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1.
J Clin Pathol ; 73(2): 102-106, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31462450

RESUMO

AIMS: The cell block technique for assessing endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) specimens from pancreatic mucinous cystic lesions (MCLs) was systematically evaluated for the first time, including comparisons with three traditional methods of assessing such specimens. METHODS: The prospective arm comprised EUS-FNA specimens from EUS-suspected pancreatic MCLs. The retrospective arm comprised EUS-FNA specimens from pancreatic MCLs surgically resected before the study start. For each specimen, these data points were collected: macroscopic likelihood of mucin, cyst fluid carcinoembryonic antigen (CEA) level and presence of mucin in air-dried, direct smears and in cell block preparations. RESULTS: The prospective and retrospective arms of the study comprised 80 and 30 EUS-FNA specimens, respectively. Seven prospective cases led to surgical resections during the study, and therefore, 37 EUS-FNA specimens were confirmed to have originated from MCLs. In the prospective arm, macroscopic mucin was suspected, cyst fluid CEA level exceeded 192 ng/mL, mucin was detected in direct smears and cell block preparations in 78%, 30%, 39% and 73% of cases, respectively. Of the 37 specimens confirmed to originate from MCLs, macroscopic mucin assessment, cyst fluid CEA level, direct smear mucin assessment and cell block mucin assessment had sensitivities for diagnosing MCL of 87%, 45%, 45% and 81%, respectively. CONCLUSIONS: Cell block preparations are as likely to identify mucin from pancreatic MCLs as macroscopic assessment but are twice as likely to diagnose MCL than direct smears and fluid CEA biochemistry. The cell block technique is easy for sample collection and processing especially because these are identical for solid and cystic pancreatic lesions.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Mucinas/análise , Cisto Pancreático/química , Cisto Pancreático/patologia , Inclusão em Parafina , Biomarcadores/análise , Antígeno Carcinoembrionário/análise , Humanos , Cisto Pancreático/cirurgia , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fixação de Tecidos
2.
Zhonghua Bing Li Xue Za Zhi ; 48(10): 779-783, 2019 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-31594042

RESUMO

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions: ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Mucinas/análise , Adulto , Idoso , Biomarcadores Tumorais/análise , Feminino , Humanos , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/genética
3.
Gulf J Oncolog ; 1(30): 13-21, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31242977

RESUMO

BACKGROUND: Chewing Betel (areca-nut) can cause oral cancer. This happens when its components are in direct contact with the oral epithelium. The aim of this study is to understand this mechanism by analyzing salivary mucins, in vitro, during and after betel chewing. METHODS: The in vivo analysis would necessarily involve subtraction of betel to understand its effects. This study analyzed the interaction between mucins and betel in vitro. We added increasing amounts of areca powder, and for comparison an equal amount of pure vine tannin to saliva samples provided by a first volunteer. This study analyzes salivary mucins in two volunteers, one of whom is a regular betel consumer, after chewing the areca-nut, on six saliva samples taken at half-hour intervals. RESULTS: In vitro, total precipitation of the salivary mucins occurs after we added 1g of Areca nut (50 mg Tannin equivalent), a concentration five times lower than what is actually present during the chewing period; in vivo, in the first volunteer, there is a statistically significant increase in the mucins after chewing two and half hours: p-value = 0.02034, while for the regular betel consumer there is a significant decrease: p-value = 0.00512. DISCUSSION: In vitro, we conclude that the polyphenol content in betel causes total precipitation of mucins and causes poor defense of the oral epithelium. The increase of mucins in the non-routine consumers, show a transient (up to two hours after the end of chewing) inflammatory process. Inflammation can cause keratinization of the oral epithelium because the saliva increases its viscosity for the higher amount of mucins, with its lower adherence and protection of the oral cavity. Subsequent and regular consumption of betel nut, as in the regular betel consumer, can cause chronic fibrosis in the oral epithelium and cut the salivary mucins.


