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1.
Medicine (Baltimore) ; 99(39): e22322, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991441

RESUMO

RATIONALE: Bronchiolar adenoma (BA) is a newly designated rare entity of the lung, including both the currently designated ciliated muconodular papillary tumor (CMPT) and so-called non-classic CMPT. The most prominent histological feature of BAs is the bilayered cell structures composed of the continuous basal cell layer and the luminal layer which consists of different proportion of mucinous cells, ciliated cells, Clara cells and/or type II pneumocytes. BA purely covered by mucinous cells without other components in the luminal layer has never been reported. PATIENT CONCERNS: An 82-year-old female patient was detected a 0.8 cm ground glass nodule in the left lower lobe of the lung. DIAGNOSES: The serum levels of tumor markers were normal. INTERVENTIONS: The patient underwent a segmentectomy of the left lower lobe. OUTCOMES: The postoperative pathological diagnosis was BA. Molecular analysis revealed that the tumor harbored ALK rearrangement and BRAF mutations simultaneously. There was no recurrence in 17 months of follow-up. LESSONS: BA can be lined only by mucinous cells, without any cuboidal and/or ciliated cells in the surface layer. This sets a dangerous pitfall in differentiation diagnosis with invasive mucinous adenocarcinoma especially during intraoperative frozen pathological diagnosis.


Assuntos
Adenoma/metabolismo , Bronquíolos/patologia , Neoplasias Pulmonares/patologia , Biologia Molecular/métodos , Adenoma/cirurgia , Assistência ao Convalescente , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/metabolismo , Biomarcadores Tumorais/sangue , Feminino , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Pneumonectomia/métodos , Proteínas Proto-Oncogênicas B-raf/metabolismo , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(34): e21841, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846831

RESUMO

RATIONALE: Ovarian microcystic stromal tumor is a relatively rare tumor type, which is characterized by morphology with microcyst structure, solid cellular areas, and hyalinized fibrous stroma. The most reported tumors were stage I with good prognosis. PATIENT CONCERNS: We report a case of a 33-year-old woman with primary ovarian microcystic stromal tumor with significant bizarre nuclei. We describe the clinical, histopathological, and immunohistochemical findings and review the English literatures. So far, as we know, the patient presented here is a rare case of ovarian microcystic stromal tumor with prominent bizarre nuclei accounting for about 50% of the tumor cells. DIAGNOSES: She was diagnosed with ovarian microcystic stromal tumor with significant bizarre nuclei. INTERVENTIONS: The right ovarian tumor was resected laparoscopically on October 19, 2018. OUTCOMES: Up to now, the patient is free of disease at 19 months of follow-up. LESSONS: This is a rare case of ovarian microcystic stromal tumor with obvious bizarre nuclei. This report will contribute to expand the morphological spectrum of ovarian microcystic stromal tumor.


Assuntos
Núcleo Celular/patologia , Neoplasias Ovarianas/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia , beta Catenina/metabolismo , Adulto , Assistência ao Convalescente , Biomarcadores Tumorais/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica/métodos , Laparoscopia/métodos , Resultado do Tratamento
3.
Methods Mol Biol ; 2203: 119-134, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833209

RESUMO

Well-differentiated primary airway epithelial cell (AEC) cultures have been widely used for the characterization of several human respiratory viruses including coronaviruses. In recent years, there has been an increase in interest toward animal AEC cultures and their application to characterize veterinary viruses with zoonotic potential, as well as studying host-pathogen interactions in animal reservoir host species. In this chapter, we provide a revised and improved protocol for the isolation and establishment of well-differentiated AEC cultures from diverse mammalian species and the use of the cultures for the characterization of veterinary coronavirus. We also describe immunohistochemistry protocols with validated antibodies for the visualization and identification of viral cell tropism in well-differentiated AEC cultures from human, swine, bovine, and feline origin.


