Maria Aparecida Custódio Domingues
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Previous Organizations / Institutes
The organizations / institutes from the scholar's other articles in the past ten years
Research Subjects
Maria Aparecida Custódio Domingues has a total of 376 co-authors. Here are the top co-authors by number of shared publications:
- Silvia Regina Rogatto
Botucatu Medical School Hospital (HCFMB), São Paulo State University—UNESP, Botucatu 18618-687, SP, Brazil
18 shared publications - Cristiano Claudino Oliveira
Department of Pathological Anatomy, A.C.Camargo Cancer Center, São Paulo, SP, Brazil
8 shared publications - Fernando Augusto Soares
Department of Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil
7 shared publications - Norma Sueli Pinheiro Módolo
Department of Surgical Specialties and Anaesthesiology, School of Medicine, São Paulo State University, Botucatu, Brazil
6 shared publications - Elenice Deffune
Medical School, Sao Paulo State University Julio de Mesquita Filho, Botucatu, Brazil
5 shared publications - Ligia Niero-Melo
Faculdade de Medicina de Botucatu da Universidade Estadual Paulista (FMB Unesp), Botucatu, SP, Brazil
5 shared publications
Latest Publications
- Open Access
- 2 December 2025
- Published by Springer Nature in Advances in Rheumatology
- Vol. 66 (1)
Hyperinflammatory status associated with COVID-19: clinical features of a pediatric series
Objective: Explore clinical features, atypical manifestations and rare autoimmune complications of pediatric hyperinflammatory manifestations associated to SARS-CoV-2, observed during the COVID-19 pandemic, and the relationship of Multisystemic Inflammatory Syndrome of Childhood (MIS-C) with other manifestations, such as macrophage activation syndrome, vasculitis and vasculopathy. Methods: A protocol with detailed socio-demographic and clinical features, SARS-CoV-2 exposure and morbidity was conducted in a public tertiary hospital as part of a multicentric international protocol. Cases were selected and enrolled in a single centre from 2020 to 2022, recording all the organ and systems manifestations, standard treatment and outcome. Results: Of the 23 suspicious cases, 21 met the inclusion criteria of MIS-C. Gastrointestinal manifestations were frequent, and three out of 21 had acute abdomen, one with documented histiocytic necrotizing mesenteric lymphadenopathy (Kikuchi-Fujimoto), 3 had macrophage activation syndrome (MAS), and one case, with previous enthesitis related arthritis evolved into type V Takayasu arteritis and malignant hypertension. All patients were treated with either intravenous immunoglobulin (IVIG), high dose glucocorticoids or both, five were under intensive care treatment with respiratory and cardio-circulatory support. All had full recovery during acute phase. Description the lymphonode histopathology showed proliferation of small lymphocytes and macrophage infiltrates with microthrombi and lymph nodes germinal centers necrosis. Conclusion: Post-infectious hyperinflammatory states associated with COVID-19 manifestations may cause not only to transient inflammatory features, but also autoimmunity, vasculitis and vasculopathy manifestations that require prompt treatment.
- 2 December 2025
- Published by Springer Nature in Advances in Rheumatology
- Vol. 66 (1)
Open AccessHyperinflammatory status associated with COVID-19: clinical features of a pediatric series
Objective: Explore clinical features, atypical manifestations and rare autoimmune complications of pediatric hyperinflammatory manifestations associated to SARS-CoV-2, observed during the COVID-19 pandemic, and the relationship of Multisystemic Inflammatory Syndrome of Childhood (MIS-C) with other manifestations, such as macrophage activation syndrome, vasculitis and vasculopathy. Methods: A protocol with detailed socio-demographic and clinical features, SARS-CoV-2 exposure and morbidity was conducted in a public tertiary hospital as part of a multicentric international protocol. Cases were selected and enrolled in a single centre from 2020 to 2022, recording all the organ and systems manifestations, standard treatment and outcome. Results: Of the 23 suspicious cases, 21 met the inclusion criteria of MIS-C. Gastrointestinal manifestations were frequent, and three out of 21 had acute abdomen, one with documented histiocytic necrotizing mesenteric lymphadenopathy (Kikuchi-Fujimoto), 3 had macrophage activation syndrome (MAS), and one case, with previous enthesitis related arthritis evolved into type V Takayasu arteritis and malignant hypertension. All patients were treated with either intravenous immunoglobulin (IVIG), high dose glucocorticoids or both, five were under intensive care treatment with respiratory and cardio-circulatory support. All had full recovery during acute phase. Description the lymphonode histopathology showed proliferation of small lymphocytes and macrophage infiltrates with microthrombi and lymph nodes germinal centers necrosis. Conclusion: Post-infectious hyperinflammatory states associated with COVID-19 manifestations may cause not only to transient inflammatory features, but also autoimmunity, vasculitis and vasculopathy manifestations that require prompt treatment.
