Pub Date : 2023-01-01DOI: 10.31088/cem2023.12.1.5-14
A. V. Lagureva, N. Plekhova, V. Apanasevich
Breast cancer is the leading cause of oncological morbidity in women worldwide, but its causes are still being investigated. The researchers hypothesized a possible association between breast cancer and viral infection. Some studies support this assumption, while others point out their inconclusiveness. The aim of the review was to study the association of human papillomavirus (HPV) and Epstein–Barr (EBV) infection in breast tumors. We analyzed the results of more than 100 publications demonstrating the relation between HPV and EBV infections and breast tumors of different origin. Data on the presence of viral particles were obtained by various methods: IHC, real-time PCR, and in situ hybridization, where formalin-fixed tissues were studied. We detected HPV and EBV DNA and studied the expression of HPV oncoproteins (E6, L1) and EBV latent antigens (EBNA-1, EBNA-2, EBNA-3, LMP-1). The analysis of more than 4,000 cases of benign and malignant breast tumors indicates a wide range of HPV and EBV prevalence in breast tissue (up to 86% and 56%, respectively). Despite the revealed relations between the presence of viral particles in tissues and the subsequent tumor development, the etiological role of HPV and EBV in the occurrence and progression of breast tumors remains debatable. Keywords: breast tumor, breast cancer, human papillomavirus (HPV), Epstein–Barr virus (EBV), oncoviruses
{"title":"Role of HPV and Epstein–Barr virus in the development of epithelial breast tumors","authors":"A. V. Lagureva, N. Plekhova, V. Apanasevich","doi":"10.31088/cem2023.12.1.5-14","DOIUrl":"https://doi.org/10.31088/cem2023.12.1.5-14","url":null,"abstract":"Breast cancer is the leading cause of oncological morbidity in women worldwide, but its causes are still being investigated. The researchers hypothesized a possible association between breast cancer and viral infection. Some studies support this assumption, while others point out their inconclusiveness. The aim of the review was to study the association of human papillomavirus (HPV) and Epstein–Barr (EBV) infection in breast tumors. We analyzed the results of more than 100 publications demonstrating the relation between HPV and EBV infections and breast tumors of different origin. Data on the presence of viral particles were obtained by various methods: IHC, real-time PCR, and in situ hybridization, where formalin-fixed tissues were studied. We detected HPV and EBV DNA and studied the expression of HPV oncoproteins (E6, L1) and EBV latent antigens (EBNA-1, EBNA-2, EBNA-3, LMP-1). The analysis of more than 4,000 cases of benign and malignant breast tumors indicates a wide range of HPV and EBV prevalence in breast tissue (up to 86% and 56%, respectively). Despite the revealed relations between the presence of viral particles in tissues and the subsequent tumor development, the etiological role of HPV and EBV in the occurrence and progression of breast tumors remains debatable. Keywords: breast tumor, breast cancer, human papillomavirus (HPV), Epstein–Barr virus (EBV), oncoviruses","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69281055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.31088/cem2023.12.1.15-23
A. Proshchina, A. Kharlamova, Y. Krivova, S. Saveliev
Brain atlases are widely used to determine relative location, form, and a number of other parameters of certain brain structures. Such data are required in medical practice, fundamental neuroscience research, and educating graduate and postgraduate medical students. Many papers observed the development of human brain atlases. However, recently numerous new atlases have been published, both digital and online ones. This tendency was triggered by intensive development and growing accessibility of modern visualization tools and digitizing novel data and existing archives. This study aimed to overview the historical background of and modern tendencies in the brain atlas development for Russian readers. Furthermore, foreign literature does not focus on Russian neurological tradition, so we attempted to cover this issue as well. Particular attention is paid to the atlases of human brain development. Keywords: human brain atlas, human prenatal development