Assuntos
Brônquios/citologia , Coronavirus/fisiologia , Células Epiteliais/virologia , Cultura Primária de Células/métodos , Traqueia/citologia , Animais , Gatos , Bovinos , Diferenciação Celular , Células Epiteliais/citologia , Imunofluorescência , Humanos , Imuno-Histoquímica/métodos , Cultura Primária de Células/instrumentação , Suínos , Tropismo Viral
4.
Orv Hetil ; 161(35): 1436-1440, 2020 08.
Artigo em Húngaro | MEDLINE | ID: mdl-32822321

RESUMO

Neuropeptides synthetised in the enteric nervous system can change the function of the immunocells and play a role in inflammatory processes. In our review the effects of inflammation on the neuropeptide content of nerves and immune cells were compared. Inflamed tissue samples (human gastritis and animal models with experimental colitis and streptozotocin-induced diabetes mellitus) were examined. The number and contacts of neuropeptide-containing nerves and immune cells were studied using immunohistochemistry, confocal laser microscopy and electronmicroscopy. In inflammation, the number of substance P, vasoactive intestinal polypeptide and neuropeptide Y nerve fibres was increased significantly in parallel with the strongly increased number of immunocompetent cells (p<0.001). In inflammatory diseases, a large number of lymphocytes and mast cells were also positive for these neuropeptides. Very close morphological relationship between substance P and neuropeptide Y immunoreactive nerve fibres and immunocells could be demonstrated only in inflamed mucosa. Some of the substance P immunoreactive immunocells were also immunoreactive for tumor necrosis factor alpha and nuclear factor kappa B in the case of inflammation. The increased number of tumor necrosis factor alpha and nuclear factor kappa B immunoreactive immune cells correlated with the increased number of substance P-containing nerve fibres. Substance P, vasoactive intestinal polypeptide and neuropeptide Y released from nerve fibres and immunocells can play a role in inflammation. Our results suggest that using substance P antagonists or vasoactive intestinal polypeptide and neuropeptide Y peptides might be a novel therapeutic concept in the management of inflammation. Orv Hetil. 2020; 161(35): 1436-1440.


Assuntos
Inflamação/terapia , Neuropeptídeo Y/metabolismo , Substância P/metabolismo , Substância P/uso terapêutico , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Imuno-Histoquímica/métodos , Inflamação/imunologia , Inflamação/metabolismo , Fibras Nervosas/imunologia , Fibras Nervosas/metabolismo , Neuropeptídeo Y/imunologia , Neuropeptídeo Y/uso terapêutico , Substância P/imunologia , Peptídeo Intestinal Vasoativo/imunologia , Peptídeo Intestinal Vasoativo/uso terapêutico
5.
J Cancer Res Clin Oncol ; 146(11): 2861-2870, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32772171

RESUMO

PURPOSE: IGF-1Ec is an isoform of Insulin-like growth factor 1 (IGF-1) and has recently been identified to be overexpressed in cancers including prostate and neuroendocrine tumours. The aim of this paper is to investigate the expression of IGF-1Ec in colorectal cancer and polyps compared to normal colon tissues and its association with recurrent disease using semi-quantitative immunohistochemistry. METHODS: Immunohistochemistry for IGF-1Ec expression was performed for colorectal cancer, colorectal polyps and normal colonic tissues. The quantification of IGF-1Ec expression was performed with the use of Image J software and the IHC profiler plugin. Following ethics approval from the National Research Ethics Service (Reference 11/LO/1521), clinical information including recurrent disease on follow-up was collected for patients with colorectal cancer. RESULTS: Immunohistochemistry was performed in 16 patients with colorectal cancer and 11 patients with colonic polyps and compared to normal colon tissues and prostate adenocarcinoma (positive control) tissues. Significantly increased expression of IGF-1Ec was demonstrated in colorectal cancer (p < 0.001) and colorectal polyps (p < 0.05) compared to normal colonic tissues. Colonic adenomas with high-grade dysplasia had significantly higher expression of IGF-1Ec compared to low-grade dysplastic adenomas (p < 0.001). Colorectal cancers without lymph node metastases at the time of presentation had significantly higher IGF-1Ec expression compared to lymph node-positive disease (p < 0.05). No correlation with recurrent disease was identified with IGF-1Ec expression. CONCLUSION: IGF-1Ec is significantly overexpressed in colorectal cancer and polyps compared to normal colon tissues offering a potential target to improve colonoscopic identification of colorectal polyps and cancer and intraoperative identification of colorectal tumours.


