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1.
BMC Cancer ; 21(1): 946, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425774

RESUMO

BACKGROUND: In patients with average risk of bleeding, second-look endoscopy does not reportedly reduce bleeding after gastric endoscopic submucosal dissection. However, effectiveness of second-look endoscopy for patients with a high risk of bleeding, such as those who are taking antithrombotic agents, is unclear. Hence, this study aims to clarify the effectiveness of second-look endoscopy for patients with antithrombotic therapy. METHODS: We studied 142 consecutive patients with 173 gastric epithelial neoplasms who were routinely taking antithrombotic agents and were treated by endoscopic submucosal dissection at Tonan Hospital between November 2013 and December 2019. They were classified into two groups: those with second-look endoscopy (SLE group, 69 patients with 85 lesions) and those without second-look endoscopy (non-SLE group, 73 patients with 88 lesions). The incidence of post-endoscopic submucosal dissection bleeding was compared between the SLE and non-SLE groups. RESULTS: There were no statistical differences in the rate of patients undergoing single antiplatelet therapy, single anticoagulant therapy, and multiple therapy between the SLE and non-SLE groups (SLE group vs. non-SLE group; 32 [46.4%], 16 [23.2%], and 21 [30.4%] patients vs. 37 [50.7%], 20 [27.4%], and 16 [21.9%] patients, respectively; p = 0.50). Post-endoscopic submucosal dissection bleeding incidence was 21.7% (15/69) and 21.9% (16/73) in the SLE and non-SLE groups, respectively, and did not significantly differ between the two groups (p = 0.98). CONCLUSIONS: For patients taking antithrombotic agents, the incidence of post-endoscopic submucosal dissection bleeding was not reduced by second-look endoscopy.


Assuntos
Ressecção Endoscópica de Mucosa/efeitos adversos , Fibrinolíticos/efeitos adversos , Gastroscopia/efeitos adversos , Neoplasias Epiteliais e Glandulares/terapia , Hemorragia Pós-Operatória/prevenção & controle , Cirurgia de Second-Look/métodos , Neoplasias Gástricas/terapia , Idoso , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Epiteliais e Glandulares/patologia , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/etiologia , Prognóstico , Neoplasias Gástricas/patologia
2.
Int J Mol Sci ; 22(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207601

RESUMO

The current statistics on cancer show that 90% of all human cancers originate from epithelial cells. Breast and prostate cancer are examples of common tumors of epithelial origin that would benefit from improved drug treatment strategies. About 90% of preclinically approved drugs fail in clinical trials, partially due to the use of too simplified in vitro models and a lack of mimicking the tumor microenvironment in drug efficacy testing. This review focuses on the origin and mechanism of epithelial cancers, followed by experimental models designed to recapitulate the epithelial cancer structure and microenvironment, such as 2D and 3D cell culture models and animal models. A specific focus is put on novel technologies for cell culture of spheroids, organoids, and 3D-printed tissue-like models utilizing biomaterials of natural or synthetic origins. Further emphasis is laid on high-content imaging technologies that are used in the field to visualize in vitro models and their morphology. The associated technological advancements and challenges are also discussed. Finally, the review gives an insight into the potential of exploiting nanotechnological approaches in epithelial cancer research both as tools in tumor modeling and how they can be utilized for the development of nanotherapeutics.


Assuntos
Bioimpressão , Neoplasias da Mama , Modelos Biológicos , Neoplasias Epiteliais e Glandulares , Organoides , Impressão Tridimensional , Neoplasias da Próstata , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Masculino , Nanotecnologia , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Organoides/diagnóstico por imagem , Organoides/metabolismo , Organoides/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Engenharia Tecidual
3.
Sci Rep ; 11(1): 13864, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226620

