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1.
Nat Commun ; 15(1): 1302, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383522

RESUMO

The interactions between tumor and immune cells along the course of breast cancer progression remain largely unknown. Here, we extensively characterize multiple sequential and parallel multiregion tumor and blood specimens of an index patient and a cohort of metastatic triple-negative breast cancers. We demonstrate that a continuous increase in tumor genomic heterogeneity and distinct molecular clocks correlated with resistance to treatment, eventually allowing tumors to escape from immune control. TCR repertoire loses diversity over time, leading to convergent evolution as breast cancer progresses. Although mixed populations of effector memory and cytotoxic single T cells coexist in the peripheral blood, defects in the antigen presentation machinery coupled with subdued T cell recruitment into metastases are observed, indicating a potent immune avoidance microenvironment not compatible with an effective antitumor response in lethal metastatic disease. Our results demonstrate that the immune responses against cancer are not static, but rather follow dynamic processes that match cancer genomic progression, illustrating the complex nature of tumor and immune cell interactions.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Genômica/métodos , Microambiente Tumoral
2.
Rev. senol. patol. mamar. (Ed. impr.) ; 36(3)jul.- sep. 2023. tab, ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-223883

RESUMO

Introducción: el carcinoma micropapilar infiltrante (CMI) es una variante histológica inusual y potencialmente agresiva caracterizada por primera vez en 1993 por Siriangkul et al. y que no formó parte de la clasificación de la Organización Mundial de la Salud (OMS) hasta 2003, como tumor mamario epitelial. Representa menos del 2% del total de carcinomas invasivos de la mama y se presupone que presenta un pronóstico desfavorable en comparación con otros carcinomas convencionales debido a su elevado tropismo vascular y linfático. Material y métodos: hasta la fecha no existe ningún estudio con un número elevado de pacientes procedentes de un único centro (> 100 casos) con un periodo de seguimiento largo (> 20 años) que compare la supervivencia del CMI con otros carcinomas convencionales no micropapilares. Se ha llevado a cabo un estudio retrospectivo, observacional con un total de 401 pacientes: 174 con CMI y 227 con otros carcinomas convencionales. Resultados: el CMI presenta mayor grado histológico, mayor afectación ganglionar y mayor riesgo de metástasis a distancia en comparación con otros carcinomas convencionales de características similares. Sin embargo, en el análisis multivariante considerando factores pronósticos como edad, tamaño tumoral, afectación ganglionar y grado histológico, no se observan diferencias estadísticamente significativas para la supervivencia global y libre de enfermedad entre los CMI diagnosticados en el mismo periodo de tiempo que los casos pareados del grupo control y otros carcinomas convencionales. Conclusión: la supervivencia global y libre de enfermedad es similar entre el CMI y otros carcinomas convencionales a igual edad, tamaño tumoral, grado histológico y afectación ganglionar. (AU)


Introduction: Invasive Micropapillary Carcinoma of the breast (IMPC) is an unusual and aggressive histological variant characterized for the first time in 1993 by Siriangkul et al. and classified by the World Health Organization in 2003 as an epithelial breast tumor. It represents less than 2% of all invasive carcinomas of the breast and is presumed to have an unfavorable prognosis compared to other conventional carcinomas due to its high vascular and lymphatic tropism. Material and methods: Until now, there is no study with a large number of patients from a single center with a long follow-up period that compares the survival of IMPC with other conventional non-micropapillary carcinomas. A retrospective, observational study has been carried out with a total of 401 patients: 174 with IMPC and 227 with other conventional carcinomas. Results: IMPC has a higher histological grade, greater lymph node involvement and a higher risk of distant metastasis compared to other conventional carcinomas. However, in the multivariate analysis considering date of diagnosis, age, tumor size, lymph node involvement and histological grade as variables, no statistically significant differences were observed for overall and disease- free survival between IMPC and other conventional carcinomas. Conclusion: Overall and disease-free survival is similar between IMPC and other conventional carcinomas considering same age, tumor size, histological grade, and lymph node involvement. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma Papilar/diagnóstico , Sobrevivência , Estudos Retrospectivos , Estudos Longitudinais , Espanha
3.
J Clin Pathol ; 76(1): 47-52, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34429353