Assuntos
Areca/química , Mastigação , Neoplasias Bucais/diagnóstico , Mucinas/análise , Saliva/metabolismo , Adulto , Areca/efeitos adversos , Humanos , Técnicas In Vitro , Masculino , Neoplasias Bucais/etiologia , Neoplasias Bucais/metabolismo , Mucinas/química , Saliva/química
4.
Eur J Histochem ; 63(2)2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31232013

RESUMO

Mucins are of great interest in intestinal research and histochemical methods are often employed to identify them. Since it is in the nature of mucins that they are "hard to hold onto" once they come into contact with water, a frequently used medium in histochemistry, there are a number of challenges that may decrease diagnostic accuracy. As the outcome of methods published for microscopic detection of mucosubstances proved to be unsatisfactory in our hands, the aim was the establishment of a reliable and reproducible protocol. Tissue samples were available from pig feeding experiments. In the present study, we focus on a fixation / staining procedure without making comparisons between differently fed pigs. Several fixation and staining procedures were evaluated for their use in semiautomatic quantification and quality assessment of different mucus fractions simultaneous on one tissue section. Cryostat sectioning, subsequent fixation steps with heat, ethanol and modified Bouin's solution, followed by triple staining with high iron diamine, alcian blue and periodic acid-Schiff turned out to be the best method to identify sulfomucin, sialomucin and neutral mucin simultaneous on one tissue section. This methodology resulted in very good morphology of goblet cells with intact mucin containing vesicles within the cells, which was comparable to ultrastructural electron microscopical observations. Semiautomatic quantification of different mucins was possible. In conclusion, reliable mucus quantification and assessment of mucus quality requires strictly tested procedures. According to our experience, the most important aim after cryosectioning is fast fixation of the mucosubstances, which requires a combination of different fixation steps.


Assuntos
Trato Gastrointestinal/química , Histocitoquímica/métodos , Mucinas/análise , Coloração e Rotulagem/métodos , Animais , Vesículas Citoplasmáticas/química , Trato Gastrointestinal/citologia , Células Caliciformes/química , Células Caliciformes/citologia , Mucinas/química , Mucinas/classificação , Suínos
5.
Mycopathologia ; 184(3): 423-431, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31147870

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) with eosinophilic mucin is considered rare in Korea. The object of this study was to categorize CRS patients with eosinophilic mucin into several groups and compared the groups based on their clinicopathological and radiological features. METHODS: In total, 105 CRS patients with eosinophilic mucin from four tertiary medical centers which are located at Chungcheong province of Korea were included for this study. The patients were divided into four groups for analysis, based on the presence or absence of an allergy (A) to a fungus or fungal element (F) in the mucin. The following were the four groups: allergic fungal rhinosinusitis (AFRS, A+F+), AFRS-like sinusitis (A+F-), eosinophilic fungal rhinosinusitis (EFRS, A-F+), and eosinophilic mucin rhinosinusitis (EMRS, A-F-). Their clinical manifestation, the presence of associated disease, radiological finding, treatment, and treatment outcome were reviewed and compared. RESULTS: There were no patients in the AFRS-like sinusitis group, 47 patients were assigned to the AFRS group, 27 to the EFRS group, and 41 to the EMRS group. Patients of AFRS group showed a significantly higher association with allergic rhinitis than did the other groups. The mean total serum IgE level in the AFRS patients was significantly higher than in the EFRS and EMRS patients. In the AFRS group and EFRS group, 67.6% and 74.1% had unilateral disease, respectively, in contrast to the EMRS group (4.9%). The mean Hounsfield unit values of the area of high attenuation in the AFRS patients were significantly higher than those in the other groups. CONCLUSIONS: Significant clinicopathological differences existed among the subgroups of CRS with eosinophilic mucin. AFRS tends to be an allergic response to colonizing fungi in atopic individuals. In EFRS, local allergies to fungi might play a role in the disease. EMRS is thought to be unconnected with fungal allergies, and it showed different form compared with the AFRS and EFRS groups.


