RESUMEN
Objective: To investigate the clinicopathological features, diagnostic criteria and differential diagnosis of primary salivary gland-type duct carcinoma of lung(LSDC). Methods: Two patients with LSDC after surgical resection in Shanghai Pulmonary Hospital from 2020 to 2021 were included; their clinical parameters as well as pathological, immunohistochemical and molecular characteristics of the tumors were analyzed. The relevant literature was also reviewed. Results: Both patients were male, aged 49(case 1) and 64(case 2) years, respectively, and with a history of smoking. The chest computed tomography scan showed both lesions to be centrally located. Gross examination showed the maximum diameters were 16 mm and 35 mm, respectively. The histomorphology of LSDC resembled ductal carcinoma of breast, with intraductal islands of neoplastic cells, which also formed solid nests, papillary, micropapillary and cribriform structures. There was frequent accompanying comedo-like necrosis. The neoplasm cells were markedly heteromorphic, possessing large irregular nuclei with prominent nucleoli, abundant eosinophilic or clear cytoplasm, and mitotic figures were common. Both cases of LSDC were immunoreactive for CKpan, CK7, AR, HER2 staining was (2+) and were negative for TTF1, Napsin A, p40, GATA3, mammaglobin, GCDFP15, SOX10, PSA, P504S, ER, PR, vimentin, S-100, SMA, CK5/6 and p63. The tumor showed double-layer cell structure of the duct, and some basal cells/myoepithelial cells expressed p40 and CK5/6. Case 1 had no gene mutation while case 2 harbored TP53 and KMT2A gene mutation detected by next generation sequencing. Conclusions: LSDC is a very rare and highly aggressive salivary-type malignant tumor. The postoperative diagnosis mainly depends on histopathology and immunohistochemistry, attention should be paid to differential diagnosis to prevent missed diagnosis.
Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Biomarcadores de Tumor/análisis , Preescolar , China , Humanos , Pulmón , Masculino , Conductos Salivales/químicaRESUMEN
Objective: To investigate the clinicopathological features, diagnostic criteria and differential diagnosis of primary salivary gland-type duct carcinoma of lung(LSDC). Methods: Two patients with LSDC after surgical resection in Shanghai Pulmonary Hospital from 2020 to 2021 were included; their clinical parameters as well as pathological, immunohistochemical and molecular characteristics of the tumors were analyzed. The relevant literature was also reviewed. Results: Both patients were male, aged 49(case 1) and 64(case 2) years, respectively, and with a history of smoking. The chest computed tomography scan showed both lesions to be centrally located. Gross examination showed the maximum diameters were 16 mm and 35 mm, respectively. The histomorphology of LSDC resembled ductal carcinoma of breast, with intraductal islands of neoplastic cells, which also formed solid nests, papillary, micropapillary and cribriform structures. There was frequent accompanying comedo-like necrosis. The neoplasm cells were markedly heteromorphic, possessing large irregular nuclei with prominent nucleoli, abundant eosinophilic or clear cytoplasm, and mitotic figures were common. Both cases of LSDC were immunoreactive for CKpan, CK7, AR, HER2 staining was (2+) and were negative for TTF1, Napsin A, p40, GATA3, mammaglobin, GCDFP15, SOX10, PSA, P504S, ER, PR, vimentin, S-100, SMA, CK5/6 and p63. The tumor showed double-layer cell structure of the duct, and some basal cells/myoepithelial cells expressed p40 and CK5/6. Case 1 had no gene mutation while case 2 harbored TP53 and KMT2A gene mutation detected by next generation sequencing. Conclusions: LSDC is a very rare and highly aggressive salivary-type malignant tumor. The postoperative diagnosis mainly depends on histopathology and immunohistochemistry, attention should be paid to differential diagnosis to prevent missed diagnosis.