RESUMO

AIMS: Gene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated. METHODS: Cell lines harbouring EML4(13)-ALK(20) and SLC34A2(4)-ROS1(32) gene fusions were adopted to prepare reference standards. Eight laboratories (five adopting amplicon-based and three hybridisation-based platforms) received, at different dilution points two sets of slides (slide A 50.0%, slide B 25.0%, slide C 12.5% and slide D wild type) stained by Papanicolaou (Pap) and May Grunwald Giemsa (MGG). Analysis was carried out on a total of 64 slides. RESULTS: Four (50.0%) out of eight laboratories reported results on all slides and dilution points. While 12 (37.5%) out of 32 MGG slides were inadequate, 27 (84.4%) out of 32 Pap slides produced libraries adequate for variant calling. The laboratories using hybridisation-based platforms showed the highest rate of inadequate results (13/24 slides, 54.2%). Conversely, only 10.0% (4/40 slides) of inadequate results were reported by laboratories adopting amplicon-based platforms. CONCLUSIONS: Reference standards in cytological format yield better results when Pap staining and processed by amplicon-based assays. Further investigation is required to optimise these standards for MGG stained cells and for hybridisation-based approaches.


Assuntos
Neoplasias , Proteínas de Fusão Oncogênica , Humanos , Padrões de Referência , Coloração e Rotulagem
4.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362082

RESUMO

Soemmerring's rings consist of a ring of lens epithelial derived cells that grow along the periphery of an aphakic lens capsule, or around an intraocular lens. These rings when visualized frontally, appear opaque, however, in some cases the cells that compose these rings are organized in the same fashion as those in normal transparent adult lenses. Thus, our purpose was to test whether any part of the adult Soemmerring's ring could be transparent and how this related to morphological factors. To study this, 16 Soemmerring's rings were extracted from donor eye globes. After imaging, they were thickly sectioned sagittally in order to analyze the degrees of transparency of different areas. All samples were also histologically analyzed using alpha smooth muscle actin, Vimentin, wheat germ agglutinin and DAPI. Our results showed that many samples had some transparent areas, mostly towards the center of their cross-section. Of the factors that we analyzed, only lens fiber organization at the bow region and an increased area of mature lens fiber cells had a significant relation to the degree of transparency at the center. Thus, we can conclude that as Soemmerring's rings mature, they can develop organized and transparent areas of lens cells.


Assuntos
Cápsula do Cristalino , Cristalino , Lentes Intraoculares , Humanos , Epitélio
5.
Rev. esp. patol ; 55(4): 240-244, Oct-Dic. 2022. ilus
Artigo em Inglês | IBECS | ID: ibc-210612

RESUMO

Organoid (hypermature) teratomas are highly specialized teratomas showing organ formation, most frequently from the digestive tract or bronchial wall. We present four cases of ovarian organoid teratomas, one with a distinguishable mandible with teeth, one with small intestine, one with large intestine containing a well differentiated neuroendocrine tumor and another with both large intestine and bronchial wall. These tumors have a distribution similar to conventional teratomas and usually behave benignly, although cases of malignancy have been reported.(AU)


Los teratomas hipermaduros u organoides son teratomas altamente especializados en los que existe formación de órganos. Los más comunes son del tracto digestivo y de la pared bronquial. Presentamos cuatro casos de teratomas organoides del ovario: uno con formación de mandíbula con estructuras dentales, otro con intestino delgado, otro con intestino grueso con un tumor neuroendocrino bien diferenciado, y otro intestino grueso y pared bronquial. Estos tumores son de comportamiento benigno, aunque se han descrito casos con malignización. Pueden ocurrir en cualquier lugar donde se localicen los teratomas convencionales.(AU)


Assuntos
Humanos , Feminino , Adulto Jovem , Adulto , Teratoma/diagnóstico por imagem , Organoides , Ovário , Tumores Neuroendócrinos , Pacientes Internados , Exame Físico , Avaliação de Sintomas , Intestino Grosso , Intestino Delgado , Patologia , Serviço Hospitalar de Patologia
6.
Rev Esp Patol ; 55(4): 240-244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36154730

RESUMO

Organoid (hypermature) teratomas are highly specialized teratomas showing organ formation, most frequently from the digestive tract or bronchial wall. We present four cases of ovarian organoid teratomas, one with a distinguishable mandible with teeth, one with small intestine, one with large intestine containing a well differentiated neuroendocrine tumor and another with both large intestine and bronchial wall. These tumors have a distribution similar to conventional teratomas and usually behave benignly, although cases of malignancy have been reported.