Assuntos
Pólipos Adenomatosos/diagnóstico , Pólipos do Colo/diagnóstico , Neoplasias Colorretais/diagnóstico , Fator de Crescimento Insulin-Like I/metabolismo , Pólipos Adenomatosos/metabolismo , Pólipos Adenomatosos/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Pólipos do Colo/metabolismo , Pólipos do Colo/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Fator de Crescimento Insulin-Like I/análise , Masculino
6.
PLoS One ; 15(8): e0238120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833992

RESUMO

PURPOSE: Conjunctival squamous cell carcinoma (SCC) is primarily treated with surgical resection. SCC has various stages, and local recurrence is common. The purpose of this study was to determine molecular localization of epidermal growth factor receptor (EGFR) and the possibility of EGFR as a biomarker for the management of conjunctival SCC. METHODS: In this retrospective study, we performed immunohistochemistry to evaluate EGFR expression and localization in tumor cells, EGFR mutation-specific expression (E746-A750del and L858R), and human papillomavirus expression in a series of 29 conjunctival SCCs. RESULTS: All 29 tumors in our cohort were EGFR positive (100%). Twenty-one of 29 tumors (72%) showed focal EGFR staining, and seven (28%) showed diffuse EGFR staining. In addition, we calculated the percentages of the two most important mutations in EGFR (exon 19 746-A750del (8/29, 27.5%), exon 21 (L858R mutant (2/29, 6.8%)) in conjunctival SCCs. We observed that the translocation of EGFR from the membrane into the cytoplasm was related to clinical prognosis, as we detected correlations between EGFR cytoplasmic staining and final orbital exenteration and between decreased EGFR membrane staining and progression-free survival. CONCLUSIONS: EGFR is important in the pathology of ocular surface squamous neoplasia including SCC and is a prognostic factor. Increased understanding of EGFR mutations may have important implications for future treatment options.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias da Túnica Conjuntiva/genética , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Estudos de Coortes , Neoplasias da Túnica Conjuntiva/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/genética , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos
7.
Ann Diagn Pathol ; 48: 151600, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32805515

RESUMO

The vaccine BCG has been reported to offer protection against SARS-CoV-2 infection. It has been hypothesized this is based on nonspecific enhancement of innate immunity. This study addressed whether there is strong homology between a SARS-CoV-2 capsid protein and a Mycobacterium bovis protein that would allow for stronger, more specific immune protection. The study also showed the utility of immunohistochemistry in the diagnostic pathology laboratory for elucidating this information. Immunohistochemistry documented that an antibody directed against the SARS-CoV-2 envelope, but not the spike or membrane proteins, strongly cross hybridized to 11/11 Mycobacterial species tested, including M. bovis. BlastP analysis showed high homology of the SARS-CoV-2 envelope protein with 12 consecutive amino acids of the protein LytR C, which is a consensus protein unique to Mycobacteria. Six additional cases of human tuberculosis with few organisms showed that the viral envelope specific antibody (5/6) was more accurate than the AFB stain (2/6) for diagnostic purposes. These data indicate BCG vaccination induces a specific immunity against SARS CoV-2 that targets the viral envelope protein that is essential for infectivity. Thus, a concurrent booster or first use of the BCG vaccine may reduce the severity of the current COVID-19 pandemic. The data also suggests the value of using the SARS-CoV-2 envelope antibody in the diagnosis of Mycobacterial infections in formalin fixed, paraffin embedded tissues by the diagnostic pathologist.


Assuntos
Antígenos Virais/imunologia , Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Mycobacterium/imunologia , Pneumonia Viral/imunologia , Tuberculose/imunologia , Anticorpos Antivirais/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Reações Cruzadas , Humanos , Imuno-Histoquímica/métodos , Pandemias , Tuberculose/diagnóstico , Proteínas do Envelope Viral/imunologia
8.
Arch Virol ; 165(10): 2373-2377, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32761270
9.
Medicine (Baltimore) ; 99(27): e21119, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629746

RESUMO

INTRODUCTION: Myeloid sarcoma (MS) is a rare tumor mass. It may occur at any extramedullary anatomic sites but is uncommon in the sinonasal location.MS commonly presents concurrently with acute myeloid leukemia (AML), but it may predate AML over several months or years, named isolated MS. PATIENT CONCERNS: We report a case of a 15-month-old child who presented with mouth breathing, bilateral rhinorrhea, palpebral edema and proptosis. The routine blood tests were normal for the first few months. Computed tomography scan revealed neoplasm in nasal cavity. DIAGNOSIS: The patient was definitely diagnosed with isolated MS in the nasal cavity through immunohistochemistry combined with clinical features and radiological investigations, and MS further progressed to AML which was confirmed by hematologist. INTERVENTIONS: Endoscopic sinus surgery was performed to acquire specimens. After diagnosis, the patient was promptly treated with systemic chemotherapy. OUTCOMES: All symptoms gradually subsided and the mass of nasal cavity was invisible. No relapse occurred during follow-up. CONCLUSION: Sinonasal MS may be misdiagnosed and should be considered when symptoms persist and worsen. Prompt clinic examinations are essential for cases with suspected MS. Diagnosis of MS is dependent on the immunohistological investigations combined with clinical features, radiological investigations. Early diagnosis and systemic chemotherapy are vital for patients to achieve best prognosis.


Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Cavidade Nasal/diagnóstico por imagem , Sarcoma Mieloide/complicações , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Erros de Diagnóstico/prevenção & controle , Diagnóstico Precoce , Edema/etiologia , Exoftalmia/etiologia , Doenças Palpebrais/patologia , Humanos , Imuno-Histoquímica/métodos , Lactente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/cirurgia , Masculino , Cavidade Nasal/patologia , Cavidade Nasal/cirurgia , Sarcoma Mieloide/diagnóstico por imagem , Sarcoma Mieloide/metabolismo , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
10.
J Histotechnol ; 43(3): 153-158, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32643596

RESUMO

COVID-19 disease in humans, caused by the novel SARS-CoV-2 virus, was first reported in the city of Wuhan, China in December 2019. This disease has quickly developed into a global pandemic, resulting in over 350,000 deaths worldwide and over 5 million confirmed infections in a matter of 6 months. Although the genome of this novel viral RNA was sequenced quickly and testing kits were manufactured to assist in combatting COVID-19, the diagnosis and treatment will remain relatively unsuccessful until the pathology of this disease is fully understood. Histotechnology plays an important role in understanding the pathology of many diseases, including COVID-19. The first postmortem biopsy of a COVID-19 patient was collected on 27 January 2020, and the pathology finding was published in mid-February 2020. Since then, more studies have been published in scientific literatures as the global outbreak continues. This mini-review summarizes the published articles in which histotechnology aspects were utilized with the intent to understand the pathology of COVID-19. In addition, it is anticipated there will be more molecular and immunohistochemical studies to further understand the mechanism of the disease in the near future.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/patologia , Surtos de Doenças/prevenção & controle , Pneumonia Viral/patologia , Infecções por Coronavirus/virologia , Humanos , Imuno-Histoquímica/métodos , Pandemias , Pneumonia Viral/virologia , RNA Viral/genética
11.
Ann Diagn Pathol ; 48: 151565, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32659620

RESUMO

Infection by SARS-CoV-2 commonly begins in the nasopharynx, and the cytologic and molecular correlates are not characterized. Fifty-eight cytologic preps (20 oral and 38 from the nasopharynx) were obtained from ten patients and analyzed in a blinded fashion for SARS-CoV-2 spike and envelope protein by immunohistochemistry and viral RNA by in situ hybridization. qRTPCR identified three positive cases and seven controls; the three cases reported mild symptoms that resolved in 2-3 days. Blinded analyses confirmed the presence of the SARS-CoV-2 spike and envelope proteins and viral RNA in the three cases and viral absence in the seven controls. A signal for the positive cases was evident in each nasopharyngeal and none of the oral samples. Viral RNA/proteins localized exclusively to glandular cells and was present in high copy number. Blinded analysis of the cytology documented that the glandular cells infected by SARS-CoV-2 showed marked degeneration with ciliocytophthoria; viral inclusions were not evident. Co-expression analysis showed viral infected cells had increased apoptosis, marked by strong expression of activated caspase 3. Weekly serial testing of two of the cases showed persistence of productive viral infection for up to 2 weeks after symptom onset. It is concluded that the target cell of SARS-CoV-2 in the head and neck region is the glandular cell of the nasal passages, that viral infection is lytic and associated with high copy number that facilitates viral spread. The method outlines a simple, rapid test for productive SARS-CoV-2 based on immunohistochemistry or in situ hybridization of the glandular cells from the nasopharynx.


Assuntos
Infecções por Coronavirus/diagnóstico , Citodiagnóstico/métodos , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Nasofaringe/virologia , Pneumonia Viral/diagnóstico , Betacoronavirus , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/virologia , RNA Viral/análise , Proteínas Virais/análise
12.
Lab Invest ; 100(11): 1485-1489, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32647285

