RESUMO
HuR regulates cytoplasmic mRNA stability and translatability, with its expression correlating with adverse outcomes in various cancers. This study aimed to assess the prognostic value and pro-oncogenic properties of HuR and its post-translational isoforms methyl-HuR and phospho-HuR in endometrial adenocarcinoma. Examining 89 endometrioid adenocarcinomas, we analyzed the relationship between HuR nuclear or cytoplasmic immunostaining, tumor-cell proliferation, and patient survival. HuR cytoplasmic expression was significantly increased in grade 3 vs. grade 1 adenocarcinomas (p < 0.001), correlating with worse overall survival (OS) (p = 0.02). Methyl-HuR cytoplasmic expression significantly decreased in grade 3 vs. grade 1 adenocarcinomas (p < 0.001) and correlated with better OS (p = 0.002). Phospho-HuR nuclear expression significantly decreased in grade 3 vs. grade 1 adenocarcinomas (p < 0.001) and non-significantly correlated with increased OS (p = 0.06). Cytoplasmic HuR expression strongly correlated with proliferation markers MCM6 (rho = 0.59 and p < 0.001) and Ki67 (rho = 0.49 and p < 0.001). Conversely, these latter inversely correlated with cytoplasmic methyl-HuR and nuclear phospho-HuR. Cytoplasmic HuR expression is a poor prognosis marker in endometrioid endometrial adenocarcinoma, while cytoplasmic methyl-HuR and nuclear phosphoHuR expressions are markers of better prognosis. This study highlights HuR as a promising potential therapeutic target, especially in treatment-resistant tumors, though further research is needed to understand the mechanisms regulating HuR subcellular localization and post-translational modifications.
Assuntos
Carcinoma Endometrioide , Proteína Semelhante a ELAV 1 , Neoplasias do Endométrio , Feminino , Humanos , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/metabolismo , Proliferação de Células , Citoplasma , Citosol , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Proteína Semelhante a ELAV 1/genética , Proteína Semelhante a ELAV 1/metabolismoRESUMO
Lymphovascular invasion (LVSI) is defined as the presence of tumor cells within a definite endothelial-lined space (lymphatics or blood vessels) in the organ surrounding invasive carcinoma. The presence of LVI is associated with an increased risk of lymph nodes and distant metastases. Lymphovascular invasion is described as cancer within blood or lymph vessels and is an independent risk factor for metastasis, recurrence, and mortality. This study aims to present the marker-based immunohistological characterization of cells around LVSI in a high-grade adenocarcinoma of the endometrium to build a cellular atlas of cells of LVSI. A cellular characterization of the cells around lymphovascular space invasion in a 67-year-old female patient with invasive high-grade serous endometrial adenocarcinomas is presented. Resected tumor tissue from a consented patient with invasive high-grade serous endometrial adenocarcinoma was obtained within an hour of surgery. The expressions of the epithelial markers (CK8, 18, and EpCAM), LCA (leukocyte common antigen) marker (CD45), proliferation marker (Ki67), apoptosis markers (cleaved PARP and cleaved caspase3), immune cell markers (CD3, CD4, CD8, CD56, CD68, CD163, FoxP3, PD-1, PD-L1), pro-inflammatory marker (IL-12-RB2), and fibroblast/mesenchyme markers (S100A7, SMA, and TE-7) of the resected tissue on the IHC stains were evaluated and scored by a pathologist. Acknowledging the deterministic role of LVSI in a high-grade adenocarcinoma of the endometrium, our study presents the first marker-based immunohistological atlas of the tumor and TME compartments in the context of epithelial cell markers, proliferation markers, apoptosis markers, macrophage markers, and fibroblast markers. Our study demonstrates that an aggressive disease like a high-grade adenocarcinoma of the endometrium inflicts the pro-metastatic event of LVSI by involving the immune landscape of both tumor and TME. This study demonstrates, for the first time, that the tumor cells within LVSI are positive for IL-12R-B2 and S100A4.