RESUMO

MicroRNAs (miRs) are small non-coding RNA molecules, which are involved in the development of various malignancies, including prostate cancer (PCa). miR-17-5p is considered the most prominent member of the miR-17-92 cluster, with an essential regulatory function of fundamental cellular processes. In many malignancies, up-regulation of miR-17-5p is associated with worse outcome. In PCa, miR-17-5p has been reported to increase cell proliferation and the risk of metastasis. In this study, prostatectomy specimens from 535 patients were collected. Tissue microarrays were constructed and in situ hybridization was performed, followed by scoring of miR-17-5p expression on different tumor compartments. High expression of miR-17-5p in tumor epithelium was associated with biochemical failure (BF, p < 0.001) and clinical failure (CF, p = 0.019). In multivariate analyses, high miR-17-5p expression in tumor epithelial cells was an independent negative prognostic factor for BF (HR 1.87, 95% CI 1.32-2.67, p < 0.001). In vitro analyses confirmed association between overexpression of miR-17-5p and proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145). In conclusion, our study suggests that a high cancer cell expression of miR-17-5p was an independent negative prognostic factor in PCa.


Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Epitélio/metabolismo , Epitélio/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/patologia , Prognóstico , Neoplasias da Próstata/patologia
4.
Clin Radiol ; 76(8): 585-592, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34059294

RESUMO

AIM: To investigate the value of contrast-enhanced dual-energy spectral computed tomography (CT) in differentiating borderline epithelial ovarian tumours (BEOTs) from malignant epithelial ovarian tumours (MEOTs). MATERIALS AND METHODS: Sixty patients who underwent pelvic contrast-enhanced spectral CT were divided into two groups for analysis based on the tumour types confirmed at histopathological examination (26 BEOTs and 34 MEOTs). The regions of interest (ROIs) were selected on solid tumour components to measure attenuation values on monochromatic image sets (40-140 keV) in all imaging phases and tumour iodine concentrations (IC) on material decomposition images. Differences in the attenuation value between the unenhanced and contrast-enhanced phases (enhancement degree) and between energy strengths (slope k, k = [attenuation at 40 keV- attenuation at 140 keV]/100) were calculated. All measurements between the two groups were compared with independent t-test. Receiver operating characteristic (ROC) curves were generated to calculate the sensitivity, specificity and area under the ROC curve (AUC). Logistic regression analysis was used to evaluate the diagnostic efficacy of using combined parameters in two-phase contrast-enhanced images. RESULTS: In the arterial phase (AP) and venous phase (VP), the BEOTs had significantly lower enhancement than MEOTs from 40 to 100 keV (p<0.05). The k values and IC values both showed significant differences in the AP and VP (p<0.05). Combining parameters in two contrast-enhanced phases provided 80.8% sensitivity and 82.4% specificity in differentiating MEOTs from BEOTs with an AUC of 0.844. CONCLUSION: Dual-energy spectral CT provides a multiparametric approach in differentiating BEOTs from MEOTs with the best diagnostic efficacy using combined parameters in the AP and VP images.


Assuntos
Meios de Contraste , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Ovário/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
5.
Int J Mol Sci ; 22(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946233

RESUMO

Neoplasms derived from follicular tissue are extremely rare. Clinically, they are reported as non-symptomatic, slow-growing nodules. These lesions are mainly benign, but the malignant type can occur. Mainly middle-aged people (50-60 years of age) are affected. These carcinomas are mainly localized on the head and neck or torso. They can be locally aggressive and infiltrate surrounding tissue and metastasize to regional lymph nodes. In the minority of cases, distant metastases are diagnosed. Quick and relevant diagnosis is the basis of a treatment for all types of tumors. The patient's life expectancy depends on multiple prognostic factors, including the primary tumor size and its mitotic count. Patients should be referred to a specialized skin cancer center to receive optimal multidisciplinary treatment. This article tries to summarize all the information that is currently available about pathogenesis, diagnosis, and treatment methods of follicular tumors.


