RESUMO
BACKGROUND: The present study was based on the null hypothesis that there is no difference in clinicoradiographic parameters and whole salivary alpha amylase (AA) and mucin-4 levels before and after non-surgical mechanical debridement (NSMD) of patients with peri-implant mucositis (PM). The aim was to assess whole salivary AA and mucin-4 levels before and after treatment of PM. METHODS: Patients with PM (Group-1) and individuals without peri-implant diseases (Group-2) were included. Demographic data was collected and peri-implant modified plaque and bleeding indices (mPI and mBI, respectively), probing depth (PD) and crestal bone loss were measured at baseline. Levels of AA and mucin-4 were assessed in unstimulated whole saliva samples. All patients underwent full-mouth non-surgical periodontal therapy (NSPT) and NSMD; and clinical parameters and salivary biomarkers were re-assessed after 3 months. Level of significance was set at P < 0.01. RESULTS: Twenty-six and 32 individuals were included in groups 1 and 2, respectively. None of the participants had periodontitis. At baseline clinical periodontal parameters (PI [P < 0.001], GI [P < 0.001], clinical AL [P < 0.001] and PD [P < 0.001]) were significantly high in Group-1 than Group-2. At 3-month follow-up, there was a statistically significant reduction in clinical periodontal and peri-implant parameters (PI [P < 0.01], GI [P < 0.01], and PD [P < 0.01]) in Group-1 compared with their baseline values. At baseline, salivary AA levels were significantly high in Group-1 than Group-2 (P < 0.01). At 3-month follow-up, there was no significant difference in whole salivary AA levels among patients in groups 1 and 2. CONCLUSIONS: The AA and mucin-4 levels are potential biomarkers for evaluation of peri-implant diseases including PM. Mechanical instrumentation continues to be the most predictable treatment option for the management of peri-implant diseases.
Assuntos
Implantes Dentários , Mucina-4 , Peri-Implantite , Saliva , alfa-Amilases Salivares , Estomatite , Biomarcadores/análise , Desbridamento , Implantes Dentários/efeitos adversos , Humanos , Mucina-4/análise , Mucosite/etiologia , Mucosite/metabolismo , Mucosite/terapia , Peri-Implantite/etiologia , Peri-Implantite/metabolismo , Peri-Implantite/terapia , Saliva/química , alfa-Amilases Salivares/análise , Estomatite/etiologia , Estomatite/metabolismo , Estomatite/terapiaRESUMO
MUC1 and MUC4 are two transmembranous proteins, which have been seen to express aberrantly in various human neoplasms and advocated as independent prognostic markers. Till now no extensive studies have been carried out on combined expression of MUC1 and MUC4 in oral leukoplakia and Oral squamous cell carcinoma. This study is an endeavour to evaluate Immunohistochemical coexpression of MUC1 and MUC4 in Oral Leukoplakia and Oral squamous cell carcinoma and furthr establish them as prognostic markers. Immunohistochemical analysis of MUC1 and MUC4 was done on 24 cases of Oral squamous cell carcinoma, 24 cases of leukoplakia and 12 normal oral mucosal tissues. Chi square test and one way ANOVA test were employed for statistical analysis. Normal oral mucosa and leukoplakia group showed higher frequency of negative immunoexpression compared to oral squamous cell carcinoma group. Furthur in Oral squamous cell carcinoma group, higher frequency of double positive coexpression in well and moderately differentiated oral squamous cell carcinoma and single positive coexpression in poorly differentiated oral squamous cell carcinoma was obtained. A definite rise of immunoexpression of MUC1 and MUC4 was observed from normal oral mucosa to leukoplakia to oral squamous cell carcinoma indicative of their contribution as diagnostic and prognostic markers.
