:61-8. 7. Kitson S. et al. Mod Pathol. 2017; 30(3): 459-468.

scholarly journals Immunohistochemical characteristics of breast cancer, increasing the risk of local reccurence after organosaving treatment

2018 ◽  
Vol 14 (3) ◽  
pp. 10-14
Author(s):  
S. M. Demidov ◽  
D. A. Demidov ◽  
S. V. Sazonov ◽  
E. I. Churakova
Keyword(s):  
Breast Cancer ◽  
Proliferative Activity ◽  
Receptor Gene ◽  
Molecular Genetic ◽  
Statistical Processing ◽  
Immunohistochemical Analysis ◽  
Recurrent Tumor ◽  
Ki 67 ◽  
Epidermal Growth ◽  
Triple Negative Subtype

Objective:an immunohistochemical analysis of the characteristics of a recurrent tumor in breast cancer.Materials and methods.The statistical processing of immunohistochemical analysis’ results was performed and the most frequently encountered molecular-genetic subtypes of breast cancer with the development of local relapses were formulated. The analysis used a standard immunohistochemical panel, which is the “gold standard” for diagnostic in Russia today, and includes the expression of receptors for sex hormones (estrogen and progesterone), expression of the human epidermal growth factor HER2/neu receptor gene, and the index of proliferative activity Ki-67. The 2nd stage of the work was the evaluation of the dynamics of changes in the immunohistochemical characteristics of a recurrent tumor in comparison with the primary one.Results and conclusion.The most common local recurrence provides by triple-negative subtype of breast cancer (42 %). The changes in the immunohistochemical characteristics of a recurrent tumor in comparison with the primary one affected only the index of proliferative activity Ki-67 in the direction of its increase by 12 %.

scholarly journals The Value of Diffusion-weighted Magnetic Resonance Imaging in the Preoperative Evaluation of the Grade of Brain Gliomas

2019 ◽  
Vol 100 (2) ◽  
pp. 102-110
Author(s):  
V. A. Byvaltsev ◽  
I. A. Stepanov ◽  
A. I. Kichigin
Keyword(s):  
Cell Density ◽  
Proliferative Activity ◽  
Activity Index ◽  
Preoperative Evaluation ◽  
Proliferative Potential ◽  
Ki 67 ◽  
Diffusion Weighted ◽  
Significant Difference ◽  
The Mean ◽  
Brain Gliomas

Objective. To compare the values obtained for the measured diffusion coefficient (MDC) of brain gliomas with cell density and Ki-67 proliferative activity index and to study whether diffusion-weighted MRI (DWMRI) can be used in the preoperative evaluation of the grade of glial tumors.Material and methods. Diffusion-weighted images of 39 patients with brain gliomas were studied. MDC, cell density, and Ki-67 proliferative activity index were calculated for each tumor. The correlation between MDC values, cell density, and Ki-67 proliferative activity index was analyzed.Results. Comparison of the mean values for MDC revealed a significant difference between grades I–II and III–IV tumors. There were statistically significant differences in the mean Ki-67 index between different grades of gliomas. Evaluation of the correlation between MCD and Ki-67 proliferative activity index demonstrated moderate and strong inverse correlations for low- and high-grade tumors, respectively.Conclusion. The procedure using DW-MRI along with MDC calculation can be used as an additional noninvasive method for the preoperative estimation of the grade and proliferative potential of brain gliomas.

scholarly journals Immunohistochemical Study of Tumor Cells Proliferative Activity at Different Graduations of Prostate Cancer

2019 ◽  
Vol 23 (4) ◽  
pp. 364-372 ◽  
Author(s):  
G. Y. Kudryavtsev ◽  
L. V. Kudryavtseva ◽  
L. M. Mikhaleva ◽  
I. I. Babichenko
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Proliferative Activity ◽  
Immunohistochemical Study ◽  
Activity Index ◽  
Clinical Stage ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Ki 67 ◽  
Degree Of Differentiation