Assuntos
Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Cutâneas/diagnóstico , Animais , Carcinogênese/patologia , Gerenciamento Clínico , Humanos , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/terapia , Pele/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
6.
Mol Med Rep ; 24(1)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33955501

RESUMO

The aim of the present study was to investigate the effects of human epididymis protein 4 (HE4) on drug resistance and its underlying mechanisms. The associations among proteins were detected by immunoprecipitation and immunofluorescence assays. Then, stably transfected cell lines CAOV3­HE4­L and CAOV3­A2­L expressing HE4 short hairpin (sh)RNAs and ANXA2 shRNAs, respectively, were constructed. MTT assay, immunocytochemistry, western blotting, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and flow cytometry were employed to examine drug sensitivity, as well as the expression and activity of P­glycoprotein (P­gp). HE4 and P­gp in epithelial ovarian cancer tissues were assessed via immunohistochemistry. MicroRNAs that targeted the P­gp gene, ABCB1, were predicted using bioinformatics methods, and their expression was evaluated by RT­qPCR. The common signaling pathways shared by HE4, ANXA2 and P­gp were selected by Gene Set Enrichment Analysis (GSEA). The interaction of HE4, ANXA2 and P­gp were confirmed. P­gp expression was positively associated with HE4 and ANXA2 expression, respectively. Moreover, it was observed that there was no significant rescue of P­gp expression in CAOV3­A2­L cells following the administration of active HE4 protein. In addition, the expression of HE4 and P­gp in ovarian cancer tissues of drug­resistant patients were higher compared with that of the drug­sensitive group (P<0.05). Furthermore, the results revealed that hsa­miR­129­5p was significantly increased accompanied by decreased HE4 or ANXA2 expression and P­gp expression in CAOV3­HE4­L and CAOV3­A2­L cells. GSEA analyses disclosed that HE4, ANXA2 and P­gp genes were commonly enriched in the signaling pathway involved in regulating the actin cytoskeleton. These results indicated that HE4 promotes P­gp­mediated drug resistance in ovarian cancer cells through the interactions with ANXA2, and the underlying mechanism may be associated with decreased expression of hsa­miR­129­5p and dysregulation of the actin cytoskeleton signaling pathway.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Anexina A2/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Citoesqueleto de Actina/genética , Citoesqueleto de Actina/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Transdução de Sinais/genética , Análise de Sobrevida , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/genética
7.
Biochim Biophys Acta Rev Cancer ; 1876(1): 188538, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33862149

RESUMO

Twenty mucin genes have been identified and classified in two groups (encoding secreted and membrane-bound proteins). Secreted mucins participate in mucus formation by assembling a 3-dimensional network via oligomerization, whereas membrane-bound mucins are anchored to the outer membrane mediating extracellular interactions and cell signaling. Both groups have been associated with carcinogenesis progression in epithelial cancers, and are therefore considered as potential therapeutic targets. In the present review, we discuss the link between mucin expression patterns and patient survival and propose mucins as prognosis biomarkers of epithelial cancers (esophagus, gastric, pancreatic, colorectal, lung, breast or ovarian cancers). We also investigate the relationship between mucin expression and overall survival in the TCGA dataset. In particular, epigenetic mechanisms regulating mucin gene expression, such as aberrant DNA methylation and histone modification, are interesting as they are also associated with diagnosis or prognosis significance. Indeed, mucin hypomethylation has been shown to be associated with carcinogenesis progression and was linked to prognosis in colon cancer or pancreatic cancer patients. Finally we describe the relationship between mucin expression and non-coding RNAs that also may serve as biomarkers. Altogether the concomitant knowledge of specific mucin-pattern expression and epigenetic regulation could be translated as biomarkers with a better specificity/sensitivity performance in several epithelial cancers.