Assuntos
Tumores Neuroendócrinos , Neoplasias Ovarianas , Teratoma , Feminino , Humanos , Organoides/patologia , Neoplasias Ovarianas/patologia , Teratoma/patologia
7.
Eur J Obstet Gynecol Reprod Biol ; 265: 181-189, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34509877

RESUMO

OBJECTIVE: To provide a description of laparoscopic myomectomy and the two hemostatic techniques performed over the last 11 years in a single reference center for gynecology and obstetrics and to evaluate the factors associated with favorable surgical outcomes. STUDY DESIGN: We retrospectively analyzed 625 who underwent laparoscopic myomectomy from January 2009 to December 2019. RESULTS: Of 625 patients, 437 (69.8%) were symptomatic. The most common symptoms were heavy uterine bleeding (33.2%). 188 patients (30.1%) were asymptomatic but were operated in 77 cases (12.3%) for rapid fibroid growth, 32 (5.1%) for uterine cavity distortion and, in 45 cases (8.6%), the myomectomy was indicated during a surgery for other medical reason due to its accessibility. In 173 cases (27.9%) intramyometrial adrenaline was injected and in 246 cases (39.7%) a temporary blockage of the uterus blood supply was performed. Only 35 (5.6%) patients presented complications, of which, 14 (40%) were hemorrhagic. These hemorrhagic complications were more frequent when intramyometrial adrenaline was used (5,8%) than after the temporary clipping of the uterine arteries and infundibulopelvic ligaments (0,8%; p < 0,001). In the multivariate logistic regression model, the only factor statistically associated with favorable surgical outcome was the use of temporary clipping of the uterine arteries at their origin and infundibulopelvic ligaments as hemostatic technique during the surgery. CONCLUSION: Laparoscopic myomectomy was generally safe with a high level of favorable outcomes. The temporary clipping of uterine arteries and infundibulopelvic ligaments presented fewer intraoperative bleedings compared with injecting intramyometrial adrenaline.


Assuntos
Ginecologia , Laparoscopia , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Técnicas Hemostáticas , Humanos , Gravidez , Estudos Retrospectivos , Miomectomia Uterina/efeitos adversos , Neoplasias Uterinas/cirurgia
8.
Rev Esp Patol ; 54(4): 242-249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34544554

RESUMO

Adenoid cystic carcinoma of the breast (ACCB) is a rare triple negative tumor (TNT) with an excellent prognosis in most cases. Three different histologic types are recognized: classic ACCB, solid basaloid ACCB (SB-ACCB), and ACCB with high-grade transformation. A majority of these tumors show characteristic molecular and immunohistochemical (IHC) features, with fusion of MYB and NFIB genes and overexpression of MYB, respectively. Basaloid carcinomas of the breast (BCB) are infrequently described. They resemble SB-ACCB and TNT of no special type (TNT-NST). We have studied the clinicopathological features of 17 ACCB and 9 BCB, investigating the expression of MYB by IHC and the rearrangements of MYB by fluorescence in situ hybridization (FISH). MYB was expressed by IHC in 15 ACCB and in 3 BCB. MYB FISH detected rearrangements in 11 ACCB and in 2 BCB. After a mean follow-up of 90 months, with a range of 12-204 months, 2 patients with ACCB with high-grade transformation and 1 patient with BCB developed metastases and died of disease. In summary, most ACCB have a good prognosis, but tumors with adverse histopathological features may metastasize. BCB may overlap with ACCB and TNT-NST, and their prognosis should be further studied.