{"title":"Modern trends in brain mapping and atlasing","authors":"A. Proshchina, A. Kharlamova, Y. Krivova, S. Saveliev","doi":"10.31088/cem2023.12.1.15-23","DOIUrl":"https://doi.org/10.31088/cem2023.12.1.15-23","url":null,"abstract":"Brain atlases are widely used to determine relative location, form, and a number of other parameters of certain brain structures. Such data are required in medical practice, fundamental neuroscience research, and educating graduate and postgraduate medical students. Many papers observed the development of human brain atlases. However, recently numerous new atlases have been published, both digital and online ones. This tendency was triggered by intensive development and growing accessibility of modern visualization tools and digitizing novel data and existing archives. This study aimed to overview the historical background of and modern tendencies in the brain atlas development for Russian readers. Furthermore, foreign literature does not focus on Russian neurological tradition, so we attempted to cover this issue as well. Particular attention is paid to the atlases of human brain development. Keywords: human brain atlas, human prenatal development","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69280852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction. Today, well-differentiated gastric neuroendocrine tumors (GNETs)–previously known as carcinoids–have been detected 10 times more frequently in the last 30–35 years, and their prognosis has significantly improved over this time. Type 1 GNETs includes 70 to 80% of gastric neuroendocrine neoplasms and is associated with chronic atrophic autoimmune gastritis (AIH) and enterochromaffin-like (ECL) cell hyperplasia. Materials and methods. During a 5-year follow-up period from 2017 to 2022, AIH was diagnosed in 155 patients according to the database of the Clinical Center of Sechenov University. This study included 34 cases in which the presence of AIH was proven and the tumors were classified as type 1 GNETs. The age of the patients ranged from 37 to 75 years, the median one being 57 years. Results. Type 1 GNETs was more often observed in women aged 50–60 years and in 77% of cases, presented multifocal polypoid neoplasms of the mucous membrane (<10 mm) in the gastric body and/or fundus. All tumors were well-differentiated and structured in solid and trabecular-tubular patterns. Proliferative activity (Ki-67, MIB-1 index) was below 3%. Seventy-four percent of type 1 GNETs were limited to the mucosa and 26% invaded the submucosa. Tumors were detected incidentally before AIH was diagnosed in 25 cases. GNETs diagnoses were made with previously confirmed AIH in 9 cases. The GNET sizes varied from 0.15 to 1.8 cm (average 0.8 mm). The prevalence of type 1 GNETs in patients with AIH was 22% (34 out of 155 patients having AIH). We considered only neoplasms larger than 0.5 cm and excluded cases of dysplasia. The total number of cases was 15 (9.7%). Conclusion. In patients with AIH in the altered atrophic mucosa of the gastric body, one should strive to identify hyperplastic and especially dysplastic changes in ECL cells indicating an increased risk of developing GNETs that require adequate endoscopic treatment and/or follow-up. Patients with type 1 GNETs of 1 cm or less in diameter and no risk factors such as muscle wall infiltration, high proliferation index (>3%), and/or blood vessel invasion, can be operated on with minimally invasive sparing techniques and a flexible endoscope and/or conservatively in regular instrumental and laboratory monitoring. Keywords: neuroendocrine tumor, carcinoid, stomach, dysplasia, autoimmune gastritis
{"title":"Gastric neuroendocrine tumors in patients with autoimmune gastritis","authors":"A.S. Tertychnyy, М.V. Mnikhovich, D.P. Nagornaya, P.V. Pavlov, A.P. Kiryukhin, A.A. Fedorenko, А.A. Sakha","doi":"10.31088/cem2023.12.3.19-27","DOIUrl":"https://doi.org/10.31088/cem2023.12.3.19-27","url":null,"abstract":"Introduction. Today, well-differentiated gastric neuroendocrine tumors (GNETs)–previously known as carcinoids–have been detected 10 times more frequently in the last 30–35 years, and their prognosis has significantly improved over this time. Type 1 GNETs includes 70 to 80% of gastric neuroendocrine neoplasms and is associated with chronic atrophic autoimmune gastritis (AIH) and enterochromaffin-like (ECL) cell hyperplasia. Materials and methods. During a 5-year follow-up period from 2017 to 2022, AIH was diagnosed in 155 patients according to the database of the Clinical Center of Sechenov University. This study included 34 cases in which the presence of AIH was proven and the tumors were classified as type 1 GNETs. The age of the patients ranged from 37 to 75 years, the median one being 57 years. Results. Type 1 GNETs was more often observed in women aged 50–60 years and in 77% of cases, presented multifocal polypoid neoplasms of the mucous membrane (<10 mm) in the gastric body and/or fundus. All tumors were well-differentiated and structured in solid and trabecular-tubular patterns. Proliferative activity (Ki-67, MIB-1 index) was below 3%. Seventy-four percent of type 1 GNETs were limited to the mucosa and 26% invaded the submucosa. Tumors were detected incidentally before AIH was diagnosed in 25 cases. GNETs diagnoses were made with previously confirmed AIH in 9 cases. The GNET sizes varied from 0.15 to 1.8 cm (average 0.8 mm). The prevalence of type 1 GNETs in patients with AIH was 22% (34 out of 155 patients having AIH). We considered only neoplasms larger than 0.5 cm and excluded cases of dysplasia. The total number of cases was 15 (9.7%). Conclusion. In patients