Assuntos
Biomarcadores Tumorais/análise , Leucoplasia Oral , Mucina-1/biossíntese , Mucina-4/biossíntese , Carcinoma de Células Escamosas de Cabeça e Pescoço , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Leucoplasia Oral/diagnóstico , Leucoplasia Oral/metabolismo , Leucoplasia Oral/patologia , Masculino , Pessoa de Meia-Idade , Mucina-1/análise , Mucina-4/análise , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
AIMS: Secretory carcinoma (SC) (synonym: mammary analogue secretory carcinoma) is a low-grade salivary gland tumour that occurs in both major and minor salivary glands. SC is known for its wide morphological, architectural and immunohistochemical spectrum, which overlaps with those of several salivary gland neoplasms, including acinic cell carcinoma (AciCC) and intercalated duct-type intraductal carcinoma (IDC) in major salivary glands, and polymorphous adenocarcinoma (PAC) in minor salivary glands. These tumours share with SC some morphological features and SOX10 immunoreactivity; also, with the exception of AciCC, they all coexpress S100 and mammaglobin. METHODS AND RESULTS: We compared MUC4 and mammaglobin expression in 125 salivary gland carcinomas (54 genetically confirmed SCs, 20 AciCCs, 21 PACs, and 30 IDCs) to evaluate the potential of these two markers to differentiate these entities. Moderate to strong diffuse MUC4 positivity was detected in 49 SCs (90.7%), as compared with none of the IDCs and PACs. In contrast, mammaglobin was frequently expressed in SCs (30 of 36 cases; 83.3%), IDCs (24/28; 85.7%), and PACs (7/19; 36.8%). Two of three high-grade SCs lost MUC4 expression in the high-grade tumour component. No significant correlation was found between MUC4 expression and the fusion variant in SC (ETV6-NTRK versus non-ETV6-NTRK). CONCLUSION: The results of our study identify MUC4 as a sensitive (90.7%) and specific (100%) marker for SC, with high positive (100%) and negative (93.4%) predictive values. Thus, MUC4 may be used as a surrogate for SC in limited biopsy material and in cases with equivocal morphology.
Assuntos
Diagnóstico Diferencial , Carcinoma Secretor Análogo ao Mamário/diagnóstico , Mucina-4/análise , Neoplasias das Glândulas Salivares , Biomarcadores Tumorais/análise , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma de Células Acinares/diagnóstico , Carcinoma de Células Acinares/patologia , Humanos , Mamoglobina A/metabolismo , Carcinoma Secretor Análogo ao Mamário/metabolismo , Carcinoma Secretor Análogo ao Mamário/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologiaRESUMO
Among pancreatic intraductal papillary neoplasms, gastric, intestinal, and pancreatobiliary intraductal papillary mucinous neoplasm (IPMN), intraductal oncocytic papillary neoplasm (IOPN), and intraductal tubulopapillary neoplasm (ITPN) have been defined, differing regarding association with invasive carcinoma and prognosis. Immunohistochemistry (IHC) can help in the distinction of these neoplasms, but a proportion is unclassifiable using recommended markers. Hence, additional markers useful for the typing of pancreatic intraductal papillary neoplasms are needed. The reported frequencies of the different types of IPMNs in surgical series vary to some extent, and such data based on Danish patients are currently lacking. Besides, the role of mismatch repair (MMR) deficiency in these neoplasms has not been fully elucidated. We aimed to evaluate the frequency of different types of pancreatic intraductal papillary neoplasms in a Danish cohort. Furthermore, we aimed to examine the utility of CD117, CK17, CK20, MUC4, and villin as markers for their distinction, in addition to the recommended markers MUC1, MUC2, MUC5AC, MUC6 and CDX2, and to evaluate the frequency of MMR deficiency. We typed 40 consecutively resected pancreatic intraductal papillary neoplasms according to the WHO criteria from 2019. IHC for CD117, CDX2, CK17, CK20, MLH1, MSH2, MSH6, MUC1 (H23), MUC1 (Ma695), MUC2, MUC4, MUC5AC, MUC6, PMS2, and villin was performed and evaluated using a five-tiered semiquantitative scale. A subset of the tumours was examined with PCR for microsatellite instability (MSI). Most tumours were intestinal (40 %) and gastric (40 %) IPMNs, followed by pancreatobiliary (17 %) IPMNs and IOPN (3 %). All cases were MMR proficient. We found a higher expression of MUC4, CK20 and villin in intestinal compared to gastric IPMNs (p < 0.01, p < 0.001 and p < 0.001). MUC4 was more strongly expressed in intestinal compared to pancreatobiliary IPMNs, while the opposite was found for CK17 (p < 0.05 and p < 0.05). IOPN showed strong CD117 expression (score 4), while all gastric IPMNs were negative and 50 % and 29 % of intestinal and pancreatobiliary IPMNs only showed weak expression (score 1). Our data suggest that CK20, MUC4 and villin may aid in the identification of intestinal IPMNs, while CK17 and CD117 may aid in the identification of pancreatobiliary IPMNs and IOPN, in some cases. However, additional studies evaluating these markers in pancreatic intraductal papillary neoplasms are needed.