Assuntos
Biomarcadores Tumorais/genética , Epigênese Genética , Mucinas/genética , Neoplasias Epiteliais e Glandulares/genética , Animais , Biomarcadores Tumorais/metabolismo , Montagem e Desmontagem da Cromatina , Metilação de DNA , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Mucinas/metabolismo , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Prognóstico , RNA não Traduzido/genética , RNA não Traduzido/metabolismo
8.
Med Sci Monit ; 27: e929152, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33737504

RESUMO

BACKGROUND Lacrimal gland pleomorphic adenoma (LGPA) is the most common clinically benign epithelial tumor of the lacrimal gland and is predominantly comprised of epithelial cells and interstitial components. At present, the exact pathogenesis of LGPA remains unclear. Previous research has indicated that the occurrence of LGPA may be related to excessive cell proliferation. MATERIAL AND METHODS This study observed the clinicopathological characteristics of LGPA and investigated the tumorigenesis mechanism of cell over-proliferation caused by the imbalance between apoptosis and proliferation. A total of 27 cases were collected from the Department of Ophthalmology of the Affiliated Hospital of Chengde Medical University and the Third Medical Center of Chinese PLA General Hospital from April 2017 to November 2019. Hematoxylin-eosin (HE) staining and immunohistochemical staining were used to observe the pathological characteristics and analyze the expression of bcl-2 and bax in the lacrimal gland. RESULTS Compared with normal lacrimal gland tissues, LGPA tumor tissues had obvious changes in pathological morphology. The expression of bcl-2 in LGPA lesion tissues was dramatically higher (P<0.001), the expression of bax was not significantly different between groups (P=0.25), but the ratio of bcl-2/bax was significantly higher in tumor tissues (P=0.01). CONCLUSIONS We found that the lacrimal gland tumor tissues had obvious excessive proliferation in pathomorphology, which revealed the necessity of complete surgical removal of the capsule from the perspective of pathological morphology and provided a theoretical basis for the hypothesis that the imbalance between apoptosis and proliferation could lead to cell hyperproliferation.


Assuntos
Adenoma Pleomorfo/metabolismo , Adenoma Pleomorfo/patologia , Aparelho Lacrimal/patologia , Adulto , Apoptose/fisiologia , Carcinogênese/metabolismo , Proliferação de Células/fisiologia , Transformação Celular Neoplásica/patologia , Neoplasias Oculares/patologia , Neoplasias Oculares/cirurgia , Feminino , Humanos , Doenças do Aparelho Lacrimal/patologia , Doenças do Aparelho Lacrimal/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Proteína X Associada a bcl-2/análise
9.
Diagn Pathol ; 16(1): 22, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712056

RESUMO

BACKGROUND: Sialadenoma papilliferum (SP) is an extremely rare benign neoplasm of salivary glands. To explore and define the clinicopathological features of SP, we retrospectively analyzed 89 cases previously reported and five new cases. METHODS: The clinical features, histopathology, immunohistochemistry and molecular analysis of our cases were further performed and the related literatures were reviewed and analyzed. RESULTS: Combining 89 cases from the literature with our cases, the hard palate was the most common locations for SP. However, two of our cases were rarely located in the esophageal mucosa. Among all cases, the male gender was more affected, with the average age and median age of 61.8 and 62 years, respectively. Conventional histomorphologically, SP was characterized by complex papillary structures with a biphasic growth pattern of exophytic squamous component and endophytic glandular component. The glandular structures were lined by a double layer of epithelium composed of flattened or cuboidal basal cells and a cuboidal or columnar luminal cells formed papillary infoldings into the ductal lumina. Immunohistochemically, the luminal epithelial configurations showed strong expression of CK7 along the luminal cell membrane, while the basal myoepithelia displayed strong nuclear p63 expression. In both the glandular and squamous tumour components showed BRAF V600E-positive immunostaining and BRAF V600E mutation. CONCLUSION: For the first time, we have comprehensively aggregated and analyzed 90 cases sialadenoma papilliferum from almost all previous publications, and further explored the clinicopathological features of SP; concordantly, this study demonstrated that SP shows a papillomatous growth pattern with exophytic and endophytic proliferation of ductal epithelium composed of double-layered cells harboring BRAF V600E mutation. Additionly, adequate treatment for SP is surgical excision, with a favorable prognosis in patients.