RESUMO

Coronavirus Disease-19 (COVID-19), caused by the coronavirus SARS-CoV-2, was initially recognized in Wuhan, China and subsequently spread to all continents. The disease primarily affects the lower respiratory system, but may involve other organs and systems. Histopathologic evaluation of tissue from affected patients is crucial for diagnostic purposes, but also for advancing our understanding of the disease. For that reason, we developed immunohistochemical (IHC) and in situ hybridization (ISH) assays for detection of the. virus. A total of eight autopsy lungs, one placenta, and ten kidney biopsies from COVID-19 patients were stained with a panel of commercially available antibodies for IHC and commercially available RNA probes for ISH. Similarly, autopsy lungs, placentas and renal biopsies from non-COVID-19 patients were stained with the same antibodies and probes. All eight lungs and the placenta from COVID-19 patients stained positive by IHC and ISH, while the kidney biopsies stained negative by both methodologies. As expected, all specimens from non-COVID-19 patients were IHC and ISH negative. These two assays represent a sensitive and specific method for detecting the virus in tissue samples. We provide the protocols and the list of commercially available antibodies and probes for these assays, so they can be readily implemented in pathology laboratories and medical examiner offices for diagnostic and research purposes.


Assuntos
Betacoronavirus/isolamento & purificação , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Feminino , Humanos , Indicadores e Reagentes , Rim/virologia , Pulmão/virologia , Inclusão em Parafina , Placenta/virologia , Gravidez
13.
Medicine (Baltimore) ; 99(28): e20825, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664075

RESUMO

INTRODUCTION: Primary bladder mucosa-associated lymphoid tissue (MALT) lymphoma is a rare tumor. To date, the PubMed database contains only 39 English articles covering 63 cases of primary bladder MALT lymphoma. Herein, we report a case of this disease and review the current literature. PATIENT CONCERNS: A 77-year-old woman presented with frequent urination, urinary urgency, and dysuria for 3 years. In the past 3 years, the patient's symptoms recurred and progressively worsened, and she was admitted to the hospital. DIAGNOSIS: A histopathological examination revealed the bladder mass as a tumor with high proliferation of atypical B-lymphocytes. Immunohistochemistry showed positive results for CD20, PAX-5, Ki-67, BCL-2, and CD21 and negative results for CD10, MUM1, TDT, and cyclin D1. These data supported the diagnosis of primary bladder MALT lymphoma. INTERVENTIONS: A transurethral resection of bladder tumor was performed to treat the disease. OUTCOMES: The patient was alive and healthy at the 15-month follow-up. CONCLUSION: Primary bladder MALT lymphoma is a rare disease and can be easily missed or misdiagnosed before achieving a histological confirmation. Surgery may be the best choice for both diagnosis and treatment.


Assuntos
Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias da Bexiga Urinária/patologia , Transtornos Urinários/etiologia , Adolescente , Adulto , Assistência ao Convalescente , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Cistoscopia/métodos , Feminino , Humanos , Imuno-Histoquímica/métodos , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgia , Transtornos Urinários/fisiopatologia , Adulto Jovem
14.
J Cancer Res Clin Oncol ; 146(9): 2299-2310, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32556504

RESUMO

BACKGROUND: Although much progress has been made in the diagnosis of early-stage lung adenocarcinoma (ES-LUAD), the prognosis for ES-LUAD patients with rapid recurrence is still poor. Importantly, there is currently no effective and precise method to screen patients who may develop rapid recurrence. Therefore, it is necessary to identify potential differentially expressed genes (DEGs) in ES-LUAD patients with rapid recurrence and non-rapid recurrence. METHODS: Affymetrix GeneChip Human Transcriptome Array was used to identify DEGs between ES-LUAD patients with rapid recurrence and non-rapid recurrence. Rapid recurrence was defined as recurrence-free survival (RFS) â‰¦ 1 year and non-rapid recurrence was defined as RFS â‰§ 3 years. The biological functions of the DEGs were analyzed by GO and KEGG pathway enrichment analyses. The protein-protein interaction (PPI) network of identified DEGs was conducted by STRING and Cytoscape software. The expression level of crucial hub genes and tumor-infiltrating lymphocytes (TILs) was verified by immunohistochemistry (IHC). RESULTS: A total of 416 DEGs were identified between ES-LUAD patients with and without rapid recurrence. The results of GO analysis revealed that 2 of the top 10 categories in the domain of cellular component, 2 of the top 10 in the domain of molecular function, and 9 of the top 10 in the domain of biological process were functionally related to immunity. The results of KEGG analysis showed that 6 of the top 8 pathways were functionally involved in immune regulation and inflammatory response. The PPI network analysis identified ten crucial nodal protein, including EGFR, MMP9, IL-1ß, PTGS2, MMP1, and 5 histone proteins, which constituted 25 key interactions. IL-1ß and PTGS2 expression were closely related to immunity and IHC analysis further revealed that low expression of IL-1ß and PTGS2 is associated with rapid recurrence. Kaplan-Meier analysis further revealed that LUAD patients with lower IL-1ß or PTGS2 expression had a worse RFS. When the TIL density of CD3+, CD4+, CD8+ and CD20+ subsets was less than 20%, ES-LUAD patients have a higher probability of rapid recurrence. CONCLUSION: There were significant differences in the expression of immune-related genes between patients with rapid recurrence and patient with non-rapid recurrence. Immune-related genes such as IL-1ß and PTGS2 and TIL density (20%) play important roles in rapid recurrence of ES-LUAD. This study provided a theoretical basis for distinguishing the two types of patients from an immunological perspective.