- Open Access
- 26 July 2024
- Published by Federação das Associações de Ginecologia e Obstetrícia in Revista Brasileira de Ginecologia e Obstetrícia
- Vol. 46
Association of insulin-like growth factor II mrna-binding protein 3 (IMP3) expression with prognostic and morphological factors in endometrial cancer
Objective Endometrial cancer (EC) is a heterogeneous disease with recurrence rates ranging from 15 to 20%. The discrimination of cases with a worse prognosis aims, in part, to reduce the length of surgical staging in cases with a better prognosis. This study aimed to evaluate the association between Insulin-like growth factor II mRNA-binding protein […] Abstract Objective Endometrial cancer (EC) is a heterogeneous disease with recurrence rates ranging from 15 to 20%. The discrimination of cases with a worse prognosis aims, in part, to reduce the length of surgical staging in cases with a better prognosis. This study aimed to evaluate the association between Insulin-like growth factor II mRNA-binding protein […]
- 26 July 2024
- Published by Federação das Associações de Ginecologia e Obstetrícia in Revista Brasileira de Ginecologia e Obstetrícia
- Vol. 46
Open AccessAssociation of insulin-like growth factor II mrna-binding protein 3 (IMP3) expression with prognostic and morphological factors in endometrial cancer
Objective Endometrial cancer (EC) is a heterogeneous disease with recurrence rates ranging from 15 to 20%. The discrimination of cases with a worse prognosis aims, in part, to reduce the length of surgical staging in cases with a better prognosis. This study aimed to evaluate the association between Insulin-like growth factor II mRNA-binding protein […] Abstract Objective Endometrial cancer (EC) is a heterogeneous disease with recurrence rates ranging from 15 to 20%. The discrimination of cases with a worse prognosis aims, in part, to reduce the length of surgical staging in cases with a better prognosis. This study aimed to evaluate the association between Insulin-like growth factor II mRNA-binding protein […]
- Open Access
- 19 January 2024
- Published by Publicacoes Cientificas de Acesso Aberto e Editora LTDA in Brazilian Journal of Case Reports
- Vol. 4 (4) , 23-33
Bronchiolitis in an infant due to influenza A, necropsy findings: a case report
The influenza virus is an important cause of respiratory disease in infants and presents challenging differential diagnoses to investigate. This is a case report that involves a necroscopic study of a 2-month-old male infant, without previous comorbidities, with a serological diagnosis of influenza A and histopathological presentation of non-obliterating bronchiolitis. Infants are considered a high-risk group for flu complications due to the immaturity of the immune system and the ability to respond to respiratory infections. Furthermore, the severity of infection in infants may be worsened by the difficulty in quickly considering and treating the symptoms of the disease.
- 19 January 2024
- Published by Publicacoes Cientificas de Acesso Aberto e Editora LTDA in Brazilian Journal of Case Reports
- Vol. 4 (4) , 23-33
Open AccessBronchiolitis in an infant due to influenza A, necropsy findings: a case report
The influenza virus is an important cause of respiratory disease in infants and presents challenging differential diagnoses to investigate. This is a case report that involves a necroscopic study of a 2-month-old male infant, without previous comorbidities, with a serological diagnosis of influenza A and histopathological presentation of non-obliterating bronchiolitis. Infants are considered a high-risk group for flu complications due to the immaturity of the immune system and the ability to respond to respiratory infections. Furthermore, the severity of infection in infants may be worsened by the difficulty in quickly considering and treating the symptoms of the disease.