Prostate cancer is one of the leading causes of men death in developed countries. Modern diagnostic methods, including a puncture biopsy of the prostate gland, make it possible to verify oncology in the early stages, however, routine studies do not always allow to predict the course of the disease and outcome. The aim of our study was to analyze the clinical, morphological and immunohistochemical features of the proliferative activity of adenocarcinoma cells using the Ki-67 marker, to compare the degree of proliferative activity in tumors of various degrees of malignancy (according to Gleason’s classification), as well as to compare this indicator with the clinical stage of the disease, the level of prostate-specific antigen in the blood, the size of the prostate gland. Materials and Methods: On the basis of the City Clinical Hospital No. 31 and the Veteran Hospital No. 2, paraffin blocks with material obtained as a result of prostate biopsy, transurethral resection, and radical prostatectomy were selected. A morphological and immunohistochemical study of the material with the Ki-67 marker and a quantitative assessment of the degree of proliferative activity were carried out. Data were analyzed using the STATISTICA 10.0 program using estimates of the normality of the data distribution according to the Shapiro-Wilk W-test, the significance of differences was estimated using the Mann-Whitney U-test, and correlation relationships using Spearman’s correlation coefficient. Results: Statistically significant differences in the degree of proliferative activity in groups differing in the degree of differentiation were revealed. A statistically significant direct correlation of moderate severity was revealed when comparing proliferative activity with the degree of differentiation according to the Gleason system (rs = 0.523) and the clinical stage of the disease (rs = 0.646). No statistically significant correlation was found between indicators such as prostate-specific antigen level, age, prostate volume, and proliferative activity index. Conclusion: taking into account the proliferative activity index in addition to clinical and morphological studies helps to diagnose and subsequently predict the course of prostate cancer.

scholarly journals SUN-133 Intratumoral Expression of Steroid Receptors, CD68+ Macrophages and Mdm2 in Different Molecular-Biological Types of Endometrial Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lev M Berstein ◽  
Alexander Ivantsov ◽  
Dmitry Vasilyev ◽  
Aglaya Iyevleva
Keyword(s):  
Endometrial Cancer ◽  
Tumor Cells ◽  
Tumor Tissue ◽  
Steroid Receptors ◽  
Signal Transmission ◽  
Protein A ◽  
Immunohistochemical Analysis ◽  
Negative Regulator ◽  
Molecular Profile ◽  
P53 Expression

Abstract Background and aims : In Risk Classifier for Endometrial Cancer/EC (ProMisE) 4 molecular biological types of this tumor are described recently [1,2,3] and need an additional research, including evaluation of hormone-associated characteristics of both tumor tissue and patients [4]. Aim of the work was a study of estrogen (ER) and progesterone (PR) receptors in comparison with CD68+ macrophage infiltration (which promotes the invasion of tumor cells into the myometrium [5]) and expression of MDM2 protein, a negative regulator of p53 [6], in EC types presented in the ProMisE classification. Materials and methods: The tumor tissue of 218 EC patients included in the study (mean age 60.6 years) was assigned according to the data of genetic and immunohistochemical analysis to the types of carcinomas with gene POLE mutations, deficiency of mismatch repair proteins (MMR-D), expression (positive or diffuse) of p53 oncoprotein and to the type without characteristic molecular profile, WCMP. Immunohistochemistry was used also for evaluation of ER (Ventana antibodies, clone SP1) and PR (Ventana antibodies, clone 1E2) according to Allred, MDM2 (antibodies ABCAM, dilution 1:200) and macrophage marker CD68 (DAKO antibodies, clone CD8/144B). Results: According to the averaged data, the highest expression of ER and PR was found in EC types MMR-D and WCMP, and the lowest, respectively, in types POLE and p53+. Most often, positive expression of MDM2 (in 93.2% and 96.9% of studied cases) was detected respectively in MMR-D and p53+ type of EC, indicating, therefore, a positive relationship between MDM2 and the presence of steroid receptors in the first of these types (MMR-D) and negative - in the second of them (p53+). Expression of CD68+ macrophages demonstrated (contrary to the EC types POLE and p53+) a tendency to the lower values in types MMR-D and WCMP (128.0 ± 8.1 and 113.5 ± 6.3 cond.un.), i.e. in tumors with potential sensitivity to estrogen. Conclusions: The results indicate the importance of taking into account of both - the molecular biological type of the EC as well as the role of microenvironment of tumor cells, including the colonization of the neoplasm’ tissue by macrophages (and possibly lymphocytes) and the features of hormonal signal transmission in it. For further analysis, it is desirable to consider also the EC histotype, as one of the factors underlying various prognostic groups of this tumor [7]. References: 1.Talhouk A, McAlpine JN. Gynecol Oncol Res Pract. 2016; 3:14. 2. Talhouk et al., Cancer. 2017; 123(5):802–813. 3. Kommoss FK et al., Br J Cancer. 2018;119(4):480–486. 4. Berstein et al. Future Oncol. 2019; 15(12):1335–1346. 5. Jing X. et al. Immunol Cell Biol. 2019; 97(6):563–576. 6. Zou X. et al. Medicine (Baltimore).2018;97(49):e13273. 7. Bosse T. et al. Am J Surg Pathol. 2018 May;42(5):561–568.

scholarly journals The effects of fetal neural cell conditioned medium on cell proliferation in the rat brain after traumatic brain injury