Assuntos
Neoplasias da Mama , Carcinoma Adenoide Cístico , Mama , Carcinoma Adenoide Cístico/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Prognóstico
9.
Case Rep Oncol ; 14(2): 1144-1151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413746

RESUMO

Vulvar malignant melanoma is the second most common subtype of vulvar cancer, accounting for 5-10% of all vulvar cancers. The prognosis is still very poor, although some advances have been achieved in the last years. One of the most significant changes in its management has been the development of less invasive surgical techniques that diminish the risk of postoperative morbidity and long-lasting sequelae. In this article, we review the surgical management of the pathology, based on the comment of 3 cases with vulvar melanoma treated at our institution.

10.
Rev. senol. patol. mamar. (Ed. impr.) ; 33(3): 94-103, jul.-sept. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-197292

RESUMO

La Sociedad Española de Senología y Patología Mamaria, a través de un grupo de expertos, ha redactado la vía clínica de cáncer de mama que constituye una importante herramienta de mejora continua en la atención de la paciente. Consta de 2 matrices temporales, una de diagnóstico y otra de tratamiento, en las que se describen todos los aspectos relacionados con el diagnóstico y el tratamiento del cáncer de mama desde el punto de vista de las distintas especialidades, teniendo en cuenta la distribución temporal de los mismos. Acompañan a estas matrices toda una serie de tablas y documentos explicativos de cada fase. Además, incluye un listado de indicadores para la validación de los distintos procesos. El documento completo se publicará como una monografía de forma inminente y se distribuirá a todos los socios y a los especialistas relacionados con el manejo de la paciente con cáncer de mama


The Spanish Society of Senology and Breast Disease, through a group of experts, has drawn up a clinical pathway for breast cancer, which constitutes an important tool for continuous quality assurance in patient care. The pathway consists of 2 temporary matrices, one for diagnosis and the other for treatment, in which all aspects related to the diagnosis and treatment of breast cancer are described from the point of view of the different specialties, taking into account their temporal distribution. These matrices are accompanied by tables and explanatory documents for each phase. The document also includes a list of indicators for the validation of the different processes. The complete document will be published as a monograph in the near future and will be distributed to all members and specialists involved in the management of breast cancer patients


Assuntos
Humanos , Procedimentos Clínicos/organização & administração , Neoplasias da Mama , Equipe de Assistência ao Paciente/organização & administração , Guias de Prática Clínica como Assunto , Colaboração Intersetorial , Publicações , Unidades Hospitalares/organização & administração , Avaliação de Processos e Resultados em Cuidados de Saúde
11.
Rev. senol. patol. mamar. (Ed. impr.) ; 33(1): 3-8, ene.-mar. 2020. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-193240

RESUMO

OBJETIVO: Evaluar el rendimiento de la biopsia por punción (BPP) en el diagnóstico de tumor filodes (TF) de la mama. MATERIAL Y MÉTODOS: Se han revisado todos los diagnósticos anatomopatológicos de TF emitidos tanto en BPP como en biopsia quirúrgica (BQ). Se analizan las características clínicas, de imagen y patológicas de los casos y la concordancia diagnóstica entre la BPP y la BQ. RESULTADO: Se han estudiado un total de 87 casos con diagnóstico de TF, 16 en BPP y 71 en BQ. En 18 casos se dispuso de BPP y BQ. Los TFB diagnosticados en BPP fueron: 7 FAD (uno de ellos de la variedad celular), 2 TFB, un TFL, 2TFM y un hamartoma. Dos casos de TFB en BQ habían sido diagnosticados respectivamente en la BPP de fibrosis e hiperplasia. Un TFM en BPP resultó ser un TFL en la BQ. Hubo concordancia diagnóstica en un TFL y un TFM. Se detectaron 5 (27%) falsos negativos y 8 falsos positivos (38%). CONCLUSIONES: El rendimiento de la BPP en el diagnóstico de los TF es bajo con una alta tasa de falsos negativos y falsos positivos. Por ello se aconseja emitir un diagnóstico en la BPP de lesión fibroepitelial con estroma celular dejando pendiente un diagnóstico definitivo a disponer de la BQ