Assuntos
Adenocarcinoma , Neoplasias do Endométrio , Feminino , Humanos , Idoso , Neoplasias do Endométrio/patologia , Microambiente Tumoral , Invasividade Neoplásica/patologia , Endométrio/patologia , Adenocarcinoma/patologia , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
Adenomyosis is defined as the development of endometrial epithelial glands and stroma within the myometrial layer of the uterus. These "ectopic" lesions share many cellular characteristics with endometriotic epithelial cells as well as endometrial adenocarcinoma cells, including enhanced proliferation, migration, invasion and progesterone resistance. We recently reported that the 60S acidic ribosomal protein P1, RPLP1, is up-regulated in endometriotic epithelial cells and lesion tissue where it plays a role in cell survival. To evaluate if a similar pattern of expression and function for RPLP1 exists in adenomyosis and endometrial cancer, we examined RPLP1 expression in adenomyosis and endometrial cancer tissue specimens and assessed its function in vitro using well-characterized cell lines. A total of 12 control endometrial biopsies and 20 eutopic endometrial and matched adenomyosis biopsies as well as 103 endometrial adenocarcinoma biopsies were evaluated for RPLP1 localization by immunohistochemistry. Endometrial adenocarcinoma cell lines, Ishikawa, HEC1A, HEC1B and AN3 were evaluated for RPLP1 protein and transcript expression, while in vitro function was evaluated by knocking down RPLP1 expression and assessing cell survival and migration. RPLP1 protein was up-regulated in eutopic epithelia as well as in adenomyosis lesions compared to eutopic endometria from control subjects. RPLP1 was also significantly up-regulated in endometrial adenocarcinoma tissue. Knockdown of RPLP1 in endometrial adenocarcinoma cell lines was associated with reduced cell survival and migration. RPLP1 expression is up-regulated in eutopic and ectopic adenomyotic epithelia as well as in the epithelia of endometrial cancer specimens. In vitro studies support an essential role for RPLP1 in mediating cell survival and migration, processes which are all involved in pathophysiology associated with both diseases.
Assuntos
Adenocarcinoma , Adenomiose , Neoplasias do Endométrio , Endometriose , Neoplasias Uterinas , Feminino , Humanos , Adenocarcinoma/patologia , Adenomiose/patologia , Sobrevivência Celular/genética , Neoplasias do Endométrio/metabolismo , Endometriose/patologia , Endométrio/metabolismo , Células Epiteliais/metabolismo , Neoplasias Uterinas/patologiaRESUMO
AIM: To investigate the recurrence rate, live-birth rate, and treatment outcomes of levonorgestrel-releasing intrauterine device (LNG-IUD) for the management of atypical endometrial hyperplasia (AEH) or Grade-1 endometrial cancer (EC) in patients who desire fertility-sparing treatment and those seeking conservative treatment without fertility preservation. METHODS: We prospectively enrolled nine patients from a single institution between April 2009 and September 2013 who were followed up for 60 months after LNG-IUD insertion. RESULTS: The median patient age was 35 (range: 29-39) years. The overall recurrence rate was 56% (5/9). The median interval between removal of the LNG-IUD and recurrence was 20.5 (range: 2-30) months. Three of the nine patients had Grade-1 EC, and six had AEH. The response rates to the LNG-IUD in patients with Grade-1 EC and AEH were 66% and 100%, respectively. Four patients (three with AEH, one with Grade-1 EC) experienced recurrence 6 months after MPA treatment and all 4 (100%) had complete response. Eight patients desired fertility preservation, of which 37% (3/8) conceived after receiving fertility treatment and 25% (2/8) had a live birth; the remaining three had previously received MPA for 6 months and had a recurrence; of these, 1 had a live birth. CONCLUSION: LNG-IUD is effective for the management of AEH and EC in young patients who desire fertility-sparing treatment, including those ineligible for MPA owing to the presence of comorbidities and those with recurrence after MPA treatment (6-month treatment), and patients seeking conservative treatment without fertility preservation.