Assuntos
Biomarcadores Tumorais/análise , Reparo de Erro de Pareamento de DNA , Queratina-17/análise , Proteínas dos Microfilamentos/análise , Mucina-4/análise , Neoplasias Intraductais Pancreáticas/química , Neoplasias Pancreáticas/química , Proteínas Proto-Oncogênicas c-kit/análise , Idoso , Dinamarca , Feminino , Humanos , Imuno-Histoquímica , Queratina-20/análise , Masculino , Pessoa de Meia-Idade , Neoplasias Intraductais Pancreáticas/genética , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Intraductais Pancreáticas/cirurgia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Valor Preditivo dos Testes , Sistema de RegistrosRESUMO
Vitreo-retinal (VR) surgeries induce conjunctival changes. However, there are no study reports regarding prevalence and severity of dry eye after these surgeries. This study evaluated dry eye outcome after VR surgery. Patients undergoing VR surgery classified as scleral buckle and microincision vitrectomy surgery (n = 44, mean age: 56.09±10.2 years) were recruited. Dry eye evaluation was done before and 8 weeks after surgery (2 weeks after omitting topical eye drops). Conjunctival imprint cytology for goblet cell count and tear Mucin 5AC (MUC5AC) protein estimation was done. Gene expressions of MUC5AC, MUC4, MUC16, Aquaporin 4 (AQP4) and AQP5 were analyzed in the conjunctival imprint cells by qPCR. None of the patients exhibited clinical signs of dry eye after VR surgery. But the conjunctival goblet cell density (GCD) was significantly lowered post-VR surgery (63% cases, **p = 0.012) with no alterations in the tear MUC5AC protein. Post-VR surgery, the conjunctival cell gene expression of MUC4, MUC16 and AQP4 were significantly increased (*p = 0.025, *p = 0.05 and *p = 0.02 respectively) and AQP5 was significantly lowered (*p = 0.037), with no change in MUC5AC expression. Tear cytokines were significantly increased post-VR surgery (anti-inflammatory: IL1RA, IL4, IL5, IL9, FGF; PDGFbb and pro-inflammatory: IL2, IL6, IL15, GMCSF and IFNg). Though clinical signs of dry eye were not observed after VR surgery, ocular surface changes in the form of reduced GCD, altered MUC5AC, MUC4, MUC16, AQP4, AQP5 and cytokines are suggestive of dry eye outcome at the molecular level especially inpatients aged above 51 years, especially female gender and those who are diabetic.
Assuntos
Aquaporinas/genética , Síndromes do Olho Seco/cirurgia , Mucinas/genética , Aquaporina 4/análise , Aquaporina 4/genética , Aquaporina 5/análise , Aquaporina 5/genética , Aquaporinas/análise , Antígeno Ca-125/análise , Antígeno Ca-125/genética , Túnica Conjuntiva/química , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Síndromes do Olho Seco/genética , Síndromes do Olho Seco/patologia , Feminino , Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mucina-5AC/análise , Mucina-5AC/genética , Mucina-4/análise , Mucina-4/genética , Mucinas/análise , Lágrimas/química , Lágrimas/metabolismoRESUMO
Gastric adenocarcinoma develops in metaplastic mucosa associated with Helicobacter pylori infection in the stomach. We have sought to evaluate the precise lineage changes in the stomachs of insulin-gastrin (INS-GAS) mice infected with H. pylori and/or intestinal flora (Altered Schaedler's Flora; ASF). Stomachs from groups infected with H. pylori contained progressive spasmolytic polypeptide-expressing metaplasia (SPEM) compared with germ-free and mice infected with ASF alone. The overall phenotype of the H. pylori-infected mice was dominated by Ulex europaeus lectin (UEAI)-positive foveolar hyperplasia that was distinct from GSII/CD44v9-positive SPEM. However, in the mice with H. pylori co-infected with ASF, we identified a subpopulation of UEAI-positive foveolar cells that co-expressed intestinal mucin 4 (MUC4). These regions of foveolar cells were variably positive for CD44v9 as well as TFF3. Interestingly, an intravascular lesion identified in a dual H. pylori/ASF-infected mouse expressed both UEAI and Muc4. Finally, we identified an increase in the number of tuft cells within the mucosa of H. pylori-infected groups. Our findings suggest that H. pylori infection promotes foveolar hyperplasia as well as metaplasia, while co-infection may promote progressive foveolar and metaplastic lesions as well as dysplasia. Grading of gastric lesions in mice as preneoplastic requires multiple immunostaining markers to assign lineage derivation and behavior.