Assuntos
Epitélio/patologia , Neoplasias Epiteliais e Glandulares/patologia , Papiloma/patologia , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia , Adulto , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/diagnóstico
10.
Radiol Clin North Am ; 59(2): 169-182, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33551079

RESUMO

Thymic epithelial neoplasms, as classified by the World Health Organization, include thymoma, thymic carcinoma, and thymic carcinoid. They are a rare group of tumors and are often diagnosed incidentally in the work-up of parathymic syndrome, such as myasthenia gravis, or when mass effect or local invasion causes other symptoms. In each of these scenarios, understanding the radiologic-pathologic relationship of these tumors allows clinical imagers to contribute meaningfully to management decisions and overall patient care. Integrating important imaging features, such as local invasion, and pathologic features, such as necrosis and immunohistochemistry, ensures a meaningful contribution by clinical imagers to the care team.


Assuntos
Diagnóstico por Imagem/métodos , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologia , Humanos , Timo/diagnóstico por imagem , Timo/patologia
11.
Radiol Clin North Am ; 59(2): 183-192, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33551080

RESUMO

Thymic epithelial neoplasms are a group of malignant tumors that includes thymoma, thymic carcinoma, and thymic neuroendocrine tumors. Although several staging systems have been developed over the years for use with these cancers, they have been interpreted and implemented in a nonuniform manner. Recently, the International Association for the study of Lung Cancer and the International Thymic Malignancy Interest Group developed a tumor-node-metastasis staging system that has been universally accepted and correlates with patient survival and outcomes. Although pathologic staging is determined by histologic examination of the resected tumor, imaging plays an important role in clinical staging and is important for informing therapeutic decisions.


Assuntos
Diagnóstico por Imagem/métodos , Metástase Linfática/diagnóstico por imagem , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologia , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Estadiamento de Neoplasias , Timo/diagnóstico por imagem , Timo/patologia
12.
Nat Med ; 27(3): 419-425, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33558725

RESUMO

Genetically engineered T cell therapy can induce remarkable tumor responses in hematologic malignancies. However, it is not known if this type of therapy can be applied effectively to epithelial cancers, which account for 80-90% of human malignancies. We have conducted a first-in-human, phase 1 clinical trial of T cells engineered with a T cell receptor targeting HPV-16 E7 for the treatment of metastatic human papilloma virus-associated epithelial cancers (NCT02858310). The primary endpoint was maximum tolerated dose. Cell dose was not limited by toxicity with a maximum dose of 1 × 1011 engineered T cells administered. Tumor responses following treatment were evaluated using RECIST (Response Evaluation Criteria in Solid Tumors) guidelines. Robust tumor regression was observed with objective clinical responses in 6 of 12 patients, including 4 of 8 patients with anti-PD-1 refractory disease. Responses included extensive regression of bulky tumors and complete regression of most tumors in some patients. Genomic studies, which included intra-patient tumors with dichotomous treatment responses, revealed resistance mechanisms from defects in critical components of the antigen presentation and interferon response pathways. These findings demonstrate that engineered T cells can mediate regression of common carcinomas, and they reveal immune editing as a constraint on the curative potential of cellular therapy and possibly other immunotherapies in advanced epithelial cancer.


Assuntos
Neoplasias Epiteliais e Glandulares/patologia , Papillomaviridae/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/metabolismo , Linhagem Celular Tumoral , Humanos , Metástase Neoplásica , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/virologia
14.
Am J Surg Pathol ; 45(7): 885-894, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33481388