Assuntos
Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Dispositivos Intrauterinos Medicados , Feminino , Humanos , Adulto , Hiperplasia Endometrial/tratamento farmacológico , Levanogestrel/efeitos adversos , Dispositivos Intrauterinos Medicados/efeitos adversos , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/etiologiaRESUMO
AIM: This multicenter investigation was performed to evaluate the adjuvant treatment options, prognostic factors, and patterns of recurrence in patients with grade 3 endometrioid endometrial cancer (G3-EEC). MATERIALS AND METHODS: The medical reports of patients undergoing at least total hysterectomy and salpingo-oophorectomy for G3-EEC between 1996 and 2018 at 11 gynecological oncology centers were analyzed. Optimal surgery was defined as removal of all disease except for residual nodules with a maximum diameter ≤ 1 cm, as determined at completion of the primary operation. Adequate systematic lymphadenectomy was defined as the removal of at least 15 pelvic and at least 5 paraaortic LNs. RESULTS: The study population consists of 465 women with G3-EEC. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the entire cohort are 50.3% and 57.6%, respectively. Adequate systematic lymphadenectomy was achieved in 429 (92.2%) patients. Optimal surgery was achieved in 135 (75.0%) patients in advanced stage. Inadequate lymphadenectomy (DFS; HR 3.4, 95% CI 3.0-5.6; P = 0.016-OS; HR 3.2, 95% CI 1.6-6.5; P = 0.019) was independent prognostic factors for 5-year DFS and OS. CONCLUSION: Inadequate lymphadenectomy and LVSI were independent prognostic factors for worse DFS and OS in women with stage I-II G3-EEC. Adequate lymphadenectomy and optimal surgery were independent prognostic factors for better DFS and OS in women with stage III-IV G3-EEC.
Assuntos
Carcinoma Endometrioide , Neoplasias do Endométrio , Carcinoma Endometrioide/cirurgia , Intervalo Livre de Doença , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the impact of surgical lymph node assessment for clinically apparent, stage I endometrioid endometrial adenocarcinoma meeting Mayo criteria for lymphadenectomy. METHODS: Patients with endometrioid endometrial adenocarcinoma meeting Mayo criteria for lymphadenectomy who underwent hysterectomy and lymphadenectomy were identified. Algorithms for adjuvant therapy with and without lymphadenectomy were developed utilizing NCCN guidelines, PORTEC 1, and PORTEC 2. Patients served as their own control to determine the frequency of treatment modification. RESULTS: A total of 357 patients were analyzed. Using our algorithms treatment modification would have occurred because of lymphadenectomy in 62.8% of patients if whole pelvic external beam radiation was used for patients meeting inclusion criteria for PORTEC 1. Treatment modification would have occurred in 16.2% of patients if vaginal brachytherapy was used for patients meeting the inclusion criteria for PORTEC 2. Of the total, 53.8% of patients meeting inclusion criteria for PORTEC 1 would have had a reduction in adjuvant therapy from whole pelvic radiotherapy to vaginal brachytherapy alone. Only 9.0% of patients would have adjuvant therapy increased to include external beam radiotherapy and chemotherapy based on the presence of positive lymph nodes. CONCLUSIONS: Applying standard adjuvant treatment algorithms to real patient data, surgical lymph node assessment appears to frequently alter treatment allocation.
Assuntos
Algoritmos , Carcinoma Endometrioide/patologia , Tomada de Decisões , Neoplasias do Endométrio/patologia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Radioterapia Adjuvante/estatística & dados numéricos , Idoso , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirurgia , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Histerectomia/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
The 2021 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was the 20th anniversary of the symposia and held virtually on June 25th, in advance of the Society of Toxicologic Pathology's 40th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were presented to the audience for voting and discussion. Various lesions and topics covered during the symposium included differentiation of canine oligodendroglioma, astrocytoma, and undefined glioma with presentation of the National Cancer Institute's updated diagnostic terminology for canine glioma; differentiation of polycystic kidney, dilated tubules and cystic tubules with a discussion of human polycystic kidney disease; a review of various rodent nervous system background lesions in control animals from NTP studies with a focus on incidence rates and potential rat strain differences; vehicle/excipient-related renal lesions in cynomolgus monkeys with a discussion on the various cyclodextrins and their bioavailability, toxicity, and tumorigenicity; examples of rodent endometrial tumors including intestinal differentiation in an endometrial adenocarcinoma that has not previously been reported in rats; a review of various rodent adrenal cortex lesions including those that represented diagnostic challenges with multiple processes such as vacuolation, degeneration, necrosis, hyperplasia, and hypertrophy; and finally, a discussion of diagnostic criteria for uterine adenomyosis, atypical hyperplasia, and adenocarcinoma in the rat.