OBJECTIVE: To evaluate the role of core needle biopsy (CNB) in the diagnosis of phyllodes tumour (PT) of the breast. MATERIAL AND METHODS: All pathological diagnoses of PT in both CNB and surgical biopsy (SB) were reviewed. The clinical, imaging and pathological characteristics of the cases and the diagnostic agreement between CNB and SB were analysed. RESULT: A total of 87 cases with a diagnosis of PT, 16 in CNB and 71 in SB, were studied. In 18 cases, CNB and SB were available. Benign PT diagnosed in CNB consisted of: 7 fibroadenomas (one of them cellular), 2 benign PT, 1 borderline PT, 2 malignant PT, and 1 hamartoma. Two cases of benign PT in SB had been diagnosed with CNB as fibrosis and hyperplasia. One PT diagnosed as malignant in CNB was diagnosed as a borderline PT in SB. There was diagnostic agreement in 1 borderline PT and 1 malignant PT. We detected 5 (27%) false negatives and 8 false positives (38%). CONCLUSIONS: The efficiency of CNB in the diagnosis of PT is low, with a high rate of false negatives and false positives. Therefore, it is advisable to suggest a diagnosis of fibroepithelial lesion with cellular stroma in CNB, reserving definitive diagnosis to SB


Assuntos
Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Biópsia por Agulha/métodos , Neoplasias da Mama/patologia , Tumor Filoide/patologia , Reações Falso-Negativas , Reações Falso-Positivas
12.
Int J Cancer ; 147(1): 277-284, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31953839

RESUMO

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Although most patients are diagnosed at early stages, 15-20% will relapse despite local treatment. Presently, there are no reliable markers to identify patients with worse outcomes who may benefit from adjuvant treatments, such as chemotherapy, and liquid biopsies may be of use in this setting. Peritoneal lavages are systematically performed during endometrial surgery but little data are available about their potential as liquid biopsies. We analyzed KRAS and PIK3CA mutations in paired surgical biopsies, blood and cytology-negative peritoneal lavages in a cohort of 50 EC patients. Surgical biopsies were submitted to next-generation sequencing (NGS) while circulating-free DNA (cfDNA) purified from plasma and peritoneal lavages was analyzed for KRAS and PIK3CA hotspot mutations using a sensitive quantitative polymerase chain reaction (PCR) assay. NGS of biopsies revealed KRAS, PIK3CA or concomitant KRAS + PIK3CA mutations in 33/50 (66%) EC patients. Of those, 19 cases carried hotspot mutations. Quantitative PCR revealed KRAS and/or PIK3CA mutations in the lavages of 9/19 (47.4%) hotspot EC patients. In contrast, only 2/19 (10.5%) blood samples from hotspot EC patients were positive. Mutations found in cfDNA consistently matched those in paired biopsies. One of the two patients positive in plasma and lavage died in less than 6 months. In conclusion, mutational analysis in peritoneal lavages and blood from early stage EC is feasible. Further studies are warranted to determine if it might help to identify patients with worse prognosis. Human genes discussed: KRAS, KRAS proto-oncogene, GTPase; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.


Assuntos
Neoplasias do Endométrio/genética , Mutação , Idoso , Idoso de 80 Anos ou mais , Alelos , Classe I de Fosfatidilinositol 3-Quinases/genética , Análise Mutacional de DNA , DNA Circular/sangue , DNA Circular/genética , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida , Pessoa de Meia-Idade , Lavagem Peritoneal/métodos , Estudo de Prova de Conceito , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas p21(ras)/genética , Reação em Cadeia da Polimerase em Tempo Real
13.
Saudi J Ophthalmol ; 34(4): 319-323, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-34527883