RESUMO

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland cancer characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells. Because of its histologic variety and overlap of histologic features with other salivary gland tumors, there are broad differential diagnoses. The HRAS Q61R mutation has been reported to be frequent in and specific to EMC. We evaluated the usefulness of RAS Q61R mutant-specific immunohistochemical (IHC) staining for detecting this genetic alteration in EMC. We investigated 83 EMC cases and 66 cases of salivary gland tumors with an EMC-like component, including pleomorphic adenoma, adenoid cystic carcinoma, basal cell adenoma/adenocarcinoma, and myoepithelial carcinoma. Sanger sequencing was performed for HRAS, KRAS, and NRAS. The diffuse and membranous/cytoplasmic RAS Q61R IHC expression was observed in 65% of EMC cases, in which all cases harbored the HRAS Q61R mutation. IHC-positive cases were present only in de novo EMCs (54/76 cases, 71%) but not in EMCs ex pleomorphic adenoma. The immunoreactivity was almost always restricted to the myoepithelial cells. Conversely, all EMC cases lacking the HRAS Q61R mutation were negative on IHC. In addition, only 3% of EMC-like tumors showed the abovementioned immunopositivity. None of the cases examined carried KRAS or NRAS mutations. IHC for RAS Q61R is highly sensitive and specific for detecting the HRAS Q61R mutation in EMC. Since significant immunopositivity was almost exclusively identified in nearly two thirds of EMCs but seldom in the histologic mimics, the IHC of RAS Q61R is a useful tool for diagnosing EMC in general pathology laboratories.


Assuntos
Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Imuno-Histoquímica , Mutação , Mioepitelioma/genética , Neoplasias Epiteliais e Glandulares/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias das Glândulas Salivares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mioepitelioma/patologia , Neoplasias Epiteliais e Glandulares/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia
15.
Hum Pathol ; 110: 62-72, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32920035

RESUMO

Thyroid cancer therapy is increasingly tailored to patients' risk of recurrence and death, placing renewed importance on pathologic parameters. The International Collaboration on Cancer Reporting (ICCR), an organization promoting evidence-based, internationally agreed-upon standardized pathology data sets, is the ideal conduit for the development of a pathology reporting protocol aimed at improving the care of patients with thyroid carcinomas. An international expert panel reviewed each element of thyroid pathology reporting. Recommendations were made based on the most recent literature and expert opinion.The data set uses the most recent World Health Organization (WHO) classification for the purpose of a more clinically and prognostically relevant nomenclature. One example is the restriction of the term minimally invasive follicular carcinoma to tumors with capsular invasion only. It reinforces the already established criteria for blood vessel invasion adopted by the most recent WHO classification and Armed Forces Institute of Pathology fascicle. It emphasizes the importance of the extent of blood vessel invasion and extrathyroid extension to better stratify patients for appropriate therapy. It is the first data set that requires pathologists to use the more recently recognized prognostically powerful parameters of mitotic activity and tumor necrosis. It highlights the importance of assessing nodal disease volume in predicting the risk of recurrence.The ICCR thyroid data set provides the tools to generate a report that will guide patient treatment in a more rational manner aiming to prevent the undertreatment of threatening malignancies and spare patients with indolent tumors the morbidity of unnecessary therapy. We recommend its routine use internationally for reporting thyroid carcinoma histology.


Assuntos
Carcinoma/patologia , Neoplasias Epiteliais e Glandulares/patologia , Patologia Clínica/normas , Projetos de Pesquisa/normas , Neoplasias da Glândula Tireoide/patologia , Humanos , Recidiva Local de Neoplasia/patologia
16.
Ann Thorac Surg ; 112(1): 271-277, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33068543