Assuntos
Adenocarcinoma , Neoplasias do Endométrio , Toxicologia , Animais , Cães , Feminino , Hiperplasia , Necrose , RatosRESUMO
INTRODUCTION: Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection. CASE REPORT: We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome.Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy. DISCUSSION: As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Rejeição de Enxerto/induzido quimicamente , Rejeição de Enxerto/cirurgia , Fatores Imunológicos/efeitos adversos , Transplante de Rim/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adenocarcinoma/complicações , Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Nefropatias/induzido quimicamente , Nefropatias/cirurgia , Pessoa de Meia-Idade , Nefrectomia , Resultado do TratamentoRESUMO
OBJECTIVES: Assess outcomes of a clinical cohort of patients with endometrioid endometrial cancer (EEC) harboring somatic POLE exonuclease domain mutations (EDMs). METHODS: Patients were consented to a protocol of tumor-normal massively parallel sequencing of 410-468 cancer related genes. EECs subjected to sequencing from 2014 to 2018 were reviewed. Tumors with somatic POLE EDMs were identified. EECs were assessed for microsatellite instability (MSI) using MSIsensor and immunohistochemical analysis for mismatch repair (MMR) proteins. RESULTS: Of the 451 EECs sequenced, 23 had a POLE EDM (5%): 20 primary and 3 recurrent tumors sequenced. Nineteen cases (83%) were stage I/II and 4 (17%) were stages III/IV. Thirteen EECs (57%) were of FIGO grades 1/2, 10 (43%) grade 3. All patients were treated with surgery and 17 (89%) received adjuvant therapy. Five (22%) demonstrated loss of DNA MMR protein expression, none were due to Lynch syndrome. MSIsensor scores were conclusive for 21 samples: 19 were microsatellite stable and 2 MSI-high. After median follow-up of 30 months, 4/23 (17%) developed recurrences: 3 with initial grade 3 stage I and 1 with grade 1 stage III disease. One patient with grade 2 stage IV EEC had progressive disease after treatment. CONCLUSIONS: Patients with POLE EDM EEC have been shown to have a favorable prognosis. In this real-world cohort of patients, de novo metastatic disease and recurrences in initially uterine-confined cases were observed. Further research is warranted before incorporating the presence of POLE EDM into decision-making regarding adjuvant therapy.
Assuntos
Carcinoma Endometrioide/genética , DNA Polimerase II/genética , Neoplasias do Endométrio/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Adulto , Idoso , Carcinoma Endometrioide/enzimologia , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Estudos de Coortes , Reparo de Erro de Pareamento de DNA , DNA Polimerase II/metabolismo , Neoplasias do Endométrio/enzimologia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: It is generally acknowledged that interobserver variability for the histological diagnosis of endocervical adenocarcinoma (EA) subtypes is suboptimal. The recently proposed International Endocervical Adenocarcinoma Criteria and Classification (IECC) system is based on the presence of associated human papilloma virus (HPV) infection. It recognises HPV-associated EAs and non-HPV-associated EAs. METHODS: This prospective cytology-histology and molecular genetics-based study investigated the potential effect of IECC being applied to Papanicolaou (Pap) test with regard to the diagnostic accuracy of severe glandular lesions reported at least as adenocarcinoma in situ (AIS). RESULTS: Out of 118 liquid-based cytology Pap tests with AIS+ lesion, complete information on follow-up biopsy and HPV status was available in 51 cases. AIS and EA category correlated with histologically confirmed AIS/EA in 88.5% (23/26) and 70.5% (12/17) of cases, respectively. Interestingly, 93% (40/43) of cases diagnosed as AIS/EA were HPV positive and 7% (3/43) were HPV negative (originating in the cervix, endometrium and adnexa). CONCLUSIONS: Our findings suggest that this approach could possibly divide Pap tests containing severe glandular lesion into two groups: (a) robust diagnosis of HPV-associated EA and (b) non-HPV associated glandular lesions of heterogeneous origin, requiring further clinical preoperative diagnostic workup.