Assuntos
Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Animais , Quinases Semelhantes a Duplacortina , Mucosa Gástrica/microbiologia , Microbioma Gastrointestinal , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Receptores de Hialuronatos/análise , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/análise , Masculino , Camundongos , Mucina-4/análise , Proteínas Serina-Treonina Quinases/análise , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologiaRESUMO
In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma Mucoepidermoide/patologia , Mucina-4/biossíntese , Mucina-6/biossíntese , Neoplasias das Glândulas Salivares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Mucoepidermoide/metabolismo , Carcinoma Mucoepidermoide/mortalidade , Criança , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mucina-4/análise , Mucina-6/análise , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/mortalidade , Transcriptoma , Adulto JovemRESUMO
Sarcomatoid mesothelioma, a histological subtype of malignant pleural mesothelioma, is a very aggressive tumor with a poor prognosis. Histological diagnosis of sarcomatoid mesothelioma largely depends on the histomorphological feature of spindled tumor cells with immunohistochemical reactivity to cytokeratins. Diagnosis also requires clinico-radiological and/or macroscopic evidence of an extrapulmonary location to differentiate it from lung sarcomatoid carcinoma. Although there are promising immunohistochemical antibody panels to differentiate mesothelioma from lung carcinoma, a consensus on the immunohistochemical markers that distinguish sarcomatoid mesothelioma from lung sarcomatoid carcinoma has not been reached and requires further study. We performed whole gene expression analysis of formalin-fixed paraffin-embedded tissue from sarcomatoid mesothelioma and lung sarcomatoid carcinoma and observed significant differences in the expression of MUC4 and other genes between sarcomatoid mesothelioma and lung sarcomatoid carcinoma. Immunohistochemistry demonstrated that MUC4 was expressed in the spindled tumor cells of lung sarcomatoid carcinoma (21/29, 72%) but was not expressed in any sarcomatoid mesothelioma (0/31, 0%). To differentiate sarcomatoid mesothelioma from lung sarcomatoid carcinoma, negative MUC4 expression showed 100% sensitivity and 72% specificity and accuracy rate of 87%, which is higher than immunohistochemical markers such as calretinin, D2-40 and Claudin-4. Therefore, we recommend to include MUC4 as a novel and useful negative immunohistochemical marker for differentiating sarcomatoid mesothelioma from lung sarcomatoid carcinoma.
Assuntos
Carcinoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Mucina-4/biossíntese , Neoplasias Pleurais/diagnóstico , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Perfilação da Expressão Gênica/métodos , Humanos , Imuno-Histoquímica , Mesotelioma Maligno , Mucina-4/análise , Sensibilidade e EspecificidadeRESUMO
AIM: Periodontitis is a chronic inflammatory disease, characterized by irreversible destruction of tooth-supporting tissue including alveolar bone. We recently reported mucin 4 (MUC4) and matrix metalloproteinase 7 (MMP7) as highly associated with periodontitis in gingival tissue biopsies. The aim of this study was to further investigate the levels of MUC4 and MMP7 in saliva and gingival crevicular fluid (GCF) samples of patients with periodontitis. MATERIALS AND METHODS: Saliva and GCF samples were collected from periodontitis patients and healthy controls. The levels of MUC4, MMP7, and total protein concentrations were analysed using ELISA or Bradford assay. RESULTS: MUC4 levels were significantly lower in saliva and GCF from periodontitis patients relative to healthy controls. MMP7 levels were significantly higher in saliva and GCF from periodontitis patients. Multivariate analysis revealed that MUC4 was significantly associated with periodontitis after adjusting for age and smoking habits and, moreover, that the combination of MUC4 and MMP7 accurately discriminated periodontitis from healthy controls. CONCLUSIONS: MUC4 and MMP7 may be utilized as possible novel biomarkers for periodontitis.