Asunto(s)
Preescolar , Humanos , Masculino , Biomarcadores de Tumor/análisis , Neoplasias de la Mama , Carcinoma Ductal de Mama , China , Pulmón , Conductos Salivales/químicaAsunto(s)
Hibridación in Situ/métodos , Proteínas de Neoplasias/análisis , ARN Mensajero/análisis , ARN Neoplásico/análisis , Receptores Androgénicos/análisis , Conductos Salivales/química , Neoplasias de las Glándulas Salivales/química , Manejo de Especímenes/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Formaldehído , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Adhesión en Parafina , Isoformas de Proteínas/análisis , Isoformas de Proteínas/genética , Receptores Androgénicos/genética , Fijación del TejidoRESUMEN
Salivary duct carcinoma (SDC) is an aggressive carcinoma with poor prognosis. Although anti-HER2 therapy is a potential treatment option for HER2-positive SDC, other potential therapeutic targets are not known, in particular for HER2-negative cases. In this study, the recently identified receptors tyrosine kinases MET and tropomyosin-receptor kinase (Trk) were investigated as potential therapeutic targets. A total of 28 consecutive, surgically resected, de novo SDC cases were selected after evaluating histology and immunohistochemical expression of androgen receptor. Immunohistochemical expression of c-erb2, TrkA, TrkB, TrkC, and c-MET was analyzed, and the genetic status of the HER2 and MET genes was investigated through dual-color silver in situ hybridization. High expression of c-MET or Trk was defined as that above the median value. Among the 28 SDC cases, 64.3% (18/28) were HER2-positive. c-MET expression varied, with a median H-score of 65 (range, 0 to 200). Copy number gain and amplification of MET were noted in 57.1% (16/28) and 10.7% (3/28) of cases, respectively. TrkA was variably expressed, with a median H-score of 100 (range, 0 to250). High TrkA expression was significantly related to an inferior overall survival rate in HER2-negative SDC. High expression of TrkA and c-MET and MET copy number gain/amplification were frequent events in SDC, and high expression of TrkA revealed the tendency to be related to poor prognosis in HER2-negative SDC. TrkA and MET may be possible therapeutic targets in SDC, especially in HER2-negative SDC.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma/química , Proteínas Proto-Oncogénicas c-met/análisis , Receptor trkA/análisis , Conductos Salivales/química , Neoplasias de las Glándulas Salivales/química , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma/genética , Carcinoma/mortalidad , Carcinoma/patología , Femenino , Amplificación de Genes , Dosificación de Gen , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas c-met/genética , Receptor ErbB-2/análisis , Factores de Riesgo , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/mortalidad , Neoplasias de las Glándulas Salivales/patología , Factores de Tiempo , Regulación hacia ArribaRESUMEN
Primary salivary gland-type lung cancer is a heterogeneous group of neoplasms arising from the seromucinous glands of the respiratory tract. Histopathologically, they are identical to salivary gland neoplasms of the head and neck. While mucoepidermoid carcinoma and adenoid cystic carcinoma are overwhelmingly the most common subtypes found in the lung, reports of uncommon subtypes can be found in the literature. We report a case of a 73-year-old woman with primary lung salivary duct carcinoma, mucin-rich variant--an exceedingly rare subtype of an already rare malignant salivary-type neoplasm. One case of primary lung salivary duct carcinoma has been reported in the literature; however, the mucin-rich variant has never been described in the lung. Furthermore, the tumor in our case bears a rare BRAF G464V mutation. To our knowledge, this is the first reported case of a BRAF G464V mutation detected in a salivary duct carcinoma or any other salivary-type neoplasm.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Mucinas/análisis , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/patología , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/química , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Análisis Mutacional de ADN , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/química , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Escisión del Ganglio Linfático , Imagen Multimodal/métodos , Mutación , Neumonectomía , Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas B-raf/genética , Conductos Salivales/química , Conductos Salivales/cirugía , Neoplasias de las Glándulas Salivales/química , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/cirugía , Toracotomía , Tomografía Computarizada por Rayos XRESUMEN
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-dependent protein kinase (PKA)-regulated Cl(-) channel, crucial for epithelial cell regulation of salt and water transport. Previous studies showed that ezrin, an actin binding and A-kinase anchoring protein (AKAP), facilitates association of PKA with CFTR. We used immunohistochemistry and immunogold transmission electron microscopy to localize CFTR, ezrin, and PKA type II regulatory (RII) and catalytic (C) subunits in striated duct cells of human parotid and submandibular glands. Immunohistochemistry localized the four proteins mainly to the apical membrane and the apical cytoplasm of striated duct cells. In acinar cells, ezrin localized to the luminal membrane, and PKA RII subunits were present in secretory granules, as previously described. Immunogold labeling showed that CFTR and PKA RII and C subunits were localized to the luminal membrane and associated with apical granules and vesicles of striated duct cells. Ezrin was present along the luminal membrane, on microvilli and along the junctional complexes between cells. Double labeling showed specific protein associations with apical granules and vesicles and along the luminal membrane. Ezrin, CFTR, and PKA RII and C subunits are co-localized in striated duct cells, suggesting the presence of signaling complexes that serve to regulate CFTR activity.