Assuntos
Adenocarcinoma/diagnóstico , Detecção Precoce de Câncer , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Adenocarcinoma/classificação , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Citodiagnóstico/métodos , Feminino , Humanos , Teste de Papanicolaou/métodos , Infecções por Papillomavirus/classificação , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Esfregaço Vaginal/métodos , Displasia do Colo do Útero/classificação , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
We aimed at finding the impact of prior malignancies on the survival of patients with endometrial adenocarcinoma using SEER database (from 1973 to 2014). We identified 127,988 patients who were diagnosed with endometrial adenocarcinoma (6485 had a prior malignancy), and we compared the overall and cancer-specific survival based on the presence or absence of a prior malignancy and the latency period between the two diagnoses using Kaplan-Meier test and Cox models. Adjusted cox models showed that a history of a prior malignancy neither affected the overall survival nor the cancer-specific survival of stage IV cases in all latency groups except the one diagnosed within 1 year of the first cancer. Therefore, there is no rational explanation for excluding stage IV endometrial adenocarcinoma patients with a prior malignancy from clinical trials except for the group that was diagnosed with endometrial adenocarcinoma within 1 year from the first cancer.Impact statementWhat is already known on this subject? Not enough evidence is found on the impact of prior malignancies on the survival of patients with subsequent endometrial adenocarcinoma.What do the results of this study add? History of a prior malignancy neither affects the overall survival of stage IV endometrial adenocarcinoma nor the cancer-specific survival. Only patients who had their second malignancy diagnosed within one year of the first malignancy should be excluded from clinical trials, while patients diagnosed within one to five years of the first cancer should be encouraged to enrol in clinical trials as they have an enhanced survival than patients without a history of malignancy.What are the implications of these findings for clinical practice and/or further research? We recommend that future researchers should consider including the aforementioned group of patients in their trials to achieve more accurate results and in order not to strip the patients of potential therapeutic benefits of enrolling in clinical trials.
Assuntos
Adenocarcinoma/mortalidade , Neoplasias do Endométrio/mortalidade , Segunda Neoplasia Primária/mortalidade , Seleção de Pacientes , Adenocarcinoma/patologia , Adulto , Idoso , Ensaios Clínicos como Assunto , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Modelos de Riscos Proporcionais , Programa de SEERRESUMO
We report a case of Eggerthella lenta bacteraemia. An elderly lady with metastasised endometrial adenocarcinoma presented with complaints of fever nausea vomiting and abdominal pain. CT scan of the abdomen showed enlarged liver with multiple metastatic lesions raising suspicion of small-bowel obstruction. Due to multiple comorbid conditions, surgery was contraindicated and she was treated empirically with meropenem and vancomycin. Blood culture received on admission grew Eggerthela lenta.
Assuntos
Adenocarcinoma , Bacteriemia , Infecções por Bactérias Gram-Positivas , Actinobacteria , Adenocarcinoma/complicações , Idoso , Bacteriemia/complicações , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Feminino , Humanos , PaquistãoRESUMO
Differentiation of endocervical adenocarcinomas involving the uterine corpus from primary endometrial (EM) carcinomas involving the cervix is, not only clinically but also pathologically, often difficult. We report a case of gastric-type endocervical adenocarcinoma involving the corpus that could be correctly diagnosed because it was a unique endocervical adenocarcinoma subtype. A 69-year-old woman who presented with abnormal genital bleeding was diagnosed as having a uterine adenocarcinoma on pathological examination of EM biopsy. Preoperative imaging findings and a surgical specimen showed that the tumor was mainly located in the corpus and involved the cervix. We considered at first that the tumor was an EM adenocarcinoma invading into the cervix. However, results of an immunohistochemical examination indicated that it was a gastric-type mucinous adenocarcinoma derived from the endocervix. Our final pathological diagnosis was a gastric-type endocervical adenocarcinoma spreading to the uterine corpus.
Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Carcinoma/diagnóstico , Neoplasias do Endométrio/diagnóstico , Neoplasias Gástricas/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma Mucinoso/patologia , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Gástricas/patologia , Neoplasias do Colo do Útero/patologia , Útero/patologiaRESUMO
Ovarian teratomas are occasionally reported in dogs; the rarest type is the monophasic teratoma, composed of tissues originating from only one germ layer. Canine endometrial adenocarcinomas are also rare in dogs and mainly affect geriatric females. This report describes the case of co-existing ovarian teratoma and uterine adenocarcinoma in a 10-year-old nulliparous female Boxer presented with lethargy, anorexia and purulent vaginal discharge. Abdominal ultrasonography evidenced pyometra and a mass in the left ovary. This was composed of a uniform whitish tissue with multiple cystic structures. The histology revealed an atrophy of the ovarian parenchyma, compressed by a proliferation of well-differentiated nervous tissue staining positively to vimentin, S100 and neuronal specific enolase (NSE), and negatively to keratin and inhibin. The left uterine horn, whose diameter was markedly increased, showed foci of endometrial cellular atypia, evident nucleoli and mitoses, at light microscopy. To our best knowledge, this is the first report of a co-existing ovarian monophasic teratoma and endometrial adenocarcinoma, two rare reproductive neoplasia in dogs.
Assuntos
Adenocarcinoma/veterinária , Doenças do Cão/patologia , Neoplasias Ovarianas/veterinária , Teratoma/veterinária , Neoplasias Uterinas/veterinária , Adenocarcinoma/patologia , Animais , Doenças do Cão/diagnóstico por imagem , Cães , Feminino , Neoplasias Ovarianas/patologia , Teratoma/patologia , Ultrassonografia/veterinária , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: The effects of quercetin and selenium on oxidative stress in endometrial adenocarcinoma cells are unclear. In this study, the effects of quercetin and selenium on oxidative stress caused by both hydrogen peroxide and UV radiation in endometrial adenocarcinoma cells were examined. METHODS: The viability of endometrial adenocarcinoma cells cultured in vitro and treated with different concentrations of quercetin and sodium selenite was measured using the MTT assay. Malondialdehyde (MDA) levels were investigated, and expression levels of BAD and p53 genes were analysed using realtime quantitative polymerase chain reaction. Acridine orange/ethidium bromide staining technique was applied to detect apoptosis. Mass attenuation coefficient of each quercetin and sodium selenite combinations was evaluated using Monte Carlo simulation. RESULTS: The combination of quercetin and sodium selenite enhanced cell viability, and reduced MDA levels. The expression levels of BAD and p53 genes decreased by combined treatment with quercetin and selenium while showing synergistic effects in terms of gene expression. Fluorescent microscopic examination showed a decrease in apoptotic cells in endometrial adenocarcinoma cells treated with the combination of quercetin and selenium. CONCLUSIONS: For the first time, selenium and quercetin have synergistic cytoprotective and radioprotective effects on oxidative stress caused by hydrogen peroxide in endometrial adenocarcinoma cells for the first time (Tab. 1, Fig. 7, Ref. 39).