2021 ◽  
Vol 9 (2) ◽  
Author(s):  
M. Lisyany ◽  
◽  
D. Stanetska ◽  
I. Govbakh ◽  
O. Tsupykov ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rat Brain ◽  
Cell Cultures ◽  
Proliferative Activity ◽  
Immunohistochemical Analysis ◽  
Subcortical Structures ◽  
Adhesive Properties ◽  
Ki 67 ◽  
The Brain

Traumatic brain injury (TBI) is accompanied by an increase in the number of proliferating cells. However, the question of the nature, conditions of production and mechanisms of action of humoral factors secreted by fetal neural cells (FNCs) on reparative processes and neurogenesis in the brain after trauma and FNCs transplantation remains open. The purpose of the study was to establish the possibility of the influence of the conditioned medium of fetal neural cell cultures on the proliferative activity of Ki-67-positive cells in the cortex and subcortical structures of the rat brain after TBI. Materials and methods. TBI was simulated by dropping a metal cylinder on the rat’s head. Rats (E17-18) were used to obtain cultures of neural stem/progenitor cells. Conditioned media from cell cultures with high adhesive properties (HA-CM) and low adhesive properties (LA-CM) were used to treat the effects of experimental TBI in rats by intramuscular injection. The effect of conditioned media on the proliferative activity of Ki-67-positive cells in the cortex and subcortical structures of the brain after TBI was determined by immunohistochemical analysis using antibodies against Ki-67 protein. Results. Immunohistochemical analysis of the brain sections showed that on the 5th day after traumatic brain injury in rats there was a probable increase in the number of Ki-67-positive cells in the cortex, hippocampus and thalamus. It was found that the injection of HA-CM or LA-CM in animals with TBI increased the number of Ki-67-positive cells in the hippocampus compared with the TBI group and their value for the TBI+LA-CM group reached 59.6 ± 6.1, and for the TBI+HA-CM group – 47.2 ± 3.1 cells (p <0.05 compared with the TBI group). In the cortex and thalamus, the number of Ki-67-positive cells in contrast decreased compared with the group of animals with TBI and for the group TBI+LA-CM was 20.2 ± 1.6 and 12.0 ± 1.7, respectively, and for the group TBI+HA-CM – 25.3 ± 2.1 and 13.3 ± 1.3, respectively. Conclusions. The administration of LA-CM or HA-CM to animals with traumatic brain injury increases the number of Ki-67-positive cells in the hippocampus, possibly associated with increased neurogenesis, and decreases in the cortex and thalamus, which may be due to a weakening of reactive gliosis.

scholarly journals Proliferative Activity of Human Thyroid Cells in Various Age Groups and Its Correlation with the Risk of Thyroid Cancer after Radiation Exposure

2006 ◽  
Vol 91 (7) ◽  
pp. 2672-2677 ◽  
Author(s):  
Ali G. Saad ◽  
Seena Kumar ◽  
Elaine Ron ◽  
Jay H. Lubin ◽  
Jerzy Stanek ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Proliferative Activity ◽  
Age Groups ◽  
Inverse Correlation ◽  
Immunohistochemical Analysis ◽  
Human Thyroid ◽  
Ki 67 ◽  
Thyroid Cells ◽  
Proliferative Rate

Abstract Context: The thyroid gland is vulnerable to the carcinogenic effects of ionizing radiation, and there is a well-documented inverse correlation between thyroid cancer and age at exposure, particularly for ages less than 20 yr. One of the factors responsible for this phenomenon may be more rapid cell proliferation in children. Objective: The objective of this study was to determine the proliferative rate of normal human thyroid cells in different age groups. Design: We used immunohistochemical analysis to determine the Ki-67 proliferative index in 117 thyroid glands obtained at autopsy, including 25 fetal thyroids (11–40 wk gestation), 55 childhood thyroids (0–19 yr), and 37 adult thyroids (20–60 yr). Results: The rate of Ki-67 labeling in the three groups was 7.4 ± 6.10, 0.23 ± 0.15, and 0.08 ± 0.04% respectively, demonstrating an overall trend for diminishing proliferative activity of thyroid cells with increasing age. However, a lack of correlation was noted between the slopes of cancer risk calculated from previous studies of irradiated populations and proliferative rate in the pediatric age intervals of 0–4 and 5–9 yr, suggesting that other factors are likely to be responsible for the particularly high sensitivity to radiation-induced thyroid cancer among the youngest children. Conclusions: Our findings of a general decrease in proliferative activity of thyroid cells with age may explain, at least in part, the higher risks of radiation-related thyroid cancer in children compared with adults. However, the variation in the rate of cell proliferation is unlikely to be responsible entirely for this phenomenon and other factors may also be involved.