- Open Access
- 1 April 2021
- Published by FapUNIFESP (SciELO) in Avaliação: Revista da Avaliação da Educação Superior (Campinas)
- Vol. 26 (1) , 197-217
Impacto da Política de Reserva de Vagas nas taxas de Evasão na Unesp
A evasão é um tema de interesse mundial na área da educação, contudo o entendimento atual sobre o fenômeno é ainda insuficiente, sobretudo quando o objetivo é avaliar políticas efetivas de evasão. Neste artigo o percentual anual de evasão da Unesp é avaliado com base na adoção da política de reserva de vagas. Existem três possibilidades de ingresso - sistema universal (SU), quota por ter estudado em escola pública (EP) e quota por ser PPI (pretos, pardos, indígenas). Os dados foram segmentados por curso e ano de ingresso. A Unesp tem campus em 24 cidades, que reúnem 34 unidades e abrigam 136 diferentes cursos de Graduação. O ingresso para estes cursos é realizado por meio de vestibular com 186 diferentes opções em 63 carreiras. Uma comparação das taxas de evasão permite observar que elas podem depender do modo de ingresso, mas isso ocorre de forma variada ao longo do tempo e depende da área do curso, não sendo significativo. Verificou-se um decréscimo consistente da taxa de evasão global e por categoria de ingresso.
- 1 April 2021
- Published by FapUNIFESP (SciELO) in Avaliação: Revista da Avaliação da Educação Superior (Campinas)
- Vol. 26 (1) , 197-217
Open AccessImpacto da Política de Reserva de Vagas nas taxas de Evasão na Unesp
A evasão é um tema de interesse mundial na área da educação, contudo o entendimento atual sobre o fenômeno é ainda insuficiente, sobretudo quando o objetivo é avaliar políticas efetivas de evasão. Neste artigo o percentual anual de evasão da Unesp é avaliado com base na adoção da política de reserva de vagas. Existem três possibilidades de ingresso - sistema universal (SU), quota por ter estudado em escola pública (EP) e quota por ser PPI (pretos, pardos, indígenas). Os dados foram segmentados por curso e ano de ingresso. A Unesp tem campus em 24 cidades, que reúnem 34 unidades e abrigam 136 diferentes cursos de Graduação. O ingresso para estes cursos é realizado por meio de vestibular com 186 diferentes opções em 63 carreiras. Uma comparação das taxas de evasão permite observar que elas podem depender do modo de ingresso, mas isso ocorre de forma variada ao longo do tempo e depende da área do curso, não sendo significativo. Verificou-se um decréscimo consistente da taxa de evasão global e por categoria de ingresso.
- Open Access
- 2 December 2020
- Published by Editora e Distribuidora Educacional in Ensaios e Ciência: C. Biológicas, Agrárias e da Saúde
- Vol. 24 (4) , 357-364
Construção com Terra: Breve Histórico e Técnicas
A utilização do solo como matéria prima para técnicas construtivas surgiu junto com a necessidade de os seres humanos se fixarem em locais, construindo as primeiras habitações e sociedades. As primeiras construções em terra crua são datas com mais de 7.000 anos A.C., sendo observado que a utilização desta matéria prima ocorreu em quase todos os continentes devido à diversidade quantidade do material e ao clima. No Brasil, as técnicas construtivas com terra crua foram amplamente utilizadas no período colonial com forte influência dos portugueses que introduziram as técnicas de adobe, taipa de mão e taipa de pilão. Tais técnicas construtivas se mantiveram presentes, mas este modo de construir vem perdendo espaço no final do século VIII e até meados do século XIX e se vê cada vez mais marginalizado. Conhecer estas técnicas construtivas que remontam as civilizações antigas, a sua história e seus métodos e necessário para apreender e entender parte da cultura e das tradições humana. Esta revisão narrativa, baseada em livros, artigos e seminários, faz um levantamento sobre a história da matéria prima solo na construção civil, apresentando cronologicamente as técnicas e métodos construtivos que foram utilizadas em diferentes regiões, com foco nas construções em terra crua conhecidos e usuais no Brasil. Palavras-chave: Construções em Terra. Arquitetura de Terra. Bioconstrução. Abstract The use of soil as raw material for construction techniques arose along with the need for human beings to settle in places, building the first houses and societies. The first constructions on raw earth are dates more than 7,000 years B.C., being observed that the use of this raw material occurred in almost all the continents due to the diversity of the material and the climate. In Brazil, the construction techniques with raw earth were widely used in the colonial period with a strong influence of the Portuguese who introduced the techniques of adobe, rammed earth and rammed earth. Such construction techniques remained present, but this way of building has been losing ground in the late 8th century and until the middle of the 19th century and is increasingly marginalized. Knowing these constructive techniques that go back to ancient civilizations, their history and their methods is necessary to learn and understand part of human culture and traditions. This narrative review, based on books, articles and seminars, surveys the history of soil raw material in civil construction, chronologically presenting the construction techniques and methods that were used in different regions, focusing on the known and usual raw earth constructions in Brazil. Keywords: Earth Constructions. Earth Architecture. Bioconstruction.