with AIH in the altered atrophic mucosa of the gastric body, one should strive to identify hyperplastic and especially dysplastic changes in ECL cells indicating an increased risk of developing GNETs that require adequate endoscopic treatment and/or follow-up. Patients with type 1 GNETs of 1 cm or less in diameter and no risk factors such as muscle wall infiltration, high proliferation index (>3%), and/or blood vessel invasion, can be operated on with minimally invasive sparing techniques and a flexible endoscope and/or conservatively in regular instrumental and laboratory monitoring. Keywords: neuroendocrine tumor, carcinoid, stomach, dysplasia, autoimmune gastritis","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135840361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.31088/cem2023.12.1.77-86
M. N. Boltovskaya, G. Tabeeva, N. Tikhonova, V. Aleksankina, A. Asaturova, P. Vishnyakova, T. Fatkhudinov
Introduction. One of the most challenging problems faced in gynecology is Asherman’s syndrome (AS), characterized by the formation of intrauterine adhesions, partial or complete obliteration of the uterine cavity with scar tissue, and the loss of the functional layer of the endometrium following intrauterine interventions. Treatments for AS are not always effective. This indicates a need to search and evaluate the effectiveness of new approaches to the prevention of fibrosis and stimulation of endometrial regeneration. According to ethical principles, this is possible only when simulating AS on laboratory animals. The aim of the work is to develop an etiologically adequate model of AS in Sprague Dawley rats. Materials and methods. We simulated AS in 18 female Sprague Dawley rats that were divided into 3 groups (6 rats in each). Operations were performed in the estrus phase. We made longitudinal incision of the right uterine horns, and the endometrium was scraped out to the inner layer of the myometrium with the scalpel. Groups 1 and 2 underwent only endometrial scraping. In group 3 abdominal cavities were opened on day 7 after curettage and intrauterine adhesions were destroyed with a needle inserted into the horn. Then, the standard procedure for suturing surgical wound was performed. The animals were removed from the experiment on days 7 (group 1) and 15 (groups 2 and 3) after the surgery with an overdose of ether anesthesia. The tissue samples of the operated and non-operated uterine horns were fixed with 10% buffered formalin and embedded in paraffin; the sections were stained with hematoxylin and eosin. Results. Macroscopic examination on day 7 after the surgery showed that all females had a compaction and contraction of the operated area of the uterine horn and uterine cavity fluid. On day 15, fluid collection was more pronounced. After the destruction of the uterine adhesions in rats from group 3, there was no fluid collection or it was less voluminous than in females of other groups. Histological examination showed that on days 7 and 15 after endometrial curettage, the uterine cavity and the luminal epithelium covering it were absent due to complete replacement by connective tissue. Uterine glands were not detected or were individual. On day 7 after the destruction of the adhesions and on day 15 after endometrial scraping the subjects developed a small stenosed uterine cavity lined with luminal epithelium or a larger uterine cavity containing single or multiple adhesions covered with epithelium. The number of glands was significantly smaller than in the non-operated horn. Conclusion. To simulate Asherman’s syndrome, female Sprague Dawley rats in the estrus phase were scraped out of the endometrial layer of the right uterine horn. On days 7 and 15 after surgery, the uterine cavity and luminal epithelium were absent due to complete replacement with connective tissue, which proves the formation of intrauterine adhesions and the adequacy of t
{"title":"Development of an experimental model of endometrial pathology (Asherman’s syndrome)","authors":"M. N. Boltovskaya, G. Tabeeva, N. Tikhonova, V. Aleksankina, A. Asaturova, P. Vishnyakova, T. Fatkhudinov","doi":"10.31088/cem2023.12.1.77-86","DOIUrl":"https://doi.org/10.31088/cem2023.12.1.77-86","url":null,"abstract":"Introduction. One of the most challenging problems faced in gynecology is Asherman’s syndrome (AS), characterized by the formation of intrauterine adhesions, partial or complete obliteration of the uterine cavity with scar tissue, and the loss of the functional layer of the endometrium following intrauterine interventions. Treatments for AS are not always effective. This indicates a need to search and evaluate the effectiveness of new approaches to the prevention of fibrosis and stimulation of endometrial regeneration. According to ethical principles, this is possible only when simulating AS on laboratory animals. The aim of the work is to develop an etiologically adequate model of AS in Sprague Dawley rats. Materials and methods. We simulated