Assuntos
Eosinófilos/imunologia , Mucinas/análise , Micoses/microbiologia , Micoses/patologia , Sinusite/microbiologia , Sinusite/patologia , Tomografia Computadorizada por Raios X , Adulto , Doença Crônica , Feminino , Humanos , Imunoglobulina E/sangue , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico por imagem , Estudos Retrospectivos , Sinusite/diagnóstico por imagem , Resultado do Tratamento
6.
Acta Cir Bras ; 34(4): e201900406, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31038584

RESUMO

PURPOSE: To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine. METHODS: Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%. RESULTS: Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention. CONCLUSION: Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Colo/efeitos dos fármacos , Enema/métodos , Mucosa Intestinal/efeitos dos fármacos , Mesalamina/farmacologia , Mucinas/análise , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite/patologia , Colite/prevenção & controle , Colo/metabolismo , Colo/patologia , Colostomia , Fezes , Trânsito Gastrointestinal , Histocitoquímica , Processamento de Imagem Assistida por Computador , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Mesalamina/uso terapêutico , Mucinas/efeitos dos fármacos , Estresse Oxidativo , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
8.
Prostate ; 79(6): 622-627, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30652335

RESUMO

BACKGROUND: Eosinophilic metaplasia (EM) in the prostate is characterized by the presence of eosinophilic cytoplasmic granules in benign prostatic epithelium. These granules show exocrine-type morphology and positive expression for prostate specific antigen (PSA) and some lysosomal markers. The nature and the full immunohistochemical profile of the granules of EM have not been studied in detail yet. AIM: The aim of the current study is to investigate the expression of epithelial mucins (MUCs) in prostatic epithelium with EM. METHODS: Twenty specimens from transurethral resection of the prostate (TURP) were reviewed for the presence of EM and were stained with Periodic acid-Schiff's procedure with diastase digestion (PAS.D) and immunostained with PSA and MUCs: MUC1, MUC2, MUC5AC, and MUC6. RESULTS: The EM-foci of all prostate glands are PAS.D, PSA positive and show constant immunoreactivity for MUC1. The expression of MUC1 is with membranous and cytoplasmic localization: predominantly apical with membranous accentuation in the cases of EM with large eosinophilic granules, and perinuclear in EM with small eosinophilic granules. There is no expression of other MUCs (MUC2, MUC5AC, and MUC6) in prostatic EM. CONCLUSION: We report for the first time that eosinophilic cytoplasmic granules in prostatic EM are MUC1 positive and can vary in size. Based on our immunohistochemical study we suggest that EM of the prostate is not a form of mucinous metaplasia. The present results enrich the available information about the immunophenotype of EM. We assume that MUC1 might serve as a reliable and constant, although nonspecific, immunohistochemical marker of benign EM-phenotype.


Assuntos
Eosinofilia , Epitélio , Mucina-1/metabolismo , Próstata , Neoplasias da Próstata , Biomarcadores/metabolismo , Epitélio/metabolismo , Epitélio/patologia , Humanos , Imuno-Histoquímica , Masculino , Metaplasia , Pessoa de Meia-Idade , Mucinas/análise , Mucinas/classificação , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
10.
Histopathology ; 74(4): 545-554, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30329165

RESUMO

AIMS: The process of differential diagnosis between epithelioid mesothelioma and lung adenocarcinoma has been progressing; however, there are no absolute immunohistochemical markers with which to definitively diagnose epithelioid mesothelioma. The aim of this study was to search for a novel negative marker of epithelioid mesothelioma. METHODS AND RESULTS: We immunohistochemically studied the applicability of mucin 21 (MUC21), which was identified in our previous study, as a novel, negative diagnostic marker for epithelioid mesothelioma. Seventy epithelioid mesotheliomas and 70 lung adenocarcinomas were investigated for the expression of MUC21, along with other previously reported markers, by the use of immunohistochemistry. MUC21 was expressed in only two of the 70 (3%) epithelioid mesotheliomas, as compared with 67 of the 70 (96%) lung adenocarcinomas. The sensitivity, specificity and accuracy of negative MUC21 expression for differentiating epithelioid mesothelioma from lung adenocarcinoma were 97%, 96%, and 96%, respectively; these are similar to those of carcinoembryonic antigen and claudin-4, and better than those of thyroid transcription factor-1, napsin-A, and mucin 4. CONCLUSION: MUC21 could be used as an additional, novel, negative immunohistochemical marker to differentiate mesothelioma from lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Glicoproteínas de Membrana/biossíntese , Mesotelioma/diagnóstico , Mucinas/biossíntese , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Glicoproteínas de Membrana/análise , Mucinas/análise
11.
Methods Mol Biol ; 1882: 1-8, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30378039

RESUMO

Intraductal papillary mucinous neoplasms (IPMNs) characteristically consist of mucin-filled dilated ducts lined with neoplastic cells forming papillae with a diverse range of morphologies and varying grades of atypia. Based on morphological characteristics and immunohistochemical reaction against mucin proteins, IPMNs are classified into four distinct subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. In this chapter, histomorphological criteria and techniques of immunohistochemical staining and its evaluation for subtyping IPMNs are described.