- 2 December 2020
- Published by Editora e Distribuidora Educacional in Ensaios e Ciência: C. Biológicas, Agrárias e da Saúde
- Vol. 24 (4) , 357-364
Open AccessConstrução com Terra: Breve Histórico e Técnicas
A utilização do solo como matéria prima para técnicas construtivas surgiu junto com a necessidade de os seres humanos se fixarem em locais, construindo as primeiras habitações e sociedades. As primeiras construções em terra crua são datas com mais de 7.000 anos A.C., sendo observado que a utilização desta matéria prima ocorreu em quase todos os continentes devido à diversidade quantidade do material e ao clima. No Brasil, as técnicas construtivas com terra crua foram amplamente utilizadas no período colonial com forte influência dos portugueses que introduziram as técnicas de adobe, taipa de mão e taipa de pilão. Tais técnicas construtivas se mantiveram presentes, mas este modo de construir vem perdendo espaço no final do século VIII e até meados do século XIX e se vê cada vez mais marginalizado. Conhecer estas técnicas construtivas que remontam as civilizações antigas, a sua história e seus métodos e necessário para apreender e entender parte da cultura e das tradições humana. Esta revisão narrativa, baseada em livros, artigos e seminários, faz um levantamento sobre a história da matéria prima solo na construção civil, apresentando cronologicamente as técnicas e métodos construtivos que foram utilizadas em diferentes regiões, com foco nas construções em terra crua conhecidos e usuais no Brasil. Palavras-chave: Construções em Terra. Arquitetura de Terra. Bioconstrução. Abstract The use of soil as raw material for construction techniques arose along with the need for human beings to settle in places, building the first houses and societies. The first constructions on raw earth are dates more than 7,000 years B.C., being observed that the use of this raw material occurred in almost all the continents due to the diversity of the material and the climate. In Brazil, the construction techniques with raw earth were widely used in the colonial period with a strong influence of the Portuguese who introduced the techniques of adobe, rammed earth and rammed earth. Such construction techniques remained present, but this way of building has been losing ground in the late 8th century and until the middle of the 19th century and is increasingly marginalized. Knowing these constructive techniques that go back to ancient civilizations, their history and their methods is necessary to learn and understand part of human culture and traditions. This narrative review, based on books, articles and seminars, surveys the history of soil raw material in civil construction, chronologically presenting the construction techniques and methods that were used in different regions, focusing on the known and usual raw earth constructions in Brazil. Keywords: Earth Constructions. Earth Architecture. Bioconstruction.