RESUMO

A 70-year-old male presented with orbital masses affecting the muscular cone. His past medical history was notable for diabetes mellitus, ischemic cardiopathy, sleep-apnea syndrome, and multiple serous effusions. The first biopsy specimen of affected orbital tissue revealed fibrohistiocytic infiltration resembling xanthogranuloma or Erdheim-Chester disease (ECD). An ulterior biopsy of affected orbital tissue showed lymphocyte emperipolesis with immunopositivity for CD68 and S100 but negative staining for CD1a marker, strongly suggesting Rosai-Dorfman disease (RDD). Afterward, pericardium and peritoneal effusions resulted in constrictive pericarditis and retroperitoneal fibrosis, respectively. The absence of distinctive clinical features made the diagnosis especially challenging. Attempts to control the disease using corticosteroids, radiation, orbital surgery, and interferon were unsuccessful. Aggressive treatments such as chemotherapy were not considered appropriate due to the general deterioration of our patient. Although the possibility of two concurrent diseases (e.g., systemic ECD and orbital RDD) cannot be discarded, we interpreted the orbital findings as likely due to RDD, and the entire condition of our patient as an extranodal RDD with atypical clinicopathological findings and outcome.

14.
Breast Cancer Res Treat ; 179(3): 755-762, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31776828

RESUMO

OBJECTIVE: Mammographic breast density (BDen), the ratio of glandular volume (GVol) to breast volume (BVol), is the second most prevalent risk factor for breast cancer (BC). Newly developed photon counting technology allows precise and systematic measurements in clinical practice. Our objective is to see how these parameters change with age in women with and without cancer. MATERIALS AND METHODS: This retrospective study analyzed results of BDen, GVol, and BVol in 64,182 mammograms performed with photon counting technology on 32,448 consecutive women from April 2014 to December 2015. Only their first study was included. We excluded women with incomplete data or with breast implants. RESULTS: Mean age of women without BC diagnosed during the study period was 52.1 ± 9.9. BC and was found in 263 women (0.81%). Mean age was 53.0 ± 10.4. BDen, GVol, and BVol were 14%, 24%, and 2% greater in women with BC (P < 0.001 for BDen and GVol and P = 0.02 for BVol). BDen and GVol diminished following similar patterns across age in both groups, with soft slopes before and after a steep drop from 50 to 60, probably due to menopause. CONCLUSION: BDen diminishes with age in women with or without BC, but it is generally higher in women with BC. GVol could be a more robust indicator associated with BC risk than BDen. This technology can ease the way to studies of interventions to diminish BDen (or GVol) in the hope of diminishing BC incidence or predict if longitudinal changes are indicative of impending cancer.


Assuntos
Densidade da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Glândulas Mamárias Humanas/diagnóstico por imagem , Glândulas Mamárias Humanas/patologia , Mamografia , Absorciometria de Fóton/métodos , Absorciometria de Fóton/normas , Adulto , Idoso , Neoplasias da Mama/terapia , Estudos Transversais , Análise de Dados , Feminino , Humanos , Mamografia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Tumoral
15.
Int J Mol Sci ; 20(22)2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31698766

RESUMO

Endometriosis is a prevalent disease defined by the presence of endometrial tissue outside the uterus. Adenosine triphosphate (ATP), as a proinflammatory molecule, promotes and helps maintain the inflammatory state of endometriosis. Moreover, ATP has a direct influence on the two main symptoms of endometriosis: infertility and pain. Purinergic signaling, the group of biological responses to extracellular nucleotides such as ATP and nucleosides such as adenosine, is involved in the biology of reproduction and is impaired in pathologies with an inflammatory component such as endometriosis. We have previously demonstrated that ectonucleotidases, the enzymes regulating extracellular ATP levels, are active in non-pathological endometria, with hormone-dependent changes in expression throughout the cycle. In the present study we have focused on the expression of ectonucleotidases by means of immunohistochemistry and in situ activity in eutopic and ectopic endometrial tissue of women with endometriosis, and we compared the results with endometria of women without the disease. We have demonstrated that the axis CD39-CD73 is altered in endometriosis, with loss of CD39 and CD73 expression in deep infiltrating endometriosis, the most severe, and most recurring, endometriosis subtype. Our results indicate that this altered expression of ectonucleotidases in endometriosis boosts ATP accumulation in the tissue microenvironment. An important finding is the identification of the nucleotide pyrophophatase/phosphodiesterase 3 (NPP3) as a new histopathological marker of the disease since we have demonstrated its expression in the stroma only in endometriosis, in both eutopic and ectopic tissue. Therefore, targeting the proteins directly involved in ATP breakdown could be an appropriate approach to consider in the treatment of endometriosis.