AS in 18 female Sprague Dawley rats that were divided into 3 groups (6 rats in each). Operations were performed in the estrus phase. We made longitudinal incision of the right uterine horns, and the endometrium was scraped out to the inner layer of the myometrium with the scalpel. Groups 1 and 2 underwent only endometrial scraping. In group 3 abdominal cavities were opened on day 7 after curettage and intrauterine adhesions were destroyed with a needle inserted into the horn. Then, the standard procedure for suturing surgical wound was performed. The animals were removed from the experiment on days 7 (group 1) and 15 (groups 2 and 3) after the surgery with an overdose of ether anesthesia. The tissue samples of the operated and non-operated uterine horns were fixed with 10% buffered formalin and embedded in paraffin; the sections were stained with hematoxylin and eosin. Results. Macroscopic examination on day 7 after the surgery showed that all females had a compaction and contraction of the operated area of the uterine horn and uterine cavity fluid. On day 15, fluid collection was more pronounced. After the destruction of the uterine adhesions in rats from group 3, there was no fluid collection or it was less voluminous than in females of other groups. Histological examination showed that on days 7 and 15 after endometrial curettage, the uterine cavity and the luminal epithelium covering it were absent due to complete replacement by connective tissue. Uterine glands were not detected or were individual. On day 7 after the destruction of the adhesions and on day 15 after endometrial scraping the subjects developed a small stenosed uterine cavity lined with luminal epithelium or a larger uterine cavity containing single or multiple adhesions covered with epithelium. The number of glands was significantly smaller than in the non-operated horn. Conclusion. To simulate Asherman’s syndrome, female Sprague Dawley rats in the estrus phase were scraped out of the endometrial layer of the right uterine horn. On days 7 and 15 after surgery, the uterine cavity and luminal epithelium were absent due to complete replacement with connective tissue, which proves the formation of intrauterine adhesions and the adequacy of t","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69281129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction. The rapid spread of the COVID-19 pandemic caused by SARS-CoV-2 initially indicated a significant immune system involvement, including peripheral blood leukocytes. Hematologic changes have already been described in the first cases of COVID-19; however, only few studies reported morphological cell abnormalities in peripheral blood smears. The aim of the study was to characterize the morphology of peripheral blood leukocytes in patients with COVID-19 and determine the significance of its changes in the immune system dysfunction and for the disease diagnosis. Materials and methods. We studied blood samples of 30 patients infected by SARS-CoV-2 virus (confirmed with PCR tests) who were treated in Regional Clinical Hospital No. 2 in Vladivostok. Peripheral blood buffy coat samples fixed in osmium tetroxide were embedded in epoxy with subsequent preparation of semithin and ultrathin sections. Results. To the best of our knowledge, it is the first study to show nuclear pathological changes in neutrophils and monocytes in blood buffy coat of the patients with coronavirus infection with light and electron microscopy of peripheral blood. We found cells with abnormal nuclear shape and leukocyte apoptotic degeneration absent in healthy individuals. The identified morphological leukocyte abnormalities should be considered as signs of hyporeactivity of these cells, which indirectly indicate a decrease in their bactericidal potential in COVID-19. At the same time, the secretory degranulation of neutrophils with the release of the contents of the granules into the extracellular space was poorly visualized. We observed smooth plasmalemma of leukocytes with a small number of microvilli involved in phagocytosis and numerous apoptotic leukocytes with reduced phagocytic ability. Conclusion. The detection of morphological abnormalities of circulating leukocytes in patients with COVID-19 is of diagnostic and prognostic value in this pathology. Keywords: blood, neutrophils, monocytes, morphology, COVID-19, SARS-CoV-2, karyopathological changes