- Open Access
- 1 January 2020
- Published by FapUNIFESP (SciELO) in Acta Cirurgica Brasileira
- Vol. 35 (12) , e351207
Stem cells in end-to-side neurorrhaphy. Experimental study in rats
Purpose: To evaluate the influence of mesenchymal stem cells from adipose tissue in the end-to-side neurorrhaphy, focusing in the nerve regeneration and the muscle reinnervation in acute trauma. Methods: 140 animals were randomly divided in seven groups: control, denervated, end-to-side neurorrhaphy between distal stump of common peroneal nerve and tibial nerve (ESN), ESN wrapped in fascia, ESN wrapped in fascia and platelet gel, ESN wrapped in platelet gel, ESN wrapped in fascia and platelet gel within stem cells (without culture) removed from the adipose tissue. Mass measurements of the animal and of cranial tibial muscles, electromyography, walking track analysis tests and histological examinations of the nerves and muscles after 180 days was performed. Results: In the groups where the ESN was performed, the results were always better when compared to the denervated group, showing reinnervation in all ESN groups. The most sensitive methods were walking track and histological analysis. Only the group with stem cells showed values similar to the control group, as well as the functional indices of peroneal nerve and the number of nerve fibers in the peroneal nerve. Conclusions: Stem cells were effective in ESN according with the functional index of the peroneal nerve, evaluated by walking track analysis and the number of nerve fibers in the peroneal nerve.
- 1 January 2020
- Published by FapUNIFESP (SciELO) in Acta Cirurgica Brasileira
- Vol. 35 (12) , e351207
Open AccessStem cells in end-to-side neurorrhaphy. Experimental study in rats
Purpose: To evaluate the influence of mesenchymal stem cells from adipose tissue in the end-to-side neurorrhaphy, focusing in the nerve regeneration and the muscle reinnervation in acute trauma. Methods: 140 animals were randomly divided in seven groups: control, denervated, end-to-side neurorrhaphy between distal stump of common peroneal nerve and tibial nerve (ESN), ESN wrapped in fascia, ESN wrapped in fascia and platelet gel, ESN wrapped in platelet gel, ESN wrapped in fascia and platelet gel within stem cells (without culture) removed from the adipose tissue. Mass measurements of the animal and of cranial tibial muscles, electromyography, walking track analysis tests and histological examinations of the nerves and muscles after 180 days was performed. Results: In the groups where the ESN was performed, the results were always better when compared to the denervated group, showing reinnervation in all ESN groups. The most sensitive methods were walking track and histological analysis. Only the group with stem cells showed values similar to the control group, as well as the functional indices of peroneal nerve and the number of nerve fibers in the peroneal nerve. Conclusions: Stem cells were effective in ESN according with the functional index of the peroneal nerve, evaluated by walking track analysis and the number of nerve fibers in the peroneal nerve.
- Open Access
- 1 January 2019
- Published by FapUNIFESP (SciELO) in Acta Cirurgica Brasileira
- Vol. 34 (8) , e201900806
Effects of cyclosporine on ischemia-reperfusion injuries in rat kidneys. An experimental model
Key words: Acute Kidney Injury; Cyclosporine; Kidney; Rats, Wistar
- 1 January 2019
- Published by FapUNIFESP (SciELO) in Acta Cirurgica Brasileira
- Vol. 34 (8) , e201900806
Open AccessEffects of cyclosporine on ischemia-reperfusion injuries in rat kidneys. An experimental model
Key words: Acute Kidney Injury; Cyclosporine; Kidney; Rats, Wistar
- Open Access
- 1 September 2018
- Published by Wolters Kluwer Health in Medicine
- Vol. 97 (38) , e12304
Concomitant p53 and PTEN immunoexpression to predict the risk of malignancy in endometrial polyps
The aim of this retrospective cross-sectional study was to assess the usefulness of phosphase and tensin homolog deleted on chromosome 10 (PTEN) and p53 protein immunoexpression in predicting the risk of malignancy in endometrial polyps. The study was conducted at tertiary public hospital, university teaching center, and private practice clinic. A total of 159 patients with endometrial polyps who underwent hysteroscopic polypectomy between January 2010 to December 2014 were included. p53 and PTEN immunoexpression were assessed in histologic endometrial polyp samples. Patients were allocated into 2 groups: group A, endometrial polyps without atypia (120), and group B, endometrial polyps with atypia (39), which were subdivided into A1 (80) and B1 (21) = p53−/PTEN+ immunostaining; A2 (20) and B2 (11) = p53+/PTEN+; A3 (14) and B3 (4) = p53+/PTEN−; A4 (6) and B4 (3) = p53−/PTEN−. There was no significant difference between groups regarding clinical and epidemiologic parameters, except for age. Neoplasia incidence within groups was higher when at least 1 marker was abnormally stained (in group A, P = .0089, odds ratio [OR] = 13.94 [1.62; 120.27]; in group B, P = .0255, OR 12.73 [1.38; 117.27]). Overall neoplasia incidence was higher in group B than in group A (20.5% vs 5.8%; P = .0113). Malignant neoplasia was found more frequently in patients with p53+ (P = .0006, OR = 7.67 [2.30; 25.54]) and PTEN− (P = .0043; OR = 5.43 [1.77; 16.61]). Immunohistochemical analysis using p53 and PTEN as markers, either alone or concomitantly, can be useful to predict malignant transformation in cases of endometrial polyps.