Assuntos
Biomarcadores Tumorais/análise , Mucinas/análise , Neoplasias Intraductais Pancreáticas/patologia , Biomarcadores Tumorais/metabolismo , Biópsia , Humanos , Imuno-Histoquímica/instrumentação , Imuno-Histoquímica/métodos , Mucinas/metabolismo
12.
Gerodontology ; 36(1): 63-70, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30461050

RESUMO

OBJECTIVES: The aim of this study was to clarify by histopathological examination the origin of oral membranous substances deposited on the palate, tongue, buccal mucosa and teeth. BACKGROUND: Several investigators have reported membranous substances deposited in the mouths of bedridden elderly persons requiring nursing care without oral intake. However, the precise nature and origin of the substances are poorly understood. METHODS: Sixty-nine specimens were taken from the oral cavity of bedridden patients, that is, the palate, dorsum of the tongue, the cheek and teeth. Sections were stained with haematoxylin and eosin stain, alcian-blue and periodic acid-Schiff stain (AB-PAS) and antibodies for pankeratin (AE1AE3) and leukocyte common antigen (LCA). RESULTS: All specimens showed a film-like nature coloured from tan to white, accompanied by a mucous substance. Histologically, specimens of all sites had a similar feature of the combination of basophilic amorphous and eosinophilic lamellar features. The basophilic substance was positive for AB-PAS, and PAS-positive glycogen granules were also noted in the lamellar structure. Immunochemistry revealed various degrees of pankeratin positive substance and LCA-positive inflammatory cell infiltration. CONCLUSION: The oral membranous substance was composed of keratin and mucin with inflammation. These results suggest that the deposition of the oral membranous substance is a pathological condition or oral mucositis caused by dry mouth.


Assuntos
Pessoas Acamadas , Mucosa Bucal/patologia , Palato/patologia , Nutrição Parenteral , Língua/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Queratinas/análise , Masculino , Mucosa Bucal/química , Mucinas/análise , Palato/química , Língua/química , Dente/química , Dente/patologia , Xerostomia/patologia
13.
Anat Rec (Hoboken) ; 301(12): 2128-2144, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30382612

RESUMO

The fundic glands of the stomach contain two types of mucous cells: surface mucous cells (SMCs) located at the surface of the stomach and the pits, and mucous neck cells (MNCs) situated in the neck of the glands. They produce mucins, highly glycosylated proteins. Very little is known about the glycan composition of these mucins and of gastric secretion in general. We used several lectins combined with deglycosylation pretreatments to analyze the glycan composition of SMCs and MNCs. The results showed the presence of terminal sialic acid and subterminal Gal and GalNAc, which is consistent with previous knowledge about glycosylation in mucins. Our results also support previous reports that showed a different expression of mucins in the SMCs, depending on their superficial or deep location in the pit. Some lectins labeled only the perinuclear region of the SMCs, but not the apical region, where the secretory granules are stored. This suggests that the lectins are labeling sugar residues that are accessible to lectins during the first steps of glycan synthesis, which occurs in the endoplasmic reticulum and Golgi apparatus. Our results indicate that SMCs and MNCs produce a mucus secretion with a different glycoconjugate composition. The secretion is more varied in SMCs. As our results coincide with what we know about glycosylation of mucins, we can conclude that most of the glycans detected belong to mucins, and the differences in glycosylation observed in each cell type may be due, mainly, to the different secreted mucins. Anat Rec, 301:2128-2144, 2018. © 2018 Wiley Periodicals, Inc.