Assuntos
Trifosfato de Adenosina/metabolismo , Coristoma/enzimologia , Endometriose/enzimologia , Endométrio/enzimologia , Endométrio/patologia , Nucleotidases/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade
16.
Gynecol Endocrinol ; 35(11): 991-994, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31109208

RESUMO

A retrospective observational study to assess whether hormonal treatment (HT) with transdermal estrogens alone or in combination with micronized progesterone increases breast density and to compare these changes to those of a control group of 4120 patients were not given HT. We included 150 patients whose baseline breast density was assessed with photon-counting spectral mammography and 1 year after hormone treatment. The reduction in breast density was compared using an analysis of covariance. The difference in breast density between mammographies in the HT group was -0.40 ± 5.5 and -0.85 ± 4.2 in the control group. The changes in density according to the type of HT, we found that women on treatment with estrogen alone presented a difference of 0.44 ± 5.8, and -1.35 ± 5 (p = 0.13) in women on combined treatment. After adjusting changes in density for age and average number of days between mammographies, we observed a difference of -0.36 95% confidence intervals (CI) [-1.04 to -0.31] in the women on HT and -0.71 95% CI [-1.65 to -0.21] in the control group. No increased breast density was observed in women on HT treatment, nor did we observe an increase according to HT type. The difference in breast density loss was smaller in the HT group versus the control group.


Assuntos
Densidade da Mama/efeitos dos fármacos , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Progesterona/administração & dosagem , Administração Cutânea , Administração Intravaginal , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Oncotarget ; 9(5): 6028-6041, 2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29464052

RESUMO

Microenvironmental properties are thought to be responsible for feto-maternal tolerance. Speculatively, ectopic expression of placental gene programs might also be related to cancer cells' ability to escape from immune vigilance mechanisms during carcinogenesis and cancer progression. Recently, we published the first human genomic evidence of similar immune related gene expression profiles in both placenta (placenta and decidual tissue) and cancer (both primary and metastatic) in the same patient with lymph-node positive breast carcinoma during pregnancy. Here we report the first epigenomic analysis of these tissue samples and describe their main findings, with respect to immune related genes regulation (over or under expressed) in cancer cells with regards placental tissues. We confirm significant similarities, and hierarchical clustering (both unsupervised and supervised), in CpG island methylation patterns between decidual/placental and cancer microenvironments, which cannot be easily explained by simple models or unique pathways. Several different cell types are probably involved in these complex immune regulation mechanisms. Cancers may somehow "hijack" gene programs evolved over millions of years to allow for feto-maternal tolerance in placental mammals in order to escape from immune vigilance and spread locally or to distant sites.

18.
J Hip Preserv Surg ; 4(1): 74-79, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28630724

RESUMO

This description shows the histological findings of a peroneus brevis tendon allograft used for labral reconstruction, implanted 8 weeks before being retrieved due to a postoperative complication unrelated to the graft. As far as we have knowledge this is the first description about revascularization of an allograft used for hip labral reconstruction. The histological report of the removed peroneus brevis tendon allograft shows evidence of vascular ingrowth represented by small vessels with a thin muscular wall in all layers of the graft and cellular migration mainly represented by mature fibroblasts.

19.
Rev. senol. patol. mamar. (Ed. impr.) ; 30(2): 45-51, abr.-jun. 2017. tab
Artigo em Espanhol | IBECS | ID: ibc-163544