- 1 September 2018
- Published by Wolters Kluwer Health in Medicine
- Vol. 97 (38) , e12304
Open AccessConcomitant p53 and PTEN immunoexpression to predict the risk of malignancy in endometrial polyps
The aim of this retrospective cross-sectional study was to assess the usefulness of phosphase and tensin homolog deleted on chromosome 10 (PTEN) and p53 protein immunoexpression in predicting the risk of malignancy in endometrial polyps. The study was conducted at tertiary public hospital, university teaching center, and private practice clinic. A total of 159 patients with endometrial polyps who underwent hysteroscopic polypectomy between January 2010 to December 2014 were included. p53 and PTEN immunoexpression were assessed in histologic endometrial polyp samples. Patients were allocated into 2 groups: group A, endometrial polyps without atypia (120), and group B, endometrial polyps with atypia (39), which were subdivided into A1 (80) and B1 (21) = p53−/PTEN+ immunostaining; A2 (20) and B2 (11) = p53+/PTEN+; A3 (14) and B3 (4) = p53+/PTEN−; A4 (6) and B4 (3) = p53−/PTEN−. There was no significant difference between groups regarding clinical and epidemiologic parameters, except for age. Neoplasia incidence within groups was higher when at least 1 marker was abnormally stained (in group A, P = .0089, odds ratio [OR] = 13.94 [1.62; 120.27]; in group B, P = .0255, OR 12.73 [1.38; 117.27]). Overall neoplasia incidence was higher in group B than in group A (20.5% vs 5.8%; P = .0113). Malignant neoplasia was found more frequently in patients with p53+ (P = .0006, OR = 7.67 [2.30; 25.54]) and PTEN− (P = .0043; OR = 5.43 [1.77; 16.61]). Immunohistochemical analysis using p53 and PTEN as markers, either alone or concomitantly, can be useful to predict malignant transformation in cases of endometrial polyps.
- Open Access
- 23 August 2018
- Published by Oxford University Press (OUP) in Molecular Human Reproduction
- Vol. 24 (11) , 556-563
MicroRNAs involved in theHMGA2deregulation and its co-occurrence withMED12mutation in uterine leiomyoma
Can the mediator complex subunit 12 (MED12) mutation and high mobility group AT-hook 2 (HMGA2) overexpression co-occurrence be explained by the alternative mechanism of HMGA2 dysregulation in uterine leiomyomas (UL)? The co-occurrence of MED12 mutation and HMGA2 overexpression, and a negative correlation of five validated or predicted microRNAs that target HMGA2 were reported. The recent stratification of UL, according to recurrent and mutually exclusive genomic alterations affecting HMGA2, MED12, fumarate hydratase (FH) and collagen type IV alpha 5–alpha 6 (COL4A5-COL4A6) pointed out the involvement of distinct molecular pathways. However, the mechanisms of regulation involving these drivers are poorly explored. A total of 78 UL and 34 adjacent normal myometrium (NM) tissues was collected from 56 patients who underwent hysterectomies at a single institution. The patients were treated at the Department of Gynecology and Obstetrics, School of Medicine, Sao Paulo State University, Botucatu, SP, Brazil, from October 1995 to February 2004. Gene expression profiling was evaluated from fresh frozen tissues and compared with MED12 mutations at exon 2. In addition, RT-qPCR was applied to evaluate the expression levels of HMGA2 and their predictive miRNA regulators: hsa-let-7a, miR-26a, miR-26b, mir-93 and mir-106b. An unsupervised hierarchical clustering analysis revealed two main clusters with one of them (26 of 42 UL) showing an enrichment of MED12 mutated cases (18 of 26 UL). Increased expression levels of HMGA2 were observed in both