Assuntos
Fundo Gástrico/citologia , Fundo Gástrico/metabolismo , Mucosa Gástrica/citologia , Mucosa Gástrica/metabolismo , Glicoconjugados/metabolismo , Muco/metabolismo , Animais , Fundo Gástrico/química , Mucosa Gástrica/química , Glicoconjugados/análise , Masculino , Mucinas/análise , Mucinas/metabolismo , Muco/química , Ratos , Ratos Sprague-Dawley
14.
Am J Surg Pathol ; 42(11): 1419-1428, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30138216

RESUMO

"Mucoepidermoid carcinoma (MEC)" has been accepted as a synonym for pancreatic adenosquamous carcinoma (ASC). Pancreatic ASC can show salivary gland-type MEC-like morphology. CRTC1/3-MAML2 fusion gene is a characteristic molecular feature of MEC of the salivary gland. We conducted this study to clarify whether the pancreatic ASC with salivary gland-type MEC-like morphology (Pan-MEC) is a pancreatic counterpart of salivary gland-type MEC (Sal-MEC). We retrospectively analyzed 37 pancreatic ASCs including 16 Pan-MECs and 21 tumors without MEC-like features (ASC-NOS [not otherwise specified]), and we investigated (1) clinicopathologic features, (2) the presence of CRTC1/3-MAML2 fusion gene by reverse transcription polymerase chain reaction, (3) the presence of rearrangement of MAML2 gene by fluorescence in situ hybridization, and (4) mucin core proteins by immunohistochemistry. We also compared 16 Pan-MECs with 20 Sal-MECs by immunohistochemistry for mucin core protein. There were no significant differences of any clinicopathologic characteristics and survival analysis between the Pan-MECs and ASCs-NOS. Of note, the pancreatic ASCs (including Pan-MEC and ASC-NOS) were significantly more aggressive than conventional pancreatic ductal adenocarcinoma. In addition, all Pan-MECs were histologically high-grade. CRTC1/3-MAML2 fusion gene and MAML2 gene rearrangement were not detected in any ASCs including Pan-MECs. There were significant differences of MUC5AC and MUC6 between the Pan-MECs and Sal-MECs, but no significant differences of mucin core protein between the Pan-MECs and pancreatic ASCs-NOS. Pan-MEC is histologically and biologically high-grade and unrelated to CRTC1/3-MAML2 fusion gene, unlike Sal-MEC which is related to CRTC1/3-MAML2 fusion gene. Pan-MEC is not a pancreatic counterpart of CRTC1/3-MAML2 fusion gene-related Sal-MEC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Adenoescamoso/genética , Carcinoma Mucoepidermoide/genética , Proteínas de Ligação a DNA/genética , Fusão Gênica , Proteínas Nucleares/genética , Neoplasias Pancreáticas/genética , Neoplasias das Glândulas Salivares/genética , Fatores de Transcrição/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , Carcinoma Adenoescamoso/química , Carcinoma Adenoescamoso/classificação , Carcinoma Adenoescamoso/patologia , Carcinoma Mucoepidermoide/química , Carcinoma Mucoepidermoide/classificação , Carcinoma Mucoepidermoide/patologia , Feminino , Rearranjo Gênico , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mucinas/análise , Gradação de Tumores , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/classificação , Neoplasias Pancreáticas/patologia , Fenótipo , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias das Glândulas Salivares/química , Neoplasias das Glândulas Salivares/classificação , Neoplasias das Glândulas Salivares/patologia , Terminologia como Assunto
15.
Biosensors (Basel) ; 8(3)2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30134577

RESUMO

The viscosity variation of sputum is a common symptom of the progression of Chronic Obstructive Pulmonary Disease (COPD). Since the hydration of the sputum defines its viscosity level, dielectric sensors could be used for the characterization of sputum samples collected from patients for early diagnosis of COPD. In this work, a CMOS-based dielectric sensor for the real-time monitoring of sputum viscosity was designed and fabricated. A proper packaging for the ESD-protection and short-circuit prevention of the sensor was developed. The performance evaluation results show that the radio frequency sensor is capable of measuring dielectric constant of biofluids with an accuracy of 4.17%. Integration of this sensor into a portable system will result in a hand-held device capable of measuring viscosity of sputum samples of COPD-patients for diagnostic purposes.