Asunto(s)
Proteínas Quinasas Dependientes de AMP Cíclico/análisis , Regulador de Conductancia de Transmembrana de Fibrosis Quística/análisis , Proteínas del Citoesqueleto/análisis , Glándula Parótida/química , Conductos Salivales/química , Glándula Submandibular/química , Proteínas de Anclaje a la Quinasa A/análisis , Membrana Celular/química , Membrana Celular/ultraestructura , Subunidades Catalíticas de Proteína Quinasa Dependientes de AMP Cíclico/análisis , Proteína Quinasa Tipo II Dependiente de AMP Cíclico/análisis , Citoplasma/química , Citoplasma/ultraestructura , Humanos , Inmunohistoquímica , Uniones Intercelulares/química , Uniones Intercelulares/ultraestructura , Microscopía Electrónica de Transmisión , Microvellosidades/química , Microvellosidades/ultraestructura , Glándula Parótida/citología , Conductos Salivales/citología , Vesículas Secretoras/química , Vesículas Secretoras/ultraestructura , Glándula Submandibular/citología , Vacuolas/química , Vacuolas/ultraestructuraRESUMEN
ß-defensins are small, cationic peptides with broad-spectrum antimicrobial activity that are produced by mucosal epithelia. However, little is known about the expression of ß-defensins in the major salivary glands. The purpose of this study was to characterize expression of rat ß-defensin-1 (RBD-1) and -2 (RBD-2) mRNA within the major salivary glands together with the effect of injection of intraductal lipopolysaccharide (LPS) on that expression. ß-defensin mRNA expression was quantitated by RT-PCR in salivary gland tissues and salivary acinar and striated duct cells collected by laser captured microdissection. RBD-1 and -2 were expressed in the parotid gland, the submandibular gland, and the sublingual gland. ß-defensins were expressed in both the acinar and striated duct cells of the major salivary glands. Intraductal injection of LPS increased expression of RBD-1 and -2 mRNA, which peaked at 12 hrs. These results suggest that salivary cells (acinar and striated duct cells) have the potential to produce ß-defensins.
Asunto(s)
Lipopolisacáridos/farmacología , ARN Mensajero/análisis , Glándulas Salivales/química , beta-Defensinas/análisis , Animales , Defensinas/análisis , Defensinas/efectos de los fármacos , Escherichia coli , Hibridación in Situ , Terapia por Láser/métodos , Masculino , Microdisección/métodos , Glándula Parótida/química , Glándula Parótida/efectos de los fármacos , Isoformas de Proteínas/análisis , Isoformas de Proteínas/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Conductos Salivales/química , Conductos Salivales/efectos de los fármacos , Glándulas Salivales/efectos de los fármacos , Glándula Sublingual/química , Glándula Sublingual/efectos de los fármacos , Glándula Submandibular/química , Glándula Submandibular/efectos de los fármacos , Factores de Tiempo , beta-Defensinas/efectos de los fármacosRESUMEN
Nuclear receptors and transcription factors regulate the functions of many genes involved in cellular physiology and pathology (e.g. tumorigenesis and autoimmune diseases). The present study was performed to define the expression and the regulation of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), and nuclear factor E2-related factor 2 (Nrf2) in the rat parotid gland. Constitutive expression, as well as expression after stimulation with specific inducers for AhR [2,3,7,8-tetrachloro-dibenzylo-p-dioxin (TCDD)], Nrf2(oltipraz), PXR (dexamethasone), and CAR (phenobarbital), was evaluated using the quantitative PCR. Cellular localization of the nuclear receptors and the transcription factor was visualized by immunohistochemical staining. The study revealed constitutive expression of AhR as well as Nrf2, and their induction by TCDD andoltipraz, respectively. Immunohistochemical analysis revealed constitutive, predominantly cytoplasmic, expression of the AhR receptor, especially in interlobular striated duct cells, with nuclear shift upon exposure to TCDD. Inducible expression of Nfr2 was found mainly in the cytoplasm of intralobular striated duct cells. Constitutive expression of PXR and CAR was not found. Bearing in mind the involvement of AhR and Nrf2 in the regulation of many genes, it seems that these factors may play also a role in salivary gland physiology and pathology.
Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/análisis , Factor 2 Relacionado con NF-E2/análisis , Glándula Parótida/química , Receptores de Hidrocarburo de Aril/análisis , Receptores Citoplasmáticos y Nucleares/análisis , Receptores de Esteroides/análisis , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/efectos de los fármacos , Núcleo Celular/química , Núcleo Celular/ultraestructura , Receptor de Androstano Constitutivo , Citoplasma/química , Citoplasma/ultraestructura , Dexametasona/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Glándula Parótida/citología , Glándula Parótida/efectos de los fármacos , Fenobarbital/farmacología , Dibenzodioxinas Policloradas/farmacología , Receptor X de Pregnano , Pirazinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Hidrocarburo de Aril/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Receptores de Esteroides/efectos de los fármacos , Conductos Salivales/química , Conductos Salivales/citología , Tionas , TiofenosRESUMEN
OBJECTIVE: The objective of this study was to investigate the potential role of Toll-like receptor 9-dependent p38 MAPK signaling pathway in the pathogenesis of primary Sjögren's syndrome (pSS) in NOD/Ltj mouse, aiming to identify an ideal target therapy model for human pSS. METHODS: NOD/Ltj mice were chosen as a model of pSS. The Toll-like receptor 9 and p-p38 MAPK double-positive peripheral blood mononuclear cells (PBMCs) of 4-, 5-, 8-, 10-, and 15-week-old NOD/Ltj mouse were analyzed by flow cytometry. The expressions of Toll-like receptor 9 and p-p38 MAPK in the submandibular gland (SMG) were also examined by immunohistochemistry. The change of stimulated salivary flow rate was dynamically measured, and the histopathology of SMG was evaluated by hematoxylin and eosin stain. RESULTS: The stimulated salivary flow rate in NOD/Ltj was reduced to 50-60% of the flow rate of control mice since the fifth week onwards. The Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs in both groups increased gradually from 5 weeks, peaked at 8 weeks and then gradually decreased at 10 weeks, yet the percentage of Toll-like receptor 9 and p-p38MAPK double-positive PBMCs in 5-, 8-, and 10-week-old NOD/Ltj mouse was significantly increased compared with those in control subjects. After the 10th week onwards, there were no significant differences in the Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs between NOD/Ltj mice and controls. Immunohistochemical staining showed that Toll-like receptor 9 was positive in the acinar epithelium cells and infiltrating lymphocytes in NOD/Ltj mice. p-p38 MAPK was detected in infiltrating lymphocytes and few ductal or acinar epithelium cells adjacent to infiltrating lymphocytes in NOD/Ltj mice. CONCLUSIONS: From the fifth week till the tenth week, Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs were significantly increased in NOD/Ltj mice, accompanied with reduced stimulated salivary flow rate and Toll-like receptor 9 or p-p38 MAPK positive infiltrating lymphocytes observed in the SMG of NOD/Ltj mouse. Our results indicated that activation of Toll-like receptor 9-depended p38 MAPK signal pathway in PBMCs was an early event in pSS which made NOD/Ltj as an ideal therapy model to test the treatment effects of p38 MAPK or Toll-like receptor 9 inhibitors on pSS.