clusters, including cases with MED12 mutation (cluster 1:18 UL). A significant HMGA2 overexpression (P < 0.001) in UL in comparison with NM was found. Five miRNAs predicted to regulate HMGA2 were significantly downregulated (P < 0.001) and negatively correlated to HMGA2 expression levels (P < 0.05) in UL. An in vivo functional study was not performed to validate the microRNAs and HMGA2 interaction due to technical limitations. HMGA2 overexpression was detected in a significant number of MED12 mutated ULs, suggesting that these alterations coexist. Furthermore, five miRNAs were described as potential regulators of HMGA2 expression in UL. Data available in the Gene Expression Omnibus GSE42939. This study was supported by grants from Fundação de Amparo a Pesquisa do Estado de São Paulo (# 2008/58835-2) and Conselho Nacional de Pesquisa (# 485032/2007-4), Brazil. The authors declared having no conflicts of interest.
- 23 August 2018
- Published by Oxford University Press (OUP) in Molecular Human Reproduction
- Vol. 24 (11) , 556-563
Open AccessMicroRNAs involved in theHMGA2deregulation and its co-occurrence withMED12mutation in uterine leiomyoma
Can the mediator complex subunit 12 (MED12) mutation and high mobility group AT-hook 2 (HMGA2) overexpression co-occurrence be explained by the alternative mechanism of HMGA2 dysregulation in uterine leiomyomas (UL)? The co-occurrence of MED12 mutation and HMGA2 overexpression, and a negative correlation of five validated or predicted microRNAs that target HMGA2 were reported. The recent stratification of UL, according to recurrent and mutually exclusive genomic alterations affecting HMGA2, MED12, fumarate hydratase (FH) and collagen type IV alpha 5–alpha 6 (COL4A5-COL4A6) pointed out the involvement of distinct molecular pathways. However, the mechanisms of regulation involving these drivers are poorly explored. A total of 78 UL and 34 adjacent normal myometrium (NM) tissues was collected from 56 patients who underwent hysterectomies at a single institution. The patients were treated at the Department of Gynecology and Obstetrics, School of Medicine, Sao Paulo State University, Botucatu, SP, Brazil, from October 1995 to February 2004. Gene expression profiling was evaluated from fresh frozen tissues and compared with MED12 mutations at exon 2. In addition, RT-qPCR was applied to evaluate the expression levels of HMGA2 and their predictive miRNA regulators: hsa-let-7a, miR-26a, miR-26b, mir-93 and mir-106b. An unsupervised hierarchical clustering analysis revealed two main clusters with one of them (26 of 42 UL) showing an enrichment of MED12 mutated cases (18 of 26 UL). Increased expression levels of HMGA2 were observed in both clusters, including cases with MED12 mutation (cluster 1:18 UL). A significant HMGA2 overexpression (P < 0.001) in UL in comparison with NM was found. Five miRNAs predicted to regulate HMGA2 were significantly downregulated (P < 0.001) and negatively correlated to HMGA2 expression levels (P < 0.05) in UL. An in vivo functional study was not performed to validate the microRNAs and HMGA2 interaction due to technical limitations. HMGA2 overexpression was detected in a significant number of MED12 mutated ULs, suggesting that these alterations coexist. Furthermore, five miRNAs were described as potential regulators of HMGA2 expression in UL. Data available in the Gene Expression Omnibus GSE42939. This study was supported by grants from Fundação de Amparo a Pesquisa do Estado de São Paulo (# 2008/58835-2) and Conselho Nacional de Pesquisa (# 485032/2007-4), Brazil. The authors declared having no conflicts of interest.