Assuntos
Técnicas Biossensoriais/métodos , Mucinas/análise , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Semicondutores , Escarro/química , Viscosidade , Técnicas Biossensoriais/instrumentação , Diagnóstico Precoce , Humanos
16.
Yonsei Med J ; 59(5): 633-642, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29869461

RESUMO

PURPOSE: To investigate the effects of Helicobacter pylori (H. pylori)-CagA and the urease metabolite NH4⁺ on mucin expression in AGS cells. MATERIALS AND METHODS: AGS cells were transfected with CagA and/or treated with different concentrations of NH4CL. Mucin gene and protein expression was assessed by qPCR and immunofluorescence assays, respectively. RESULTS: CagA significantly upregulated MUC5AC, MUC2, and MUC5B expression in AGS cells, but did not affect E-cadherin and MUC6 expression. MUC5AC, MUC6, and MUC2 expression in AGS cells increased with increasing NH4⁺ concentrations until reaching a peak level at 15 mM. MUC5B mRNA expression in AGS cells (NH4⁺ concentration of 15 mM) was significantly higher than that at 0, 5, and 10 mM NH4⁺. No changes in E-cadherin expression in AGS cells treated with NH4⁺ were noted, except at 20 mM. The expression of MUC5AC, MUC2, and MUC6 mRNA in CagA-transfected AGS cells at an NH4⁺ concentration of 15 mM was significantly higher than that at 0 mM, and decreased at higher concentrations. The expression of MUC5B mRNA increased with increases in NH4⁺ concentration, and was significantly higher compared to that in untreated cells. No significant change in the expression of E-cadherin mRNA in CagA-transfected AGS cells was observed. Immunofluorescence assays confirmed the observed changes. CONCLUSION: H. pylori may affect the expression of MUC5AC, MUC2, MUC5B, and MUC6 in AGS cells via CagA and/or NH4⁺, but not E-cadherin.


Assuntos
Infecções por Helicobacter/genética , Helicobacter pylori/patogenicidade , Mucina-5AC/genética , Mucinas/biossíntese , Neoplasias Gástricas/genética , Urease/metabolismo , Fatores de Virulência , Compostos de Amônio , Antígenos de Bactérias , Proteínas de Bactérias , Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/virologia , Helicobacter pylori/metabolismo , Humanos , Mucina-5AC/análise , Mucina-5AC/biossíntese , Mucina-5AC/metabolismo , Mucina-2/análise , Mucina-2/biossíntese , Mucina-6/análise , Mucina-6/biossíntese , Mucinas/análise , Mucinas/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/virologia , Urease/genética , Virulência
17.
Am J Surg Pathol ; 42(8): 989-1000, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29851704

RESUMO

The International Endocervical Adenocarcinoma Criteria and Classification was developed to separate endocervical adenocarcinomas (ECAs) into 2 main categories on the basis of morphology such as human papilloma virus-associated (HPVA) and non-human papilloma virus-associated adenocarcinomas. We aimed to improve the diagnostic accuracy of International Endocervical Adenocarcinoma Criteria and Classification by performing a comprehensive immunohistochemical evaluation and constructing objective immunohistochemical-based algorithms for the classification of these tumors. Tissue microarrays were constructed from 297 of 409 cases used to develop the original classification. Immunostains included p16, p53, estrogen receptor (ER), progesterone receptor, androgen receptor, Vimentin, CK7, CK20, HER2, HIK1083, MUC6, CA-IX, SATB2, HNF-1beta, napsin A, PAX8, CDX2, GATA3, p63, p40, and TTF-1. High-risk human papilloma virus (HR-HPV) was detected by in situ hybridization (ISH) using probes against E6 and E7 mRNA expressed in 18 different virus types. Vimentin, ER, and progesterone receptor were expressed in a significant minority of ECAs, mostly HPVAs, limiting their use in differential diagnosis of endometrioid carcinoma when unaccompanied by HPV-ISH or p16. HR-HPV ISH had superior sensitivity, specificity, and negative and positive predictive values compared with p16, as published previously. HNF-1beta did not have the anticipated discriminatory power for clear cell carcinoma, nor did MUC6 or CA-IX for gastric-type carcinoma. HNF-1beta and napsin A were variably expressed in clear cell carcinoma, with HNF-1beta demonstrating less specificity, as it was ubiquitously expressed in gastric-type carcinoma and in the majority of HPV-associated mucinous (predominantly intestinal-type and invasive ECA resembling stratified mucin-producing intraepithelial lesion [iSMILE]) and usual-type carcinomas. HIK1083 was expressed in nearly half of gastric-type carcinomas, but not in the vast majority of other subtypes. GATA3 was positive in 10% of usual-type adenocarcinomas and in single examples of other subtypes. Rare gastric-type and HPVA mucinous carcinomas displayed HER2 overexpression. Androgen receptor was positive in 6% of usual-type adenocarcinomas. Aberrant p53 expression was found in only 3.6% of usual-type HPVA carcinomas, but it was more prevalent in mucinous (intestinal type and iSMILE) HPVAs and non-human papilloma virus-associates (particularly in gastric-type carcinoma, >50% of cases). The following diagnostic classification algorithms were developed with the above data. Carcinomas without overt cytoplasmic mucin (endometrioid, usual-type endocervical, clear cell, and mesonephric carcinomas) can be subclassified using HR-HPV ISH, ER, and GATA3, whereas carcinomas with easily appreciated cytoplasmic mucin (endometrioid carcinoma with mucinous features, HPVA mucinous, and gastric-type carcinomas) can be subclassified with HR-HPV ISH and ER.