Assuntos
Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Redes Reguladoras de Genes/genética , Humanos , Imuno-Histoquímica/métodos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Mapas de Interação de Proteínas/genética , Transcriptoma/genética
15.
Medicine (Baltimore) ; 99(26): e20854, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590784

RESUMO

INTRODUCTION: Although primary hepatic neuroendocrine carcinomas, whose prognostic mechanisms remain unclear, are rare, coexistence of neuroendocrine carcinomas and other tumors is rarer. In this report, we describe a unique case of coexistence between primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma in the pancreas. PATIENT CONCERNS: A 64-year-old woman with a history of diabetes, but none of hepatitis, was admitted to hospital because of intermittent epigastric distension and pain discomfort for more than 1 month aggravated 1 day. A contrast-enhanced computed tomography (CT) scan of the upper abdomen and abdominal magnetic resonance imaging (MRI) revealed a thickening of the bile duct wall in the middle and lower segment of common bile duct and the corresponding lumen is narrow and low-density tumors with ring enhancement (1.83 cm × 1.9 cm) in lobi hepatis dexte. DIAGNOSIS: Primary neuroendocrine carcinoma of the liver was diagnosed to be coexisting with a distal cholangiocarcinoma, which had invaded the pancreas. Immunohistochemical examination revealed that the neoplastic cells strongly expressed chromogranin A, synaptophysin, and CD56 proteins. The tumor cells did not express HepPar-1, glypican-3, S-100, CK7, and CK19 in the liver tumor. A distal bile duct in pancreatic tissues shows the characteristics of typical bile duct carcinoma, as an invasion of carcinoma is also seen in the pancreatic tissues. Gastrointestinal endoscopy, chest and abdominal CT, abdominal MRI, and positron emission tomography (PET)-CT were used to exclude metastatic neuroendocrine tumors of the liver. INTERVENTIONS: Resection of the pancreas-duodenum, the right anterior lobe of the liver, and regional lymph nodes was performed in patients. OUTCOMES: The patient had survived for 5 months after the operation. CONCLUSION: A unique case of a coexistence of primary hepatic neuroendocrine carcinoma and a distal cholangiocarcinoma, which had invaded the pancreas. No treatment guidelines are established for the treatment of the unique case.


Assuntos
Carcinoma Neuroendócrino/diagnóstico , Colangiocarcinoma/diagnóstico , Fígado/anormalidades , Antígeno CD56/análise , Antígeno CD56/sangue , Carcinoma Neuroendócrino/patologia , Colangiocarcinoma/patologia , Cromogranina A/análise , Cromogranina A/sangue , Feminino , Humanos , Imuno-Histoquímica/métodos , Fígado/patologia , Fígado/fisiopatologia , Pessoa de Meia-Idade , Prognóstico , Sinaptofisina/análise , Sinaptofisina/sangue , Tomografia Computadorizada por Raios X/métodos
16.
J Clin Pathol ; 73(10): 656-664, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32591352