RESUMO

BACKGROUND: In stage III to IVa thymic epithelial tumors (TETs), infiltration of the superior vena cava (SVC) is not rare. The extent of SVC resection depends on the width of the area of neoplastic invasion. Our article aims to evaluate the safety and long-term outcomes of extended thymectomy for TETs with SVC resection compared with advanced-stage TETs patients without SVC resection. METHODS: Retrospective review of the experience on patients who underwent extended thymectomy for TETs in the last 20 years, according to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) methodology. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A backward stepwise Cox regression multivariate analysis was performed to determine factors associated with long-term outcomes. RESULTS: A total of 78 patients underwent surgery for advanced-stage TETs (Masaoka-Koga stages III-IVa) from January 1998 to April 2019. Fourteen (17.9%) underwent thymectomy with resection of SVC. Presence of a thymic carcinoma (hazard ratio , 2.26; 95% confidence interval, 1.82-6.18; P = .038) and the SVC resection (hazard ratio, 1.89; 95% confidence interval, 1.11-3.96; P = .041) were adverse prognostic factors at multivariate analysis. The median OS and the PFS of all SVC resected patients were 50 (range, 5-207) months and 31 (range, 5-151) months, respectively. There was no significant difference in OS (P = .28) and PFS (P = .32) between SVC-resected and non-SVC-resected patients. CONCLUSIONS: SVC resection is a safe and effective procedure to restore the venous system continuity and does not seem to affect survival and disease recurrence. This surgical approach allows radical resection of locally advanced TETs, even after neoadjuvant chemotherapy.


Assuntos
Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias do Timo/cirurgia , Veia Cava Superior/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Neoplasias Epiteliais e Glandulares/patologia , Pneumonectomia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Timectomia/métodos , Neoplasias do Timo/patologia , Veia Cava Superior/patologia
17.
Int J Cancer ; 148(7): 1586-1597, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33022785

RESUMO

Cancer of unknown primary (CUP) is a metastasised malignancy with no identifiable primary tumour origin. Despite the frequent occurrence and bleak prognosis of CUP, research into its aetiology is scarce. Our study investigates alcohol consumption, tobacco smoking and CUP risk. We used data from the Netherlands Cohort Study, a cohort that includes 120 852 participants aged 55 to 69 years, who completed a self-administered questionnaire on cancer risk factors at baseline. Cancer follow-up was established through record linkage to the Netherlands Cancer Registry and Dutch Pathology Registry. After 20.3 years of follow-up, 963 CUP cases and 4288 subcohort members were available for case-cohort analyses. Multivariable-adjusted hazard ratios (HRs) were calculated using proportional hazard models. In general, CUP risk increased with higher levels of alcohol intake (Ptrend = .02). The association was more pronounced in participants who drank ≥30 g of ethanol per day (HR: 1.57, 95% confidence interval [CI]: 1.20-2.05) compared to abstainers. Current smokers were at an increased CUP risk (HR: 1.59, 95% CI: 1.29-1.97) compared to never smokers. We observed that the more the cigarettes or the longer a participant smoked, the higher the CUP risk was (Ptrend = .003 and Ptrend = .02, respectively). Interaction on additive scale was found for participants with the highest exposure categories of alcohol consumption and cigarette smoking frequency and CUP risk. Our findings demonstrate that alcohol consumption and cigarette smoking are associated with increased CUP risk. Lifestyle recommendations for cancer prevention regarding not drinking alcohol and avoiding exposure to smoking are therefore also valid for CUP.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Fumar Cigarros/efeitos adversos , Neoplasias Epiteliais e Glandulares/etiologia , Neoplasias Primárias Desconhecidas/etiologia , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/mortalidade , Neoplasias Primárias Desconhecidas/patologia , Países Baixos/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Inquéritos e Questionários
18.
Thorac Cardiovasc Surg ; 69(2): 148-156, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32898892

RESUMO

BACKGROUND: Although tumor size is included in the definition of T descriptor in the tumor-node-metastasis (TNM) classification of many solid tumors, it is not considered for thymomas. This study aimed to assess the relationship of tumor diameters (the largest tumor diameter [LTD] and the mean tumor diameter [MTD]) with survival in thymoma patients undergoing surgical resection in a single center. METHODS: The study included 127 thymoma patients (age, 49.2 ± 15.2 years; 65 males), who were evaluated based on pathological tumor sizes according to the LTD and MTD ([largest diameter + shortest diameter] / 2) and divided into three subgroups for each parameter as: patients with an LTD of ≤5 cm, 5.1 to 10 cm, and >10 cm and patients with an MTD of ≤5, 5.1 to 10, and >10 cm. RESULTS: In thymoma patients, survival significantly differed according to the presence of myasthenia gravis (p = 0.018), resection status (R0 or R1; p = 0.001), T status (p = 0.015), and the Masaoka-Koga stage (p = 0.003). In the LTD subgroups, the overall survival of those with R0 resection was lower in those with an LTD of 5.1 to 10 cm than in those with an LTD of ≤5 cm (p = 0.051) and significantly lower in those with an MTD of 5.1 to 10 cm than in those with an MTD of ≤5 cm (p = 0.027). In the MTD subgroups, survival decreased as the tumor size increased. CONCLUSION: Both smaller tumor size and complete resection are associated with better survival in thymoma patients. Therefore, the largest or the mean tumor size might be considered as a criterion in the TNM staging for thymoma.