Asunto(s)
Sistema de Señalización de MAP Quinasas/fisiología , Síndrome de Sjögren/etiología , Receptor Toll-Like 9/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/fisiología , Animales , Modelos Animales de Enfermedad , Epitelio/química , Epitelio/patología , Femenino , Leucocitos Mononucleares/enzimología , Leucocitos Mononucleares/patología , Linfocitos/química , Linfocitos/enzimología , Linfocitos/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Saliva/metabolismo , Conductos Salivales/química , Conductos Salivales/enzimología , Conductos Salivales/patología , Tasa de Secreción/fisiología , Síndrome de Sjögren/patología , Glándula Submandibular/química , Glándula Submandibular/enzimología , Glándula Submandibular/patología , Receptor Toll-Like 9/análisis , Proteínas Quinasas p38 Activadas por Mitógenos/análisisRESUMEN
OBJECTIVE: To determine and compare the presence and in situ localization of the glycosphingolipid ganglioside GM1 in human salivary glands using the biomarkers for GM1: cholera toxin and antibodies against GM1. MATERIALS AND METHODS: Immunohistochemical analyses were performed on sections of adult human submandibular, parotid and palatinal glands using cholera toxin sub-unit B and two polyclonal antibodies against ganglioside GM1 as biomarkers. RESULTS: Immunofluorescence microscopy showed that the toxin and antibodies were co-localized in some acini but not in others. The cholera toxin mainly reacted with the cell membranes of the mucous acini in the submandibular gland, while incubation with the antibody against GM1 gave rise to a staining of the cytoplasm. The cytoplasm in some secretory acinar cells in the parotid gland was stained by the cholera toxin, whereas only small spots on the plasma membranes reacted with anti-GM1. The plasma membranes in the parotid excretory ducts appeared to react to anti-GM1, but not to cholera toxin. CONCLUSIONS: Cholera toxin induces the expression of ion channels and carriers in the small intestine and increases the production of secretory mucins. Although their mutual immunohistochemical localization may differ, both cholera toxin and ganglioside GM1 are present in the mucin-producing acini from salivary glands. This could point to a relationship between ganglioside expression and production of salivary mucins.
Asunto(s)
Toxina del Cólera , Gangliósido G(M1)/análisis , Glándulas Salivales/química , Adulto , Anticuerpos , Biomarcadores , Cadáver , Membrana Celular/química , Membrana Celular/ultraestructura , Citoplasma/química , Citoplasma/ultraestructura , Humanos , Inmunohistoquímica , Microscopía Fluorescente , Mucinas/química , Glándula Parótida/química , Glándula Parótida/citología , Conductos Salivales/química , Conductos Salivales/citología , Glándulas Salivales/citología , Glándulas Salivales Menores/química , Glándulas Salivales Menores/citología , Membrana Serosa/química , Membrana Serosa/citología , Glándula Submandibular/química , Glándula Submandibular/citologíaRESUMEN
PURPOSE: The aim of this study was to investigate expression of CD147 and MMP-9 in salivary duct carcinoma (SDC) so as to determine whether these two genes may be correlated with poor prognosis of SDC. METHODS: We examined the significance of the CD147 and MMP-9 expression in SDC (n = 35), non-cancerous salivary tissue (n = 20) in previously untreated patients using immunohistochemical staining. Furthermore, we analyzed the correlation between the expression of these two genes and various clinicopathologic factors including survival status of patients with SDC. RESULTS: Positive stain of CD147 and MMP-9 was seen in all 35 cases of tumor samples. A statistical correlation was observed between CD147 and MMP-9 expression in SDC tissues. The incidences of high expression were 45.71% for CD147 and 51.43% for MMP-9 in 35 SDC tissues, respectively. High expression of CD147 and MMP-9 was significantly correlated with clinical feature and shorter progression-free survival (PFS) (P (CD147) = 0.031; P (MMP-9) = 0.020) and overall survival (OS) (P (CD147) = 0.044; P (MMP-9) = 0.013). CONCLUSION: CD147 and MMP-9 expression is correlated with invasion, metastasis and shorter PFS/OS of SDC. Patients with high expression of CD147 and MMP-9 had poor prognosis than SDC patients with low expression.
Asunto(s)
Basigina/biosíntesis , Carcinoma Ductal/patología , Metaloproteinasa 9 de la Matriz/biosíntesis , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/patología , Adulto , Anciano , Carcinoma Ductal/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica/estadística & datos numéricos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Conductos Salivales/química , Neoplasias de las Glándulas Salivales/metabolismoRESUMEN
BACKGROUND/AIMS: There are still uncertainties regarding the use of whole and parotid ductal saliva as indicators of chronic exposure to fluoride. This study evaluated the effect of water fluoride concentration, age, gender, geographical area and localization (urban/rural) on fluoride concentrations in whole and ductal saliva. METHODS: Subjects (n = 300) aged 3-7, 14-20, 30-40 and 50-60 years, from five communities (A-E) with different fluoride concentrations in the drinking water, participated in the study. Two samples of drinking water and parotid and whole saliva were collected for each subject and were analyzed for fluoride using appropriate electrode techniques. RESULTS: Mean water F concentrations (±SE, mg/l, n = 60) were 0.09 ± 0.01, 0.15 ± 0.01, 0.66 ± 0.01, 0.72 ± 0.02, and 1.68 ± 0.08 for A-E, respectively. Mean F concentrations (±SE, mg/l, n = 15) ranged between 0.014 ± 0.002 (A, 3-7 years) and 0.297 ± 0.057 (D, 14-20 years) for whole saliva and 0.009 ± 0.001 (C, 30-40 years) and 0.284 ± 0.038 (E, 50-60 years) for parotid saliva. Results of multivariate linear regression analysis showed that geographical area and water fluoride concentration exerted the strongest influence in whole and ductal saliva F concentrations, respectively. CONCLUSION: Therefore, parotid ductal saliva seems to be a more appropriate biomarker of fluoride exposure, and factors like age and localization should also be considered when using this biomarker.