RESUMO

AIMS: Programmed death-1/programmed death ligand 1 (PD-1/PD-L1) inhibitor therapy is accompanied by companion or complementary PD-L1 testing in some tumour types. We investigated utilisation of the Dako PD-L1 IHC 28-8 and 22C3 pharmDx assays and the Ventana PD-L1 (SP142) assay and evaluated concordance between the 28-8 and 22C3 assays in a real-world cohort of patients tested at a single US national reference laboratory. METHODS: NeoGenomics Laboratories performed PD-L1 testing on tumour samples between October 2015 and March 2018. PD-L1 test results were matched with patient characteristics using unique identifiers. Concordance between the 28-8 and 22C3 assays was evaluated in matched tumour samples. Data were evaluated across multiple tumour types and in subgroups of patients with lung cancer, melanoma, squamous cell carcinoma of the head and neck, and urothelial carcinoma. RESULTS: 62 180 individual PD-L1 tests were conducted on samples from 55 652 patients. PD-L1 test volume increased ~10-fold over the period evaluated. Test failure rates were typically low, and test turnaround time (TAT) ranged between 2 and 4 days. Concordance between the 28-8 and 22C3 assays was strong in the overall population and across tumour type subgroups (Kendall's tau correlations of 0.94 and 0.92-0.98, respectively). CONCLUSIONS: Test failure rates for PD-L1 tests were low and TAT remained reasonable despite marked increases in test volume. Concordance was high between the 28-8 and 22C3 assays across a range of tumour types and biopsy locations. These findings add to the literature showing high concordance between the 28-8 and 22C3 assays.


Assuntos
Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Imuno-Histoquímica , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/normas , Imuno-Histoquímica/estatística & dados numéricos , Neoplasias/metabolismo , Reprodutibilidade dos Testes
17.
J Cancer Res Ther ; 16(1): 94-97, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362615

RESUMO

Background: The clinicomorphology and immunohistochemical features of T-cell lymphomas have been documented. Aim: The aim of the study was to evaluate the spectrum of clincopathological features of T-cell lymphoma with immunohistochemistry correlation in a tertiary care center. Materials and Methods: The present study was conducted on 19 biopsy specimens received from the Department of Pathology, Kasturba Medical College, from referral hospitals of Mangalore city. Cases of nodal and extranodal T-cell lymphomas diagnosed between January 2012 and December 2015 were selected with evaluation of clinical data, histomorphological features, and immunophenotyping. Appropriate panel of antibodies was chosen after morphological evaluation of the cases. Results: Of the 19 cases of T-cell lymphomas, 14 were nodal disease and 5 were extranodal disease. Among the nodal lymphomas, five were primary peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), four were cases of lymphoblastic lymphoma, three were cases of angioimmunoblastic T-cell lymphomas, and two were cases of anaplastic large-cell lymphoma anaplastic lymphoma kinase (ALK) negative. In extranodal disease, two were mycosis fungoides of skin, one case each of subcutaneous panniculitis-like T-cell lymphoma, T-cell lymphoblastic lymphoma of tonsil, and T-cell lymphoma of the stomach. Conclusions: The diagnosis and subclassification of PTCLs is necessary for therapeutic and prognostic purposes.


Assuntos
Imunofenotipagem/métodos , Linfoma Anaplásico de Células Grandes/patologia , Linfoma de Células T Periférico/patologia , Linfoma de Células T/classificação , Linfoma de Células T/patologia , Centros de Atenção Terciária/estatística & dados numéricos , Adulto , Feminino , Humanos , Imuno-Histoquímica/métodos , Índia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
18.
Cancer Immunol Immunother ; 69(9): 1801-1812, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32350590

RESUMO

Immunotherapy as an approach for cancer treatment is clinically promising. CD73, which is the enzyme that produces extracellular adenosine, favors cancer progression and protects the tumor from immune surveillance. While CD73 has recently been demonstrated to be a potential target for glioma treatment, its role in regulating the inflammatory tumor microenvironment has not yet been investigated. Thus, this study explores the immunotherapeutic value of the CD73 blockade in glioblastoma. The immuno-therapeutic value of the CD73 blockade was evaluated in vivo in immunocompetent pre-clinical glioblastoma model. As such, glioblastoma-bearing rats were nasally treated for 15 days with a siRNA CD73-loaded cationic-nanoemulsion (NE-siRNA CD73R). Apoptosis was determined by flow cytometry using Annexin-V staining and cell proliferation was analyzed by Ki67 expression by immunohistochemistry. The frequencies of the CD4+, CD8+, and CD4+CD25highCD39+ (Treg) T lymphocytes; CD11b+CD45high macrophages; CD11b+CD45low-microglia; and CD206+-M2-like phenotypes, along with expression levels of CD39 and CD73 in tumor and tumor-associated immune cells, were determined using flow cytometry, while inflammatory markers associated with tumor progression were evaluated using RT-qPCR. The CD73 blockade by NE-siRNA CD73 was found to induce tumor cell apoptosis. Meanwhile, the population of Tregs, microglia, and macrophages was significantly reduced in the tumor microenvironment, though IL-6, CCL17, and CCL22 increased. The treatment selectively decreased CD73 expression in the GB cells as well as in the tumor-associated-macrophages/microglia. This study indicates that CD73 knockdown using a nanotechnological approach to perform nasal delivery of siRNA-CD73 to CNS can potentially regulate the glioblastoma immune microenvironment and delay tumor growth by inducing apoptosis.