Assuntos
Líquido do Sulco Gengival/química , Metaloproteinase 7 da Matriz/análise , Mucina-4/análise , Periodontite/diagnóstico , Saliva/química , Adulto , Biomarcadores/análise , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We report the case of a 34-year-old woman presenting a 10cm axillary mass diagnosed as hybrid tumor low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma. Microbiopsy for morphological and immunohistochemical analyses was associated with molecular analysis (FISH and PCR) to confirm the diagnosis.
Assuntos
Fibrossarcoma/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Axila , Proteínas de Ligação a Calmodulina/análise , Terapia Combinada , Feminino , Fibrossarcoma/química , Fibrossarcoma/diagnóstico , Fibrossarcoma/terapia , Humanos , Mucina-4/análise , Proteínas de Neoplasias/análise , Neoplasias Primárias Múltiplas/química , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/terapia , Proteína EWS de Ligação a RNA , Proteína FUS de Ligação a RNA/análise , Proteínas de Ligação a RNA/análise , Radioterapia Adjuvante , Neoplasias de Tecidos Moles/química , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/terapiaRESUMO
PURPOSE: Implant placement entails disruption of the epithelial continuity, which can lead to various complications. Therefore, the area of mucosal penetration is of particular interest clinically. The goal of the present study was to compare gene expression in peri-implant soft tissue (PIST) with that in oral mucosal tissue (OMT) using microarray analysis, and to investigate which genes were specifically expressed in PIST. MATERIALS AND METHODS: The bilateral upper first molars were extracted from 4-week-old rats and titanium alloy implants placed only in the left-side extraction sockets. Four weeks after surgery, samples were harvested from the left-side PIST and right-side OMT and total RNA samples isolated. Microarray analysis was used to compare gene expression in PIST and OMT, which was then confirmed using quantitative real-time polymerase chain reaction. Immunohistochemical staining was also performed to confirm protein level expression. RESULTS: The number of genes expressed with more than a twofold change in PIST compared with OMT was 1,102, of which 750 genes were upregulated and 352 genes were downregulated. The messenger RNA (mRNA) expression of three selected genes-Ceacam1, Ifitm1, and MUC4-were more significantly expressed in PIST than in OMT(P < .01). Immunohistochemical localization of CEACAM1, IFITM1, and MUC4 was observed in PIST, but no immunoreaction was recognized in OMT. CONCLUSION: The result of microarray analysis showed that, because of implant placement, 750 genes were upregulated in PIST compared with OMT. CEACAM1, IFITM1, and MUC4 were specifically upregulated in PIST.
Assuntos
Implantes Dentários , Expressão Gênica/genética , Mucosa Bucal/química , Periodonto/química , Animais , Antígenos CD/análise , Antígenos de Diferenciação/análise , Moléculas de Adesão Celular/análise , Ligas Dentárias/química , Endotélio Vascular/química , Perfilação da Expressão Gênica/métodos , Imuno-Histoquímica , Masculino , Análise em Microsséries , Dente Molar/cirurgia , Mucina-4/análise , Proteínas/análise , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Titânio/química , Extração Dentária , Alvéolo Dental/químicaRESUMO
We report two cases of sclerosing epithelioid fibrosarcoma occurring in the deep soft tissue of the thigh, confirmed by molecular analysis and associated with bone metastases in the lumbar vertebrae and the iliac wing at the time of diagnosis. Synchronous bone metastases of sclerosing epithelioid fibrosarcoma are extremely difficult to diagnose because clinical and radiological features are not specific. In addition, the range of differential diagnoses is very wide, including metastatic carcinoma and osteosarcoma. At present, all but three published cases of sclerosing epithelioid fibrosarcoma with bone metastases showed bone metastases during follow-up. We confirm in our two cases that the distinct pattern of immunohistochemical staining for MUC4, associated with the absence of staining for both SATB2, a marker of osteoblastic differentiation, and pan-cytokeratin, allows differentiating between sclerosing epithelioid fibrosarcoma and metastatic carcinoma or osteosarcoma.