{"title":"Morphology of peripheral blood leukocytes in patients with new coronavirus infection (COVID-19)","authors":"L.M. Somova, E.I. Drobot, E.V. Pustovalov, S.A. Abramova, N.G. Plekhova, A.I. Simakova, S.A. Sokotun, A.O. Mikhailov, I.N. Lyapun, M.Yu. Shchelkanov","doi":"10.31088/cem2023.12.3.41-49","DOIUrl":"https://doi.org/10.31088/cem2023.12.3.41-49","url":null,"abstract":"Introduction. The rapid spread of the COVID-19 pandemic caused by SARS-CoV-2 initially indicated a significant immune system involvement, including peripheral blood leukocytes. Hematologic changes have already been described in the first cases of COVID-19; however, only few studies reported morphological cell abnormalities in peripheral blood smears. The aim of the study was to characterize the morphology of peripheral blood leukocytes in patients with COVID-19 and determine the significance of its changes in the immune system dysfunction and for the disease diagnosis. Materials and methods. We studied blood samples of 30 patients infected by SARS-CoV-2 virus (confirmed with PCR tests) who were treated in Regional Clinical Hospital No. 2 in Vladivostok. Peripheral blood buffy coat samples fixed in osmium tetroxide were embedded in epoxy with subsequent preparation of semithin and ultrathin sections. Results. To the best of our knowledge, it is the first study to show nuclear pathological changes in neutrophils and monocytes in blood buffy coat of the patients with coronavirus infection with light and electron microscopy of peripheral blood. We found cells with abnormal nuclear shape and leukocyte apoptotic degeneration absent in healthy individuals. The identified morphological leukocyte abnormalities should be considered as signs of hyporeactivity of these cells, which indirectly indicate a decrease in their bactericidal potential in COVID-19. At the same time, the secretory degranulation of neutrophils with the release of the contents of the granules into the extracellular space was poorly visualized. We observed smooth plasmalemma of leukocytes with a small number of microvilli involved in phagocytosis and numerous apoptotic leukocytes with reduced phagocytic ability. Conclusion. The detection of morphological abnormalities of circulating leukocytes in patients with COVID-19 is of diagnostic and prognostic value in this pathology. Keywords: blood, neutrophils, monocytes, morphology, COVID-19, SARS-CoV-2, karyopathological changes","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135840590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.31088/cem2023.12.3.28-40
A.Yu. Kalinchuk, L.A. Tashireva, V.M. Perelmuter
Introduction. M1 and M2 macrophages in the tumor microenvironment are known to express programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1). It can determine disease outcomes and tumor response to treatment including immunotherapy. However, the macrophage composition of the breast cancer microenvironment and its relation to various clinical and pathological features have been only partially studied. The aim of the study was to detect the PD-1 and PD-L1 expression features in M1 and M2 macrophages in breast cancer patients depending on menstruation, tumor size, molecular subtype, lymph node metastases, and hematogenous metastases. Materials and methods. The study included 19 patients with breast cancer. Using seven-color multiplex TSA-modified immunohistochemistry, we identified M1 macrophages (CD68+CD163–CD3–CKAE1/3–), M2 macrophages (CD68+/–CD163+CD3–CKAE1/3–), and PD-1 and PD-L1 expression in the macrophages. Results. The macrophage composition of the breast carcinoma microenvironment varies in PD-1 and PD-L1 expression. M1 macrophages are more characteristic to show their expression, and it does not depend on the molecular subtype and the presence of hematogenous metastases. Simultaneously, the relative number of macrophages with phenotypes PD1–PDL1+ M1 and PD1+PDL1+ M2 was higher in patients with tumor size corresponding to T2 compared to T1. Differences in macrophage composition were found in patients depending on the lymph node involvement. Patients without lymph node metastases had virtually no PD-1 expression in M2 macrophages in contrast to patients with them. Conclusion. Breast cancer was shown to have phenotypic variety of macrophages in the tumor microenvironment. Moreover, macrophage composition was diverse in different individuals. Initially, a different composition of macrophages is characteristic of patients with different tumor sizes and different lymph node involvement. Keywords: breast cancer, M1 macrophages, M2 macrophages, PD-L1, PD-1
{"title":"M1 and M2 macrophage phenotypic diversity in the tumor microenvironment in breast cancer patients: association with clinical and pathological parameters","authors":"A.Yu. Kalinchuk, L.A. Tashireva, V.M. Perelmuter","doi":"10.31088/cem2023.12.3.28-40","DOIUrl":"https://doi.org/10.31088/cem2023.12.3.28-40","url":null,"abstract":"Introduction. M1 and M2 macrophages in the tumor microenvironment are known to express programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1). It can determine disease outcomes and tumor response to treatment including immunotherapy. However, the macrophage composition of the breast cancer microenvironment and its relation to various clinical and pathological features have been only partially studied. The aim of the study was to detect the PD-1 and PD-L1 expression features in M1 and M2 macrophages in breast cancer patients depending on menstruation, tumor size, molecular subtype, lymph node