Assuntos
5'-Nucleotidase/antagonistas & inibidores , 5'-Nucleotidase/imunologia , Proliferação de Células/fisiologia , Glioblastoma/imunologia , Glioblastoma/metabolismo , Glioma/imunologia , Glioma/metabolismo , Adenosina/imunologia , Adenosina/metabolismo , Animais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Imuno-Histoquímica/métodos , Imunoterapia/métodos , Macrófagos/imunologia , Macrófagos/metabolismo , Microglia/imunologia , Microglia/metabolismo , Ratos
19.
Yakugaku Zasshi ; 140(4): 569-576, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32238639

RESUMO

Daptomycin (DAP) has a completely different mechanism of action compared to conventional methicillin-resistant Staphylococcus aureus (MRSA) drugs and is widely used clinically as the first-line drug for the treatment of skin soft tissue infection and sepsis caused by MRSA infection. However, the most serious side effects of DAP include renal dysfunction and rhabdomyolysis. Knowledge of the time sequence of localization of DAP in cells and tissues of animals may help in developing a better understanding of the actual overall pharmacokinetics of DAP. We prepared DAP-specific antibodies by immunizing mice with DAP-GMBS-BSA conjugate. The Anti-DAP antibody was specific for DAP, which enabled us to develop an immunocytochemical method for detecting the uptake of DAP in the rat kidneys. One hour after a single intravenous (i.v.) injection of DAP at 12 mg/kg, immunohistochemical observation showed a strong ring-like positive reaction in the cytoplasm immediately below the microvilli of proximal tubule epithelial cells. The distal tubules and collecting ducts contained DAP-positive and negative cells in the cross section of one tubule. Twenty-four hours after DAP administration, several strong positive reactions of different sizes were observed in the cytoplasm of epithelial cells at the proximal tubule. No staining was detected after 7 days. This study will be a useful tool for analyzing the pharmacokinetics of DAP.


Assuntos
Antibacterianos/metabolismo , Daptomicina/metabolismo , Imuno-Histoquímica/métodos , Rim/metabolismo , Animais , Antibacterianos/administração & dosagem , Daptomicina/administração & dosagem , Infusões Intravenosas , Masculino , Staphylococcus aureus Resistente à Meticilina , Ratos Wistar , Distribuição Tecidual
20.
Oncology ; 98(8): 566-574, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32316005

RESUMO

To identify useful markers for prognostic and therapeutic purposes, The Cancer Genome Atlas (TCGA) provided a molecular classification of gastric cancers (GCs). Previous studies have used immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) to define immunophenotypic surrogate markers of the molecular alterations. Some critical issues concerning the correct definition of immunophenotypic groups have emerged in these studies that employed tissue microarrays (TMAs). We performed an immunophenotypic classification by evaluating MLH1, p53, HER2, E-cadherin, and Epstein-Barr virus (EBV) on the whole section of the surgical GC samples compared to most of the studies conducted on TMAs. We also investigated the immunohistochemical expression of PD-L1, a known therapeutic target. We identified the following immunophenotypic groups: EBV (2.9%); mismatch repair deficient (MMR-D) (7.2%); overexpressed p53 and/or HER2+ (61.4%); aberrant E-cadherin (11.4%); and normal pattern (17.1%). The use of surgical samples emphasized that some immunohistochemical markers were not useful for properly classifying the GC specimens. We can state that EBV (significantly correlated to PD-L1 expression) and MMR-D GCs are well-defined groups, mutually exclusive, and easily assessable with IHC and CISH, and could be candidates for immunotherapy with PD-1/PD-L1 inhibitors. As regards p53, our findings suggest that IHC assessment may be responsible for a misclassification of GC groups. Immunohistochemical evaluation of E-cadherin needs to be standardized, particularly in terms of the heterogeneous cytoplasmic/membranous staining pattern. Whether to consider the normal-pattern group as a separate category remains to be clarified. Because GC specimens with known therapeutic targets account for only 40%, we suggest reviewing the immunophenotypic classification to find new therapeutic targets, such as PD-L1, MLH1, and HER2.


Assuntos
Imuno-Histoquímica/métodos , Fenótipo , Neoplasias Gástricas/classificação , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/metabolismo , Prognóstico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patologia
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