Assuntos
Neoplasias Ósseas/secundário , Fibrossarcoma/secundário , Neoplasias de Tecidos Moles/patologia , Adulto , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Proteínas de Ligação à Região de Interação com a Matriz/análise , Proteínas de Ligação à Região de Interação com a Matriz/biossíntese , Mucina-4/análise , Mucina-4/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esclerose/patologia , Coxa da Perna , Fatores de Transcrição/análise , Fatores de Transcrição/biossínteseRESUMO
Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor with a slight male predominance. The tumor has a tendency to arise from deep soft tissue of the trunk and lower extremities. Rare cases are reported to arise from the mediastinal and retroperitoneal areas. Its deceptively bland histologic appearance makes this tumor difficult to diagnose. Also, there are several histologic mimics that may hinder in its diagnosis. We report a case of low-grade fibromyxoid sarcoma from a 48-year-old woman, first documented herein to arise from the sigmoid. We also report the value of CD99, BCL2 and MUC4 stains in the diagnosis of this tumor.
Assuntos
Fibroma/diagnóstico , Neoplasias do Colo Sigmoide/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Antígeno 12E7 , Antígenos CD/análise , Moléculas de Adesão Celular/análise , Colo Sigmoide/patologia , Colo Sigmoide/cirurgia , Feminino , Fibroma/diagnóstico por imagem , Fibroma/cirurgia , Humanos , Pessoa de Meia-Idade , Mucina-4/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Radiografia , Neoplasias do Colo Sigmoide/diagnóstico por imagem , Neoplasias do Colo Sigmoide/cirurgia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/cirurgia , Coloração e RotulagemRESUMO
Sclerosing epithelioid fibrosarcoma is a rare soft tissue tumor that is composed of epithelioid fibroblasts embedded in an abundant extracellular collagenous matrix. They have been shown to be weakly epithelial membrane antigen (EMA) positive by immunohistochemistry and may contain intercellular junctions ultrastructurally. We present a case of a 52-year-old female who presented with a sclerosing Muc-4-positive sarcoma with glandular differentiation of the sciatic nerve, resembling sclerosing epithelioid fibrosarcoma. The glandular component showed strong expression of keratin and EMA and ultrastructurally showed numerous intercellular junctions and intraluminal microvilli, supportive of true glandular differentiation. The patient received preoperative radiotherapy (50 Gray) and subsequent resection of the mass with negative margins. She is currently disease free at 20-month follow-up. This case report describes an unusual sclerosing Muc-4-positive sarcoma with glandular differentiation, distinctive expression of epithelial immunohistochemical markers, and glandular differentiation by electron microscopy.
Assuntos
Mucina-4/biossíntese , Sarcoma/patologia , Nervo Isquiático/patologia , Neoplasias de Tecidos Moles/patologia , Biomarcadores Tumorais/análise , Células Epitelioides/patologia , Feminino , Fibrossarcoma/patologia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mucina-4/análiseRESUMO
The limited effectiveness of therapy for patients with advanced stage head and neck squamous cell carcinoma (HNSCC) or recurrent disease is a reflection of an incomplete understanding of the molecular basis of HNSCC pathogenesis. MUC4, a high molecular weight glycoprotein, is differentially overexpressed in many human cancers and implicated in cancer progression and resistance to several chemotherapies. However, its clinical relevance and the molecular mechanisms through which it mediates HNSCC progression are not well understood. This study revealed a significant upregulation of MUC4 in 78% (68/87) of HNSCC tissues compared with 10% positivity (1/10) in benign samples (P=0.006, odds ratio (95% confidence interval)=10.74 (2.0-57.56). MUC4 knockdown (KD) in SCC1 and SCC10B HNSCC cell lines resulted in significant inhibition of growth in vitro and in vivo, increased senescence as indicated by an increase in the number of flat, enlarged and senescence-associated ß-galactosidase (SA-ß-Gal)-positive cells. Decreased cellular proliferation was associated with G0/G1 cell cycle arrest and decrease expression of cell cycle regulatory proteins like cyclin E, cyclin D1 and decrease in BrdU incorporation. Mechanistic studies revealed upregulation of p16, pRb dephosphorylation and its interaction with histone deacetylase 1/2. This resulted in decreased histone acetylation (H3K9) at cyclin E promoter leading to its downregulation. Orthotopic implantation of MUC4 KD SCC1 cells into the floor of the mouth in nude mice resulted in the formation of significantly smaller tumors (170±18.30 mg) compared to those (375±17.29 mg) formed by control cells (P=0.00007). In conclusion, our findings showed that MUC4 overexpression has a critical role by regulating proliferation and cellular senescence of HNSCC cells. Downregulation of MUC4 may be a promising therapeutic approach for treating HNSCC patients.