Assuntos
Adenocarcinoma/química , Algoritmos , Biomarcadores Tumorais/análise , Imuno-Histoquímica , Neoplasias do Colo do Útero/química , Adenocarcinoma/classificação , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Europa (Continente) , Feminino , Fator de Transcrição GATA3/análise , Humanos , Hibridização In Situ , Mucinas/análise , Invasividade Neoplásica , América do Norte , Papillomaviridae/genética , Valor Preditivo dos Testes , RNA Viral/genética , Receptores Estrogênicos/análise , Reprodutibilidade dos Testes , Análise Serial de Tecidos , Proteína Supressora de Tumor p53/análise , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
18.
Am J Surg Pathol ; 42(8): 1010-1026, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29846186

RESUMO

We have identified 25 lesions involving alveolar lung parenchyma characterized by nodular proliferation of bland bilayered bronchiolar-type epithelium containing a continuous layer of basal cells. These lesions shared some histologic features with the recently described entity of ciliated muconodular papillary tumor (CMPT); however, the majority did not fit all diagnostic criteria in that they exhibited only focal or absent papillary architecture, and they had variable number of ciliated and mucinous cells, with some lesions entirely lacking 1 or both of these components. The morphologic and immunohistochemical features ranged from those resembling proximal bronchioles (proximal-type: moderate to abundant mucinous and ciliated cells; negative or weak TTF1 in luminal cells; n=8) to those resembling respiratory bronchioles (distal-type: scant or absent mucinous and ciliated cells; positive TTF1 in luminal cells; n=17). The hallmark of all lesions was a continuous layer of basal cells (p40 and CK5/6-positive). We provisionally designated these lesions as bronchiolar adenomas (BAs) and analyzed their clinicopathologic and molecular features. All BAs were discrete, sharply circumscribed lesions with a median size of 0.5 cm (range, 0.2 to 2.0 cm). Most lesions were either entirely flat (n=14) or contained focal papillary architecture (n=7); only 4 lesions, all proximal-type, were predominantly papillary, fitting the classic description of CMPT. Notably, of 9 lesions submitted for frozen section evaluation, 7 were diagnosed as adenocarcinoma. No postsurgical recurrences were observed for any lesions (median follow-up, 11 mo). Twenty-one BAs underwent next-generation sequencing and/or immunohistochemistry for BRAF V600E, revealing mutation profiles similar to those previously described for CMPTs, including BRAF V600E mutations (n=8, 38%), unusual EGFR exon 19 deletions (n=2, 10%), EGFR exon 20 insertions (n=2, 10%), KRAS mutations (n=5, 24%), and HRAS mutations (n=1, 5%). The mutation profiles were similar in proximal-type and distal-type lesions. In conclusion, we describe a family of putatively benign clonal proliferations with a spectrum of morphology recapitulating various levels of the bronchiolar tree, of which only a minor subset fits the classic description of CMPT. Comparable mutation profiles and partially overlapping morphologic features across the spectrum of these lesions support their nosological relationship. We propose designating this entire family of lesions as BAs, and that lesions currently designated CMPTs represent a subgroup of this family.