- Open Access
- 1 July 2018
- Published by Taylor & Francis in OncoTargets and Therapy
- Vol. ume 11, 3949-3958
Immunohistochemical expression of hormone receptors, Ki-67, endoglin (CD105), claudins 3 and 4, MMP -2 and -9 in endometrial polyps and endometrial cancer type I
Objective: The aim of this study was to investigate the malignant potential of endometrial polyps (EP) by assessing the immunoexpressions of both estrogen receptor (ER) and progesterone receptor (PR), Ki-67 cell proliferation index, neovascularization network (endoglin – CD105), cellular adhesion molecules (claudins 3 and 4), and extracellular matrix proteins (MMP-2 and -9) in both EP and endometrioid adenocarcinoma (type I) in comparison with the normal endometrium. Study design: This is a cross-sectional comparative study. Patients were identified from the database of Botucatu Medical School, São Paulo State University (BMS-UNESP) Clinical Pathology Laboratory. Setting: The study was conducted using a convenience sample of patients attending the Sectors of Gynecologic Endoscopy and Family Planning and Gynecologic Oncology of the Department of Gynecology and Obstetrics of BMS-UNESP, Brazil. Patients: A total of 90 women were allocated into the following three groups: EP without atypia (EP, n=30), endometrioid endometrial cancer (EC, n=30), and normal endometrium (control, n=30). Methods: Epidemiological and clinical data were obtained by reviewing medical records. Adenocarcinoma and control cases were assessed using the tissue microarray technique. The immunoexpressions of ER, PR, Ki-67, CD105, claudins 3 and 4, and MMP-2 and -9 were assessed in paraffin blocks containing sections of the largest polyploid lesion fragment and tissue microarray recipient blocks. Major results: Compared to the control group, significant differences in the expression of ER (PPPPPP≥0.05). MMP-2 and -9 expression were nearly absent in all groups. Conclusion: The malignant potential of EP could not be determined through the immunohistochemical parameters used in this study. No MMP-2 or -9 expression was observed in any endometrial tissue sample. Further studies are necessary for a better understanding of the biomolecular mechanisms underlying endometrial carcinogenesis.
- 1 July 2018
- Published by Taylor & Francis in OncoTargets and Therapy
- Vol. ume 11, 3949-3958
Open AccessImmunohistochemical expression of hormone receptors, Ki-67, endoglin (CD105), claudins 3 and 4, MMP -2 and -9 in endometrial polyps and endometrial cancer type I
Objective: The aim of this study was to investigate the malignant potential of endometrial polyps (EP) by assessing the immunoexpressions of both estrogen receptor (ER) and progesterone receptor (PR), Ki-67 cell proliferation index, neovascularization network (endoglin – CD105), cellular adhesion molecules (claudins 3 and 4), and extracellular matrix proteins (MMP-2 and -9) in both EP and endometrioid adenocarcinoma (type I) in comparison with the normal endometrium. Study design: This is a cross-sectional comparative study. Patients were identified from the database of Botucatu Medical School, São Paulo State University (BMS-UNESP) Clinical Pathology Laboratory. Setting: The study was conducted using a convenience sample of patients attending the Sectors of Gynecologic Endoscopy and Family Planning and Gynecologic Oncology of the Department of Gynecology and Obstetrics of BMS-UNESP, Brazil. Patients: A total of 90 women were allocated into the following three groups: EP without atypia (EP, n=30), endometrioid endometrial cancer (EC, n=30), and normal endometrium (control, n=30). Methods: Epidemiological and clinical data were obtained by reviewing medical records. Adenocarcinoma and control cases were assessed using the tissue microarray technique. The immunoexpressions of ER, PR, Ki-67, CD105, claudins 3 and 4, and MMP-2 and -9 were assessed in paraffin blocks containing sections of the largest polyploid lesion fragment and tissue microarray recipient blocks. Major results: Compared to the control group, significant differences in the expression of ER (PPPPPP≥0.05). MMP-2 and -9 expression were nearly absent in all groups. Conclusion: The malignant potential of EP could not be determined through the immunohistochemical parameters used in this study. No MMP-2 or -9 expression was observed in any endometrial tissue sample. Further studies are necessary for a better understanding of the biomolecular mechanisms underlying endometrial carcinogenesis.