Asunto(s)
Agua Potable/química , Fluoruros/análisis , Glándula Parótida/química , Saliva/química , Conductos Salivales/química , Adolescente , Adulto , Análisis de Varianza , Biomarcadores , Niño , Preescolar , Exposición a Riesgos Ambientales , Femenino , Humanos , Electrodos de Iones Selectos , Modelos Lineales , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Adulto JovenRESUMEN
In submandibular gland atrophy, most acinar cells disappear by apoptosis, while many duct cells remain. The present study aimed to establish whether Bcl-2 and Bax, members of the Bcl-2 gene family, regulating the signalling pathway of apoptosis were involved in duct cell survival and acinar cell death in atrophic submandibular glands. The excretory duct of rat submandibular gland was doubly ligated with metal clips from 1 to 14 days to induce atrophy to the gland. The expressions of Bcl-2 and Bax in the atrophic submandibular gland were examined using immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Immunohistochemically, Bcl-2 expression was identified in duct cells in the experimental glands at all time points. Some acinar cells showed Bax positivity 1 day after excretory duct ligation, and there were more Bax-positive acinar cells on days 3 and 5 when many apoptotic acinar cells were observed. Analysis by RT-PCR showed that the expression of mRNA for Bcl-2 became stronger as the glandular atrophy progressed and that Bax mRNA strongly expressed on days 1 and 3. These observations suggest that Bcl-2 inhibits duct cell apoptosis and Bax promotes apoptosis of acinar cells during atrophy of submandibular glands.
Asunto(s)
Genes bcl-2 , Conductos Salivales/metabolismo , Transducción de Señal/genética , Glándula Submandibular/metabolismo , Glándula Submandibular/patología , Proteína X Asociada a bcl-2/genética , Animales , Apoptosis/genética , Atrofia/genética , Expresión Génica , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Ligadura , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Conductos Salivales/química , Conductos Salivales/patología , Glándula Submandibular/química , Proteína X Asociada a bcl-2/análisisAsunto(s)
Carcinoma Ductal/diagnóstico , Inmunohistoquímica/métodos , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/diagnóstico , Anciano , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/secundario , Carcinoma Ductal/química , Carcinoma Ductal/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/secundario , Conductos Salivales/química , Neoplasias de las Glándulas Salivales/química , Neoplasias de las Glándulas Salivales/cirugía , Resultado del TratamientoRESUMEN
The presence of invasive micropapillary component has been reported to be associated with salivary duct carcinoma and poor outcomes. Herein is described a rare case of invasive micropapillary salivary duct carcinoma of the parotid gland in a 60-year-old man. The micropapillary component was approximately 70% of the area of the tumor. Squamous differentiation was focally seen adjacent to the micropapillary component. On immunohistochemistry the ordinary salivary duct carcinoma component was positive for gross cystic disease fluid protein-15 (GCDFP-15), androgen receptor (AR), and HER2/neu, whereas both micropapillary and squamous components were negative for GCDFP-15 and AR. Immunohistochemical staining for D2-40 highlighted the lymph vessel invasion of tumor cells. This patient developed metastases in the lymph nodes of the neck, and also in the liver, lung, and brain. The lymph nodes and liver metastases had both ordinary salivary duct carcinoma and micropapillary components. The patient died of tumor 11 months after the initial surgical operation. The results support that the presence of micropapillary component is associated with more aggressive behavior of salivary duct carcinoma. It is also important for pathologists to recognize that GCDFP-15 and AR expression can be reduced in micropapillary carcinoma in the differential diagnosis of metastatic tumor.