Assuntos
Carcinoma de Células Escamosas/patologia , Senescência Celular , Neoplasias de Cabeça e Pescoço/patologia , Mucina-4/fisiologia , Proteínas de Neoplasias/fisiologia , Proteína do Retinoblastoma/fisiologia , Animais , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Montagem e Desmontagem da Cromatina , Ciclina E/análise , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Camundongos , Mucina-4/análise , Invasividade Neoplásica , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: Both MUC1 and MUC4 are high molecular weight glycoproteins and are independent indicators of worse prognosis in many human epithelial cancers including oral squamous cell carcinoma (OSCC). However, there has been no investigation of the clinical importance of the co-expression of MUC1 and MUC4 in OSCC. The aim of this study was to evaluate the co-expression profile of MUC1/MUC4 and analyze the prognostic significance in OSCC. METHODS: We examined the expression profile of MUC1 and MUC4 in OSCC tissues from 206 patients using immunohistochemistry. The co-expression profile of MUC1/MUC4 and its prognostic significance in OSCC was statistically analyzed. RESULTS: MUC1 and MUC4 overexpression were strongly correlated with each other (p < 0.0001) and a combination of both MUC1 and MUC4 expression was a powerful indicator for tumor aggressiveness such as tumor size (p = 0.014), lymph node metastasis (0.0001), tumor stage (p = 0.006), diffuse invasion (p = 0.028), and vascular invasion (p = 0.014). The MUC1/MUC4 double-positive patients showed the poorest overall and disease-free survival. Multivariate analysis revealed that MUC1/MUC4 double-positivity was the strong independent prognostic factor for overall and disease-free survival (p = 0.007 and (p = 0.0019), in addition to regional recurrence (p = 0.0025). CONCLUSIONS: Taken together, these observations indicate that the use of a combination of MUC1/MUC4 can predict outcomes for patients with OSCC. This combination is also a useful marker for predicting regional recurrence. MUC1 and MUC4 may be attractive targets for the selection of treatment methods in OSCC.
Assuntos
Carcinoma de Células Escamosas/química , Neoplasias Bucais/química , Mucina-1/análise , Mucina-4/análise , Recidiva Local de Neoplasia/química , Idoso , Vasos Sanguíneos/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Mucina-1/metabolismo , Mucina-4/metabolismo , Invasividade Neoplásica , Estadiamento de Neoplasias , Curva ROC , Taxa de Sobrevida , Carga TumoralRESUMO
We report the first 2 genetically confirmed cases of primary renal sclerosing epithelioid fibrosarcoma (SEF), occurring in a 17-year-old boy and a 61-year-old woman. In both cases, the tumors demonstrated the typical epithelioid clear cell morphology associated with extensive hyalinizing fibrosis, raising the differential diagnosis of solitary fibrous tumor, metanephric stromal tumor, and the sclerosing variant of clear cell sarcoma of the kidney. Both neoplasms demonstrated diffuse immunoreactivity for MUC4, a highly specific marker for SEF, and both demonstrated evidence of rearrangement of both the EWSR1 and CREB3L1 genes, which have recently been shown to be fused in this entity. Both neoplasms presented with metastatic disease. Primary renal SEF represents yet another translocation-associated sarcoma now shown to arise primarily in the kidney.