Assuntos
Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Timectomia , Timoma/patologia , Timoma/cirurgia , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia , Carga Tumoral , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/mortalidade , Radioterapia Adjuvante , Fatores de Risco , Timectomia/efeitos adversos , Timectomia/mortalidade , Timoma/mortalidade , Neoplasias do Timo/mortalidade , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Cancer Res ; 81(2): 438-451, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33229340

RESUMO

Tumors are complex tissues composed of transformed epithelial cells as well as cancer-activated fibroblasts (CAF) that facilitate epithelial tumor cell invasion. We show here that CAFs and other mesenchymal cells rely much more on glutamine than epithelial tumor cells; consequently, they are more sensitive to inhibition of glutaminase. Glutamine dependence drove CAF migration toward this amino acid when cultured in low glutamine conditions. CAFs also invaded a Matrigel matrix following a glutamine concentration gradient and enhanced the invasion of tumor cells when both cells were cocultured. Accordingly, glutamine directed invasion of xenografted tumors in immunocompromised mice. Stimulation of glutamine-driven epithelial tumor invasion by fibroblasts required previous CAF activation, which involved the TGFß/Snail1 signaling axis. CAFs moving toward Gln presented a polarized Akt2 distribution that was modulated by the Gln-dependent activity of TRAF6 and p62 in the migrating front, and depletion of these proteins prevented Akt2 polarization and Gln-driven CAF invasion. Our results demonstrate that glutamine deprivation promotes CAF migration and invasion, which in turn facilitates the movement of tumor epithelial cells toward nutrient-rich territories. These results provide a novel molecular mechanism for how metabolic stress enhances invasion and metastasis. SIGNIFICANCE: Cancer-associated fibroblasts migrate and invade toward free glutamine and facilitate invasion of tumor epithelial cells, accounting for their movement away from the hostile conditions of the tumor towards nutrient-rich adjacent tissues. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/2/438/F1.large.jpg.


Assuntos
Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/patologia , Movimento Celular , Transição Epitelial-Mesenquimal , Glutamina/farmacologia , Neoplasias Epiteliais e Glandulares/patologia , Animais , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Int J Gynecol Pathol ; 40(2): 175-179, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32168063

RESUMO

High-grade serous carcinoma has a variety of different growth patterns, but is typically easily recognizable to pathologists and rarely confused with serous borderline tumors. We report a case of a 71-yr-old woman with a unilateral 5.1 cm ovarian cyst with small papillary projections on contrast-enhanced magnetic resonance imaging of the pelvis. Histologic examination showed a noninvasive papillary neoplasm with hierarchical branching and epithelial proliferation, and thus, at low magnification, bearing a striking resemblance to a serous borderline tumor. However, a more careful examination demonstrated high-grade cytologic features, nuclear pleomorphism, and abundant mitotic activity, suggestive of high-grade serous carcinoma. The morphology and immunohistochemical profile of this lesion is consistent with a rare, purely noninvasive growth pattern of high-grade serous carcinoma. This lesion represents the "far left" of the high-grade ovarian serous carcinoma morphologic spectrum and can mimic a serous borderline tumor.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico por imagem , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Cistos Ovarianos/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Idoso , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Histerectomia , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Cistos Ovarianos/patologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia
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