RESUMO

Objetivo. Establecer el estado actual de las unidades de patología mamaria (UPM) en la utilización de indicadores de calidad del manejo del cáncer de mama. Material y métodos. Se efectuó una búsqueda bibliográfica de indicadores del manejo del cáncer de mama. Con los resultados se confeccionó una encuesta electrónica de 27 preguntas que se envió a 167 UPM censadas en el Grupo de Estudios Senológicos. Se consideraron las respuestas de 33 de las UPM. Resultados. Solo 9 de las UPM que respondieron estaban acreditadas por la SESPM. Los indicadores más utilizados fueron: utilización de informes siguiendo guías estandarizadas en diagnóstico por la imagen, pacientes con cáncer orientadas para tratamiento por un comité multidisciplinar, determinación de factores pronósticos y predictivos en carcinoma infiltrante, y especificación en el informe de la distancia al margen más cercano de la lesión. Por grupos de indicadores los más utilizados fueron los del procedimiento general y anatomía patológica. Las UPM acreditadas utilizan los indicadores con mayor frecuencia que las no acreditadas. Solo 8 de los 20 indicadores eran utilizados por más del 70% de las UPM para el control de calidad de la unidad y no solo del servicio que los origina. Conclusión. El uso de indicadores para el control de calidad es una herramienta ampliamente utilizada en las UPM que han contestado la encuesta, si bien en muchas ocasiones el indicador solo se usa en el servicio que lo origina y no para la evaluación del funcionamiento de la unidad de forma integral (AU)


Objective. To determine the current state of breast pathology units (BPU) in the use of quality indicators in breast cancer management. Material and methods. After a literature research of breast cancer management indicators, a 27-question survey was designed and sent on-line to 167 BPU from the Group for Senology Studies. Completed surveys were considered from 33 BPU. Results. Only 9 of the BPU that responded were accredited by the SESPM. The most commonly used indicators were the following: use of standardised reporting guidelines in imaging diagnosis, patients with breast cancer treated by a multidisciplinary committee, determination of prognostic and predictive factors in invasive carcinoma, and specification of margin distance in the pathologic report. The most widely used indicators were those of the general process and pathology. Use of the indicators was more frequent in accredited than in non-accredited BPU. Only 8 of the 20 indicators were used by more than 70% of BPU for unit quality control and not only by the service creating them. Conclusions. The use of indicators for quality control is a widely used tool in the BPU responding to the survey. However, indicators are often only used in the service creating them and not for integral quality assessment of the BPU (AU)


Assuntos
Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Indicadores de Qualidade em Assistência à Saúde/organização & administração , Controle de Qualidade , Carcinoma in Situ/epidemiologia , Carcinoma Ductal de Mama/epidemiologia , Indicadores de Qualidade em Assistência à Saúde/normas , Indicadores de Qualidade em Assistência à Saúde , Inquéritos e Questionários
20.
Oncotarget ; 7(50): 83817-83827, 2016 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-27852037

RESUMO

The hypothesis of this work is that, in order to escape the natural immune surveillance mechanisms, cancer cells and the surrounding microenvironment might express ectopically genes that are physiologically present in the placenta to mediate fetal immune-tolerance. These natural "placental immune-editing switch" mechanisms (PIES) may represent the result of millions of years of mammalian evolution developed to allow materno-fetal tolerance. Here, we introduce genes of the immune regulatory pathways that are either similarly over- or under-expressed in tumor vs normal tissue. Our analysis was carried out in primary breast cancer with metastatic homolateral axillary lymph nodes as well as placenta tissue (both uterine decidual tissue and term placenta tissue) from a pregnant woman. Gene expression profiling of paired non-self and self tissues (i.e. placenta/uterus; breast cancer/normal breast tissue; metastatic lymphnode/normal lymphnode tissue) was performed using the PanCancer Immune gene panel, a 770 Nanostring gene expression panel. Our findings reveal overlapping in specific immune gene expression in placenta and cancer tissue, suggesting that these genes might play an important role in maintaining immune tolerance both physiologically (in the placenta) and pathologically (in the cancer setting).


Assuntos
Neoplasias da Mama/imunologia , Carcinoma Lobular/imunologia , Tolerância Imunológica , Placenta/imunologia , Complicações na Gravidez/imunologia , Evasão Tumoral , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Lobular/genética , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Tolerância Imunológica/genética , Imuno-Histoquímica , Metástase Linfática , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/patologia , Complicações na Gravidez/cirurgia , Evasão Tumoral/genética , Microambiente Tumoral
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