Asunto(s)
Carcinoma Ductal/patología , Neoplasias de la Parótida/patología , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/patología , Biomarcadores de Tumor/análisis , Carcinoma Ductal/química , Carcinoma Ductal/terapia , Proteínas Portadoras/análisis , Quimioterapia Adyuvante , Terapia Combinada , Resultado Fatal , Técnica del Anticuerpo Fluorescente Directa , Glicoproteínas/análisis , Humanos , Masculino , Proteínas de Transporte de Membrana , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Neoplasias de la Parótida/química , Receptor ErbB-2/análisis , Receptores Androgénicos/análisis , Conductos Salivales/química , Neoplasias de las Glándulas Salivales/químicaRESUMEN
Rat submandibular glands can recover their function and secretory protein content following ductal ligation-induced atrophy. Morphological studies have established that following ligation, deligation of the gland allows the regeneration of new salivary gland tissue. However, little is known about changes happening during early regeneration following intra-oral duct ligation, which does not damage the parasympathetic nerves. Glands that had been 2 weeks ligated or 2 weeks ligated + 3 days deligated were compared. Tissue was prepared for histological, immunohistochemical (SMG-B and Ki-67) and immunocytochemical analyses (smooth muscle actin, aquaporin 5). Haematoxylin and eosin staining of deligated glands showed that some acini regained their cytoplasmic volume; moreover, the loss of Alcian blue/periodic acid-Schiff's staining from the lumen of ducts suggested successful deligation. The deligated gland was characterized by atypical acinar-ductal branched structures, which were less frequent in the ligated gland and rarely seen in normal unoperated tissue. Myoepithelial cells were also investigated since changes in their morphology reflected changes in the acini morphology not readily detected by conventional staining. Actin staining revealed the presence of some shrunken acini in the atrophic tissue, whereas they had regained their normal morphology in the deligated gland suggesting that the acini were recovering. Some acini during deligation regained aquaporin 5 expression, which had decreased during atrophy. SMG-B protein, located in the pro-acinar cell during gland development and usually found in the intercalated duct cells in the adult, was detected in the newly formed acini of the deligated gland. This study suggests that morphological markers of regeneration appear as early as 3 days following ligation removal.
Asunto(s)
Regeneración/fisiología , Glándula Submandibular/química , Glándula Submandibular/fisiología , Actinas/análisis , Animales , Acuaporina 5/análisis , Biomarcadores/análisis , Técnica del Anticuerpo Fluorescente , Antígeno Ki-67/análisis , Ligadura , Ratas , Ratas Wistar , Conductos Salivales/química , Conductos Salivales/citología , Conductos Salivales/cirugía , Proteínas y Péptidos Salivales/análisis , Glándula Submandibular/citología , Glándula Submandibular/cirugía , Factores de TiempoRESUMEN
Salivary duct carcinoma (SDC), a rare malignancy, manifests remarkable morphologic and biologic resemblance to high-grade mammary ductal carcinoma. We contend that, similar to mammary ductal carcinoma, hormones and growth factors may play a role in SDCs. Our aim was to determine the incidence and clinical significance of the expression of several hormone and growth factor receptors and evaluate their potential in therapeutic stratification of SDC patients in the largest cohort studied to date. Eighty-four archived tumor tissue blocks were analyzed immunohistochemically for expression of estrogen receptor-beta (ERbeta), androgen receptor (AR), and proline, glutamic acid, and leucine-rich protein-1 and growth factor receptors HER-2 and epidermal growth factor receptor. The results were correlated with available pathologic, demographic, and clinical data from 59 of 84 cases. Proline, glutamic acid, and leucine-rich protein-1, ERbeta, and AR were expressed individually in 94% (71/76), 73% (57/80), and 67% (56/84) of SDCs, respectively, and coexpressed in 45% (34/75). AR was expressed significantly more often in SDCs of men than in SDCs of women [79% (35/57) vs. 33% (9/27), P<0.001]. Epidermal growth factor receptor and HER-2 were overexpressed individually in 48% (40/83) and 25% (21/84), respectively, and co-overexpressed in 12% (10/83). Survival decreased significantly in patients with lymph node metastasis (P=0.002) and positive surgical margins (P=0.006). Lack of ERbeta expression correlated with increased local and regional recurrence (P=0.05 and P=0.002, respectively). Together, these results indicate that (a) ERbeta down-regulation is associated with adverse clinical features, (b) lymph node and surgical margin status are significant survival factors, and (c) the differential expression of these hormones and growth factor receptors may assist in triaging patients with SDC for novel therapies.