metastases, and hematogenous metastases. Materials and methods. The study included 19 patients with breast cancer. Using seven-color multiplex TSA-modified immunohistochemistry, we identified M1 macrophages (CD68+CD163–CD3–CKAE1/3–), M2 macrophages (CD68+/–CD163+CD3–CKAE1/3–), and PD-1 and PD-L1 expression in the macrophages. Results. The macrophage composition of the breast carcinoma microenvironment varies in PD-1 and PD-L1 expression. M1 macrophages are more characteristic to show their expression, and it does not depend on the molecular subtype and the presence of hematogenous metastases. Simultaneously, the relative number of macrophages with phenotypes PD1–PDL1+ M1 and PD1+PDL1+ M2 was higher in patients with tumor size corresponding to T2 compared to T1. Differences in macrophage composition were found in patients depending on the lymph node involvement. Patients without lymph node metastases had virtually no PD-1 expression in M2 macrophages in contrast to patients with them. Conclusion. Breast cancer was shown to have phenotypic variety of macrophages in the tumor microenvironment. Moreover, macrophage composition was diverse in different individuals. Initially, a different composition of macrophages is characteristic of patients with different tumor sizes and different lymph node involvement. Keywords: breast cancer, M1 macrophages, M2 macrophages, PD-L1, PD-1","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135840829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.1.25-32
E. V. Moskvichev, L. M. Merkulova, A. Kuznecova, O. Kostrova, E. G. Drandrova, G. Struchko, E. Speranskaya
Introduction. Breast cancer in women is a very common malignant tumor. The prognosis of the development and management of the disease depend on the clinical stage and biological subtype of the tumor. The aim of the research was to study immunohistochemical characteristics of sentinel lymph nodes in various molecular and biological subtypes of breast cancer. Materials and methods. We studied 44 lymph nodes of females with a diagnosed breast cancer using histological and immunohistochemical methods. Regional axillary lymph nodes without signs of metastatic lesions were taken into the investigation. Hematoxylin and eosin staining was performed; monoclonal antibodies to S100 protein and cluster of lymphocyte differentiation 4 and 8 were used. We used light microscopy to assess the results. Results. We determined molecular and biological subtypes of breast cancer. In 45.5% of cases (n=20) women were diagnosed with luminal cancer (Lum); in 25% of cases (n=11), with Her2+ variant; and in 29.5% of cases (n=13), with Tr– cancer (triple-negative). A more pronounced expression of S100-positive cells was observed in the paracortical zone of lymph nodes in triple-negative compared with the luminal one. We revealed uneven distribution of СD8+ lymphocytes in various subtypes of breast cancer, with an increase in their area in the following sequence: Lum (18.6%), Her2+ (19.8%), and Tr– (20.1%). The lowest number of СD4+ lymphocytes was found in the luminal breast cancer. The largest number of CD4+ cells was observed in the Her2+ subtype. Conclusion. The research demonstrated no reliable differences in the reaction of various sub-populations of T-lymphocytes in early-stage breast cancer. At the same time, we revealed a reliable increase in the number of intrafollicular S100+ cells that indicates dendrite cells activation in Tr– cancer. Keywords: breast cancer, immunohistochemistry, regional lymph node, cellular immunity, lymphocytes
{"title":"Immunohistochemical characteristic of sentinel lymph nodes in various molecular subtypes of breast carcinoma","authors":"E. V. Moskvichev, L. M. Merkulova, A. Kuznecova, O. Kostrova, E. G. Drandrova, G. Struchko, E. Speranskaya","doi":"10.31088/cem2022.11.1.25-32","DOIUrl":"https://doi.org/10.31088/cem2022.11.1.25-32","url":null,"abstract":"Introduction. Breast cancer in women is a very common malignant tumor. The prognosis of the development and management of the disease depend on the clinical stage and biological subtype of the tumor. The aim of the research was to study immunohistochemical characteristics of sentinel lymph nodes in various molecular and biological subtypes of breast cancer. Materials and methods. We studied 44 lymph nodes of females with a diagnosed breast cancer using histological and immunohistochemical methods. Regional axillary lymph nodes without signs of metastatic lesions were taken into the investigation. Hematoxylin and eosin staining was performed; monoclonal antibodies to S100 protein and cluster of lymphocyte differentiation 4 and 8 were used. We used light microscopy to assess the results. Results. We determined molecular and biological subtypes of breast cancer. In 45.5% of cases (n=20) women were diagnosed with luminal cancer (Lum); in 25% of cases (n=11), with Her2+ variant; and in 29.5% of cases (n=13), with Tr– cancer (triple-negative). A more pronounced