An immunohistochemical analysis of lymphocytic infiltrations in canine skin cancers

2017 ◽  
Vol 20 (1) ◽  
pp. 141-147 ◽  
Author(s):  
J.A. Madej ◽  
J.P. Madej ◽  
S. Dzimira ◽  
M. Nowak
Keyword(s):  
Squamous Cell Carcinoma ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immunohistochemical Analysis ◽  
Lymphocytic Infiltration ◽  
Sebaceous Gland Carcinoma ◽  
Ki 67 ◽  
Inflammatory Infiltration ◽  
Keratinizing Squamous Cell Carcinoma

Abstract Lymphocytic infiltrations located in the extracellular matrix often accompany canine skin cancer. They can be characterised as an inflammatory infiltration and/or a second tumour - lymphoma. The aim of this study was an immunohistochemical analysis of a lymphocytic infiltration which accompanies spontaneous skin cancer. Twenty basal cell carcinoma, 20 non-keratinizing squamous cell carcinoma, 20 keratinizing squamous cell carcinoma and 8 sebaceous gland carcinoma samples which were accompanied by a lymphocytic infiltration and/or secondary lymphatic follicles were verified histopathologically. The expression of bcl-2, CD3, CD79α, Ki-67, MCM-3 and MCM-7 in the lymphocytic infiltration was evaluated. Four types of lymphocytic infiltrations were found: I - diffuse bcl-2+, II - diffuse bcl-2-, III - follicular bcl-2+/- where the centre was bcl-2-, and the marginal zone of the follicles and the extrafollicular area were bcl-2+ and IV - aggregated bcl-2+, where the centre and periphery were bcl-2+. The I and IV type corresponds to lymphoma, II type is non-neoplastic immune response and III type suggest reactive follicular hyperplasia. The proliferation of lymphocytes which demonstrated the expression of neoplastic markers (I and IV), suggests preneoplastic phase (pseudolymphoma) or lymphoma - the second independent tumour. A high proliferative index of the follicular blc-2+/- follicular infiltration indicates an increased immunological response of the host against skin cancer.

Retrospective immunohistochemical study of VDR, RXR, Ki-67, and Bcl-2 expression in primary and metastatic osteosarcoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e21516-e21516 ◽  
Author(s):  
O. Tawfik ◽  
R. Garimella ◽  
J. Tancabelic ◽  
J. Keighley ◽  
D. Pinson ◽  
...  
Keyword(s):  
Proliferative Activity ◽  
Therapeutic Option ◽  
Immunohistochemical Analysis ◽  
Antineoplastic Activity ◽  
Retinoid Receptor ◽  
Ki 67 ◽  
Primary Tumors ◽  
Cellular Events ◽  
Biologic Effect ◽  
Histologic Types

e21516 Background: Osteosarcoma (OS) is a highly malignant tumor with a peak incidence in adolescents and young adults. Patient's prognosis is limited to clinical parameters whereas molecular markers of tumor aggression are yet to be identified. Vitamin D (Vit D) has been postulated as a novel therapeutic option for a variety of malignancies such as breast and prostatic carcinomas. The biologic effect of vitamins is mainly mediated through receptors. Vit D receptors (VDRs) are members of the steroid hormone superfamily and are ubiquitous in a various tissues including bone. Upon activation by its ligand, VDR combines with retinoid receptor (RXR) forming a heterodimer initiating a cascade of cellular events. How Vit D induces its antineoplastic activity in OS remains to be elucidated. Methods: Immunohistochemical analysis for VDR, RXR, Ki-67, and bcl-2 was performed on 87 OS specimens to evaluate differentiation, proliferation and apoptosis. Clinical data including site of the primary tumor, presence or absence of metastasis, therapeutic regimens, and outcome were recorded. Results: The mean age of OS patients is 25.7 years (range 7–68). Fifty-four patients were <30 years. Thirty-five OSs were conventional, 17 chondroblastic, 6 giant cell, 6 fibroblastic, 6 mixed, 3 telangiectatic, and 2 epithelioid variants. Twelve of the 87 samples were metastatic. All metastatic OSs were high grade, located in the lungs with a mean age of 25 years (range 7–52). The majority of the OSs expressed VDR (74/87, 85%) and RXR (72/78, 92%). Proliferative activity varied between tumors types with highest Ki-67 percentage noticed in conventional variant (29%), followed by chondroblastic variant (16%). Metastatic tumors consistently had the highest proliferative activity as compared to primary tumors (35%). None of the tumors studied was immunoreactive for bcl-2. Conclusions: Our results demonstrate that VDR and RXR are expressed on most OSs. A significant relationship exists between tumor histologic types and proliferative activity. Metastatic OSs appears to have a significantly higher level of proliferative activity as compared to primary tumors. These results would establish a foundation for elucidating mechanisms by which Vit D induces its antineoplastic activity in OS. No significant financial relationships to disclose.

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