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma/química , Selección de Paciente , Conductos Salivales/química , Neoplasias de las Glándulas Salivales/química , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/terapia , Proteínas Co-Represoras , Estudios de Cohortes , Regulación hacia Abajo , Receptores ErbB/análisis , Receptor beta de Estrógeno/análisis , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Pronóstico , Receptor ErbB-2/análisis , Receptores Androgénicos/análisis , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/mortalidad , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/terapia , Transactivadores/análisis , Factores de TranscripciónAsunto(s)
Adenocarcinoma/patología , Conductos Salivales/patología , Neoplasias de las Glándulas Salivales/patología , Adenocarcinoma/química , Adenocarcinoma/genética , Biomarcadores de Tumor/análisis , Genotipo , Humanos , Fenotipo , Conductos Salivales/química , Neoplasias de las Glándulas Salivales/química , Neoplasias de las Glándulas Salivales/genéticaRESUMEN
Transduction of salivary glands with antimicrobial peptide genes has great potential for oral infection control. Our ultimate goal is to introduce antimicrobial peptide genes into salivary glands that secrete these peptides into saliva to control bacterial/fungal infection in the oral cavity. However, an animal study model to test this potential has not been established. Therefore, we determined to test (i) whether the potent antimicrobial peptide human beta-defensin-2 (hBD-2) can be overexpressed in saliva after transduction of salivary glands and (ii) whether oral fungal infection can be developed in a NOD/SCID murine model. Lentiviral vector SIN18cPPTRhMLV bearing hBD-2 cDNA was introduced into SCID mouse submandibular glands via cannulation. Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry or enzyme-linked immunosorbent assay (ELISA) were performed to detect hBD-2 expression in glands or in saliva. Candida albicans 613p was inoculated orally into SCID mice to establish oral candidiasis. Whilst expression of hBD-2 was detected in mouse salivary glands by RT-PCR and immunohistochemistry 1 day or 1 week following delivery of lentivirus, hBD-2 was not detected in saliva. There was recoverable C. albicans from the oral cavity and gastrointestinal tract 4 days to 4 weeks after infection, but there was no establishment of observable oral candidiasis in SCID mice under a stereomicroscope. Our data indicate that lentiviral vectors transduce mouse salivary glands, but not at a sufficient level to allow hBD-2 detection in saliva. Other vectors for gene transduction and additional treatment of SCID mice to establish oral candidiasis are needed in order to utilise mouse salivary glands to test antimicrobial gene therapy.
Asunto(s)
Antiinfecciosos/farmacología , Candida albicans/efectos de los fármacos , Retroviridae/efectos de los fármacos , Saliva/metabolismo , Conductos Salivales/metabolismo , beta-Defensinas/farmacología , Animales , Antiinfecciosos/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Regulación de la Expresión Génica/fisiología , Terapia Genética , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Mucosa Bucal/metabolismo , Retroviridae/genética , Saliva/química , Conductos Salivales/química , Conductos Salivales/inmunología , Conductos Salivales/patología , beta-Defensinas/genética , beta-Defensinas/uso terapéuticoRESUMEN
Inverted ductal papilloma (IDP) is a type of ductal papilloma arising in ducts of minor salivary glands. Very few cases, and no cases in Japan, have been reported. Reported herein is a case of IDP with a review of the literature. The patient was a 49-year-old man presenting with a lump in the right buccal mucosa of the premolar area of the mandible. The tumor was excised en bloc after a biopsy diagnosis of IDP. On the surface of the covering epithelium, an opening was seen to be filled with mucinous material. On cut surface the opening led to the tumor cavity. The major portion of the tumor parenchyma was made up of papillary proliferation of basaloid squamous cells. Some crypts, microcysts, and mucous cells were seen. There were no findings suggestive of a malignant tumor. The patient's postoperative course was uneventful and there has been no recurrence after 1 year's follow up. Immunohistochemical analysis of the present case supports the hypothesis that IDP originates from squamous metaplasia and proliferation of minor salivary gland duct cells.