Assuntos
Adenoma/diagnóstico , Biomarcadores Tumorais , Análise Mutacional de DNA , Imuno-Histoquímica , Imunofenotipagem/métodos , Neoplasias Pulmonares/diagnóstico , Nódulos Pulmonares Múltiplos/diagnóstico , Mutação , Adenoma/genética , Adenoma/imunologia , Adenoma/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Proliferação de Células , China , Cílios/patologia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mucinas/análise , Nódulos Pulmonares Múltiplos/genética , Nódulos Pulmonares Múltiplos/imunologia , Nódulos Pulmonares Múltiplos/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Terminologia como Assunto , Estados Unidos
19.
Clin Chem Lab Med ; 56(11): 1945-1953, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-29768245

RESUMO

BACKGROUND: Mucin 13 (MUC13) is a cell surface glycoprotein aberrantly expressed in a variety of epithelial carcinomas. Thus far, the role of MUC13 in various diseases remains elusive. To the best of our knowledge, this is the first study to examine the potential of MUC13 as a serum biomarker in a variety of carcinomas and other conditions. METHODS: We developed a recombinant MUC13 protein, mouse monoclonal antibodies and enzyme immunoassay (ELISA) for MUC13. We used this assay to measure MUC13 levels in the supernatants of cancer cell lines and a large cohort of serum samples from healthy and diseased individuals. RESULTS: MUC13 is secreted from cancer cell lines, with highest levels found in ovarian cancer cell lines. MUC13 levels in human sera were significantly increased in patients with renal failure and 20%-30% of patients with ovarian, liver, lung and other cancers. MUC13 was also elevated in 70% of patients with active cutaneous melanoma, but not uveal melanoma. Furthermore, we identified significant MUC13 elevations in the serum of patients with vasculitis (ANCA-positive) autoantibodies, but not in those with inflammatory bowel disease. CONCLUSIONS: Serum MUC13 is frequently elevated not only in a variety of malignant cases but also in some benign pathologies, thus appearing to be a non-specific disease biomarker. Nonetheless, serum MUC13 is clearly highly elevated in some carcinoma patients, and its relationship with tumor progression in this context warrant further research. Future studies that examine the correlation between serum MUC13 levels to stage of cancer could elucidate prognostic potential.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Mucinas/análise , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/metabolismo , Mucinas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/metabolismo
20.
Am J Surg Pathol ; 42(7): 918-926, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29697438

RESUMO

Risk stratification of patients with Barrett's esophagus (BE) is based on diagnosis of low-grade dysplasia (LGD). LGD has a poor interobserver agreement and a limited value for prediction of progression to high-grade dysplasia or esophageal adenocarcinoma. Specific reproducible histologic criteria may improve the predictive value of LGD. Four gastrointestinal pathologists examined 12 histologic criteria associated with LGD in 84 BE patients with LGD (15 progressors and 69 nonprogressors). The criteria with at least a moderate (kappa, 0.4 to 0.6) interobserver agreement were validated in an independent cohort of 98 BE patients with LGD (30 progressors and 68 nonprogressors). Hazard ratios (HR) were calculated by Cox proportional hazard regression analysis using time-dependent covariates correcting for multiple endoscopies during follow-up. Agreement was moderate or good for 4 criteria, that is, loss of maturation, mucin depletion, nuclear enlargement, and increase of mitosis. Combination of the criteria differentiated high-risk and low-risk group amongst patients with LGD diagnosis (P<0.001). When ≥2 criteria were present, a significantly higher progression rate to high-grade dysplasia or esophageal adenocarcinoma was observed (discovery set: HR, 5.47; 95% confidence interval [CI], 1.81-17; P=0.002; validation set: HR, 3.52; 95% CI, 1.56-7.97; P=0.003). Implementation of p53 immunohistochemistry and histologic criteria optimized the prediction of progression (area under the curve, 0.768; 95% CI, 0.656-0.881). We identified and validated a clinically applicable panel of 4 histologic criteria, segregating BE patients with LGD diagnosis into defined prognostic groups. This histologic panel can be used to improve clinical decision making, although additional studies are warranted.


Assuntos
Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/patologia , Esofagoscopia , Esôfago/patologia , Adenocarcinoma/química , Idoso , Esôfago de Barrett/metabolismo , Biópsia , Tamanho do Núcleo Celular , Progressão da Doença , Neoplasias Esofágicas/química , Esôfago/química , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mitose , Mucinas/análise , Variações Dependentes do Observador , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Proteína Supressora de Tumor p53/análise
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