Assuntos
Adenocarcinoma , Neoplasias do Endométrio , Estresse Oxidativo , Quercetina , Selênio , Adenocarcinoma/patologia , Apoptose , Neoplasias do Endométrio/patologia , Feminino , Humanos , Peróxido de Hidrogênio , Malondialdeído , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Selênio/farmacologiaRESUMO
BACKGROUND: The large-conductance, voltage-gated, calcium (Ca (2+))-activated potassium channel (BKCa) plays an important role in regulating Ca (2+) signaling and cell physiological function, and is aberrantly expressed in some types of cancers. The present study focuses on identifying the oncogenic potential and clinical significance of BKCa in endometrial adenocarcinoma, as well as exploring the mechanistic relevance by 17ß -estradiol (E2) inducing aberrant activation of MEK1/2 and ERK1/2 via BKCa. METHODS: The expression of BKCa, ERK1/2 and p-ERK1/2 were examined by immunohistochemical staining in 263 cases, including 185 primary types I endometrial cancer tissues, 38 atypical endometrial hyperplasia tissues and 40 normal endometrium tissues. Cell growth, cycle, apoptosis rate, migration and invasion was separately tested in Ishikawa cells using siRNA-BKCa and/or E2 treatment, as well as the expression of these interested proteins by western blot analysis. RESULTS: We showed that expression of BKCa is significantly elevated in 185 types I endometrial adenocarcinoma tissues compared to those of the normal endometrium and atypical endometrial hyperplasia tissues. Furthermore, in vitro observations revealed that down-regulation of BKCa expression inhibited cell growth by both enhancing apoptosis and blocking G1/S transition, suppressed cell migration and invasion in Ishakiwa cells, and decreased the expression of p-MEK1/2 and p-ERK1/2. Additionally, RNAi-mediated knockdown of BKCa attenuated the increased cellular growth and invasion, as well as the elevated expression of p-MEK1/2 and p-ERK1/2 proteins, induced by E2 stimulation. More importantly, the aberrant expression of BKCa and p-ERK1/2 were closely related with poor prognostic factors in type I endometrial cancer, and up-regulated expression of p-ERK1/2 was significantly associated with shorter disease-free survival (DFS) and overall survival (OS) and was an independent prognostic factor in type I endometrial cancer patients. CONCLUSION: Our results demonstrated that BKCa and the key downstream effectors p-ERK1/2 could be involved in important signaling pathways in initiation and development of endometrial adenocarcinoma and may provide a new therapeutic approach for women with endometrial cancer.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias do Endométrio/metabolismo , Estradiol/metabolismo , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Transdução de Sinais/fisiologia , Adenocarcinoma/patologia , Apoptose/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Regulação para Baixo/fisiologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Regulação para Cima/fisiologiaRESUMO
Endometrial cancer is one of the most common female pelvic cancers and has been considered an androgen-related malignancy. Several studies have demonstrated the anti-cell proliferative effect of androgen on endometrial cancer cells; however, the mechanisms of the anti-cancer effect of androgen remain largely unclear. 17ß-hydroxysteroid dehydrogenase type 2 (17ß-HSD2), which catalyzes the conversion of E2 to E1, is known to be upregulated by androgen treatment in breast cancer cells. In this study, we therefore focused on the role of androgen on estrogen dependence in endometrial cancer. Dihydrotestosterone (DHT) was found to induce 17ß-HSD2 mRNA and protein expression in HEC-1B endometrial cancer cells. DHT could also inhibit cell proliferation of HEC-1B when induced by estradiol treatment. In 19 endometrioid endometrial adenocarcinoma (EEA) tissues, intratumoral DHT concentration was measured by liquid chromatography/electrospray tandem mass spectrometry and was found to be significantly correlated with 17ß-HSD2 immunohistochemical status. We further examined the correlations between 17ß-HSD2 immunoreactivity and clinicopathological parameters in 53 EEA tissues. 17ß-HSD2 status was inversely associated with the histological grade, clinical stage, and cell proliferation marker Ki-67, and positively correlated with progesterone receptor expression. 17ß-HSD2 status tended to be positively associated with androgen receptor status. In 53 EEA cases, the 17ß-HSD2-positive group tended to have better prognosis than that for the negative group with respect to progression-free survival and endometrial cancer-specific survival. These findings suggest that androgen suppresses the estrogen dependence of endometrial cancer through the induction of 17ß-HSD2 in endometrial cancer.