expression of S100-positive cells was observed in the paracortical zone of lymph nodes in triple-negative compared with the luminal one. We revealed uneven distribution of СD8+ lymphocytes in various subtypes of breast cancer, with an increase in their area in the following sequence: Lum (18.6%), Her2+ (19.8%), and Tr– (20.1%). The lowest number of СD4+ lymphocytes was found in the luminal breast cancer. The largest number of CD4+ cells was observed in the Her2+ subtype. Conclusion. The research demonstrated no reliable differences in the reaction of various sub-populations of T-lymphocytes in early-stage breast cancer. At the same time, we revealed a reliable increase in the number of intrafollicular S100+ cells that indicates dendrite cells activation in Tr– cancer. Keywords: breast cancer, immunohistochemistry, regional lymph node, cellular immunity, lymphocytes","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69280143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.2.22-31
K. A. Artemyeva, E. Goufman, I. Stepanova, N. Tikhonova, M. N. Boltovskaya, E. Ponomarenko, I. M. Bogdanova, M. Mnikhovich, L. Mikhaleva
Introduction. Prostate cancer (PC) leads the world structure of male cancer mortality. Understanding the prognosis for PC patients is vitally important and requires diagnostic enhancements such as developing biomarker panels. The studyaimed to estimate sensitivity, specificity, and prognostic significance of the level of immunoglobulin G (IgG) proteolysis products in the blood serum depending on PC Gleason score and detect how the levels of IgG proteolytic fragments were associated with the diagnostic marker expression. Materials and methods. The study included 90 PC patients. We used the Gleason score to evaluate tumor grade. The level of the IgG proteolysis products and total prostate-specific antigen (PSA) in the serum was detected with ELISA. We performed an immunohistochemical assay with Ki-67, plasminogen-binding protein enolase-1 (ENO-1), and prostate-specific membrane antigen (PSMA). Results. ROC analysis demonstrated 100% specificity of the IgG proteolysis products test regardless of Gleason score, while the sensitivity reached 72.2%, 57.5%, 52.6%, and 46.2% for ISUP stages 1, 2, 3, and 4, respectively. An intergroup comparison showed significant differences between patient groups according to Gleason score, preoperative PSA and IgG proteolysis product serum levels and Ki-67 index. We detected a positive correlation between the level of IgG proteolysis products in the PC patients’ serum and ENO-1 expression and a negative correlation with the Gleason score and PSMA expression. Conclusion. Preoperative detection of high levels of proteolytic IgG fragments in the serum of PC patients even with low Gleason score and PSMA expression may help predict a more aggressive disease course and choose the management strategy. Keywords: prostate cancer, plasminogen activation system, proteolytic fragments of immunoglobulin G, oncomarkers
{"title":"The level of IgG proteolytic fragments as an additional prognostic biomarker of prostate cancer","authors":"K. A. Artemyeva, E. Goufman, I. Stepanova, N. Tikhonova, M. N. Boltovskaya, E. Ponomarenko, I. M. Bogdanova, M. Mnikhovich, L. Mikhaleva","doi":"10.31088/cem2022.11.2.22-31","DOIUrl":"https://doi.org/10.31088/cem2022.11.2.22-31","url":null,"abstract":"Introduction. Prostate cancer (PC) leads the world structure of male cancer mortality. Understanding the prognosis for PC patients is vitally important and requires diagnostic enhancements such as developing biomarker panels. The studyaimed to estimate sensitivity, specificity, and prognostic significance of the level of immunoglobulin G (IgG) proteolysis products in the blood serum depending on PC Gleason score and detect how the levels of IgG proteolytic fragments were associated with the diagnostic marker expression. Materials and methods. The study included 90 PC patients. We used the Gleason score to evaluate tumor grade. The level of the IgG proteolysis products and total prostate-specific antigen (PSA) in the serum was detected with ELISA. We performed an immunohistochemical assay with Ki-67, plasminogen-binding protein enolase-1 (ENO-1), and prostate-specific membrane antigen (PSMA). Results. ROC analysis demonstrated 100% specificity of the IgG proteolysis products test regardless of Gleason score, while the sensitivity reached 72.2%, 57.5%, 52.6%, and 46.2% for ISUP stages 1, 2, 3, and 4, respectively. An intergroup comparison showed significant differences between patient groups according to Gleason score, preoperative PSA and IgG proteolysis product serum levels and Ki-67 index. We detected a positive correlation between the level of IgG proteolysis products in the PC patients’ serum and ENO-1 expression and a negative correlation with the Gleason score and PSMA expression. Conclusion. Preoperative detection of high levels of proteolytic IgG fragments in the serum of PC patients even with low Gleason score and PSMA expression may help predict a more aggressive disease course and choose the management strategy. Keywords: prostate cancer, plasminogen activation system, proteolytic fragments of immunoglobulin G, oncomarkers","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69280372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.3.73-80