Assuntos
Biomarcadores Tumorais/genética , Proteínas de Ligação a Calmodulina/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Células Epitelioides/patologia , Fibrossarcoma/genética , Fusão Gênica , Neoplasias Renais/genética , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA/genética , Adolescente , Biomarcadores Tumorais/análise , Células Epitelioides/química , Evolução Fatal , Feminino , Fibrossarcoma/química , Fibrossarcoma/secundário , Fibrossarcoma/terapia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Renais/química , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Mucina-4/análise , Proteína EWS de Ligação a RNA , Esclerose , Tomografia Computadorizada por Raios XRESUMO
AIM: To determine the expression of membrane-bound mucins and glycan side chain sialic acids in Helicobacter pylori (H. pylori)-associated, non-steroidal inflammatory drug (NSAID)-associated and idiopathic-gastric ulcers. METHODS: We studied a cohort of randomly selected patients with H. pylori (group 1, n = 30), NSAID (group 2, n = 18), combined H. pylori and NSAID associated gastric ulcers (group 3, n = 24), and patients with idiopathic gastric ulcers (group 4, n = 20). Immunohistochemistry for MUC1, MUC4, MUC17, and staining for Erythrina cristagalli agglutinin and Sambucus nigra agglutinin (SNA) lectins was performed on sections from the ulcer margins. RESULTS: Staining intensity of MUC17 was higher in H. pylori ulcers (group 1) than in idiopathic ulcers (group 4), 11.05 ± 3.67 vs 6.93 ± 4.00 for foveola cells, and 10.29 ± 4.67 vs 8.00 ± 3.48 for gland cells, respectively (P < 0.0001). In contrast, MUC1 expression was higher in group 4 compared group 1, 9.89 ± 4.17 vs 2.93 ± 5.13 in foveola cells and 7.63 ± 4.60 vs 2.57± 4.50 for glands, respectively (P < 0.0001). SNA lectin staining was increased in group 4, in parallel to elevated MUC1 expression, indicating more abundant α2-6 sialylation in that group. CONCLUSION: Cytoplasmic MUC17 staining was significantly decreased in the cases with idiopathic ulcer. The opposite was observed for both MUC1 and SNA lectin. This observation may reflect important pathogenic mechanisms, since different mucins with altered sialylation patterns may differ in their protection efficiency against acid and pepsin.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Membrana Celular/química , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Mucinas/análise , Polissacarídeos/análise , Úlcera Gástrica/metabolismo , Estômago/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Membrana Celular/efeitos dos fármacos , Membrana Celular/microbiologia , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucina-1/análise , Mucina-4/análise , Ácido N-Acetilneuramínico/análise , Lectinas de Plantas , Valor Preditivo dos Testes , Estudos Retrospectivos , Proteínas Inativadoras de Ribossomos , Estômago/efeitos dos fármacos , Estômago/microbiologia , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/microbiologia , Adulto JovemRESUMO
Antibodies are a class of molecules widely used in bioengineering and nanomedicine for applications involving protein recognition and targeting. Here we report an efficient method for universal conjugation of antibodies to lipid-coated nanoparticles using radially oriented FcγRIs. This method is performed in physiological solution with no additional coupling reagents, thereby avoiding problems with antibody stability and functionality. Coupling to the Fc region of the antibody avoids aggregation and polymerization allowing high yield. In addition, the antibody is oriented perpendicular to the surface so that the binding sites are fully functional. Using this method we demonstrate quantitative profiling of a panel of four membrane-bound cancer biomarkers (claudin-4, mesothelin, mucin-4, and cadherin-11) on four cell lines (Panc-1, MIA PaCa-2, Capan-1, and HPDE). We show that by designing the lipid coating to minimize aggregation and nonspecific binding, we can obtain absolute values of biomarker expression levels as number per unit area on the cell surface. This method is applicable to a wide range of technologies, including solution based protein detection assays and active targeting of cell surface membrane biomarkers.
Assuntos
Imunoconjugados/química , Nanopartículas/química , Neoplasias Pancreáticas/diagnóstico , Receptores de IgG/química , Animais , Biomarcadores Tumorais/análise , Caderinas/análise , Linhagem Celular Tumoral , Claudina-4/análise , Proteínas Ligadas por GPI/análise , Humanos , Mesotelina , Camundongos , Mucina-4/análise , Proteínas Recombinantes/químicaRESUMO
BACKGROUND/AIM: Mucin 4 (MUC4) is a cell surface glycoprotein that is overexpressed in most pancreatic tumors. The aim of the present study was to characterize MUC4 expression in experimental pancreatic cancer in order to clarify the correlation between MUC4 and pancreatic cancer histology in vivo. MATERIALS AND METHODS: Pancreatic xenograft tumors were generated in immunodeficient mice (n=15) by subcutaneous injection of MUC4(+) human pancreatic cancer cell lines Capan-1, HPAF-II or CD18/HPAF. MUC4 immunoreactivity was compared between the cancer models. Alpha-smooth muscle actin (α-SMA) was used to identify cancer-associated fibroblasts and the amount of collagen fibers was quantified with sirius red. RESULTS: Tumor incidence was 100%. Tumor size showed no difference across groups (p=0.796). The median MUC4 count was highest in Capan-1 tumors (p=0.002). α-SMA and collagen extent were also highest in Capan-1 tumors (p=0.018). CONCLUSION: The Capan-1 xenograft model could serve as a valuable resource to test new therapeutic strategies targeting MUC4 in pancreatic cancer.