Assuntos
Androgênios/farmacologia , Carcinoma Endometrioide/metabolismo , Di-Hidrotestosterona/farmacologia , Neoplasias do Endométrio/metabolismo , Estradiol Desidrogenases/metabolismo , Transdução de Sinais , Idoso , Androgênios/metabolismo , Carcinoma Endometrioide/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Di-Hidrotestosterona/metabolismo , Neoplasias do Endométrio/patologia , Estradiol Desidrogenases/genética , Feminino , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Although acotiamide hydrochloride hydrate (acotiamide-HH) has not been reported to have genotoxic findings in any of the genotoxicity studies or treatment-related toxicological findings in reproductive and developmental studies, suspicious uterine tumorigenesis was observed in the results of a long-term rat carcinogenicity study. To clarify the uterine tumorigenesis of acotiamide-HH, we performed a 2-stage uterine carcinogenicity model in the transgenic rasH2 mouse initiated by N-Ethyl-N-nitrosourea (ENU). This model facilitated the short-term detection of uterine carcinogenic potential, and it appears to be a very useful testing method for assessing the safety of chemicals that may affect uterine tumorigenesis. However, there have not been many reports on this model, and accumulation of case studies using this model is recommended to support its usability. In this study, we performed this carcinogenesis model to not only confirm uterine tumorigenesis of acotiamide-HH but also to confirm the reliability of the model. The results of this study revealed that the endometrial adenocarcinoma found in the long-term rat carcinogenicity study possibly arose spontaneously. Also, we confirmed early induction of a uterine tumor as in previous reports and confirmed that 26 weeks is the appropriate treatment period for this rasH2 mouse model according to time-course observations of uterine tumor development.
RESUMO
Stroma-tumor communication participates in the pathogenesis of endometrial carcinomas. In previous studies, we found that normal stromal cells inhibited the growth of endometrial carcinoma cells. Here, we investigated the role of normal stromal cells in the epithelial-mesenchymal transition (EMT) of endometrial carcinoma cells and explored the possible mechanism implied. We found that conditioned medium (CM) by normal endometrial stromal cells (NSC) reduced cell growth and induced cell apoptosis in Ishikawa cells. CM by NSC inhibited 17ß-estradiol-induced cell growth and apoptosis decrease in Ishikawa cells. Moreover, CM by NSC inhibited the migration and invasion, and 17ß-estradiol-induced migration and invasion in Ishikawa cells. Meanwhile, CM by NSC decreased Slug expression and 17ß-estradiol-induced Slug expression, increased E-cadherin expression and abolished 17ß-estradiol-induced E-cadherin reduction in Ishikawa cells. In conclusion, normal stromal factors can inhibit 17ß-estradiol-induced cell proliferation and apoptosis inhibition, and abolished 17ß-estradiol-induced EMT in endometrial cancer cell via regulating E-cadherin and Slug expression.
Assuntos
Adenocarcinoma/metabolismo , Caderinas/metabolismo , Neoplasias do Endométrio/metabolismo , Endométrio/metabolismo , Transição Epitelial-Mesenquimal , Estradiol/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Adulto , Antígenos CD , Linhagem Celular Tumoral , Feminino , Humanos , Células Estromais/metabolismoRESUMO
BACKGROUND: Exfoliated endometrial cells can be seen in cervical smears in association with a wide variety of conditions ranging from normal proliferative endometrium to endometrial malignancies. It is often difficult to differentiate between benign, atypical and malignant endometrial cells using cytomorphology alone. This study was conducted to evaluate if morphometric analysis of endometrial nuclei on liquid-based cervical samples could be of help in differentiating between these endometrial cells. MATERIALS AND METHODS: Three groups of cervical samples with histopathological correlation were selected: Group A: showing benign endometrial cells; Group B: showing atypical endometrial cells and Group C: showing malignant endometrial cells. There were 30 cases each in Group A and B and 39 cases in Group C. Image J, NIH, USA was used for selecting the endometrial nuclei and performing the morphometric measurements. MANOVA was used for statistical analysis. RESULTS: The mean nuclear area and nuclear perimeter were significantly different between the three groups of endometrial cells with a P-value <0.05. However, the mean standard deviation of the nuclear area (SDNA) was not significantly different between atypical and malignant endometrial cells (P = 0.765) and the mean nuclear diameter was not statistically different between benign and atypical cells (P = 0.112). Also, the difference in the mean integrated gray density amongst all three groups was not statistically significant (P = 0.397, 0.844, 0.732). CONCLUSION: We conclude that the morphometric parameters of the nuclear area and nuclear perimeter are helpful in differentiating between benign, atypical and malignant endometrial nuclei even in liquid-based cervical cytology samples.