V. Smolyannikova, A. Karamova, A. Vorontsova, L. F. Znamenskaya, M. Nefedova, K. M. Aulova
Mycosis fungoides is an epidermotropic primary cutaneous T-cell lymphoma, represented com-posed of small and medium-sized lymphocytes with cerebriform nuclei. Differential diagnosis of cutaneous T-cell lymphoma and chronic autoimmune dermatoses, including psoriasis, may present significant chal-lenges in some cases. We analyzed three clinical cases of mycosis fungoides, in which psoriasis was initially diagnosed. Histological and immunohistochemical studies with a wide panel of antibodies (CD4 CD8, CD2, CD5, CD7, CD3) were performed, and monoclonal T-lymphocyte populations were determined with PCR. We propose an algorithm for diagnosing mycosis fungoides. Keywords: mycosis fungoides, psoriasis, morphology, immunohistochemistrycal study, diagnosis
{"title":"Problems in differential diagnosis of mycosis fungoides and psoriasis: comparison of clinical and morphological features","authors":"V. Smolyannikova, A. Karamova, A. Vorontsova, L. F. Znamenskaya, M. Nefedova, K. M. Aulova","doi":"10.31088/cem2022.11.3.73-80","DOIUrl":"https://doi.org/10.31088/cem2022.11.3.73-80","url":null,"abstract":"Mycosis fungoides is an epidermotropic primary cutaneous T-cell lymphoma, represented com-posed of small and medium-sized lymphocytes with cerebriform nuclei. Differential diagnosis of cutaneous T-cell lymphoma and chronic autoimmune dermatoses, including psoriasis, may present significant chal-lenges in some cases. We analyzed three clinical cases of mycosis fungoides, in which psoriasis was initially diagnosed. Histological and immunohistochemical studies with a wide panel of antibodies (CD4 CD8, CD2, CD5, CD7, CD3) were performed, and monoclonal T-lymphocyte populations were determined with PCR. We propose an algorithm for diagnosing mycosis fungoides. Keywords: mycosis fungoides, psoriasis, morphology, immunohistochemistrycal study, diagnosis","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69281094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2023.12.2.5-13
A. Egorova, D. Voronkov, E. Fedorova, T. I. Baranich, V. Glinkina, V. Sukhorukov
This review considers modern data on the morphology and functions of mitochondria in the neurons and glial cells in various brain structures of laboratory rodents. We discuss the main aspects of intracellular and regional heterogeneity of neuronal mitochondria. The functional differences between mitochondria in different cerebral regions are highlighted. We analyze the structural and functional features of mitochondria in brain gliocytes as well as their role in maintaining glioneuronal interactions. The article presents the latest information on the possibilities of intercellular transportation of mitochondria as a new neuroprotective mechanism illustrated on the functioning of astrocyte-neuron networks. Understanding the structural and functional features of mitochondria in different brain areas may help identify pharmacological targets and develop new strategies for mitochondrial disease management. Keywords: mitochondria, neurons, gliocytes, glio-neuronal interaction
{"title":"Structural and functional features of mitochondria in neurons and gliocytes of various cerebral regions of laboratory rodents","authors":"A. Egorova, D. Voronkov, E. Fedorova, T. I. Baranich, V. Glinkina, V. Sukhorukov","doi":"10.31088/cem2023.12.2.5-13","DOIUrl":"https://doi.org/10.31088/cem2023.12.2.5-13","url":null,"abstract":"This review considers modern data on the morphology and functions of mitochondria in the neurons and glial cells in various brain structures of laboratory rodents. We discuss the main aspects of intracellular and regional heterogeneity of neuronal mitochondria. The functional differences between mitochondria in different cerebral regions are highlighted. We analyze the structural and functional features of mitochondria in brain gliocytes as well as their role in maintaining glioneuronal interactions. The article presents the latest information on the possibilities of intercellular transportation of mitochondria as a new neuroprotective mechanism illustrated on the functioning of astrocyte-neuron networks. Understanding the structural and functional features of mitochondria in different brain areas may help identify pharmacological targets and develop new strategies for mitochondrial disease management. Keywords: mitochondria, neurons, gliocytes, glio-neuronal interaction","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69281331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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