RESUMEN
Cancer develops in a multi-step process where environmental carcinogenic exposure is a primary etiological component, and where cell-cell communication governs the biological activities of tissues. Identifying the molecular genes that regulate this process is essential to targeting metastatic breast cancer. Ionizing radiation can modify and damage DNA, RNA, and cell membrane components such as lipids and proteins by direct ionization. Comparing differential gene expression can help to determine the effect of radiation and estrogens on cell adhesion. An in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line MCF-10F to low doses of high linear energy transfer α particle radiation and subsequent growth in the presence of 17ß-estradiol. The MCF-10F cell line was analyzed in different stages of transformation that showed gradual phenotypic changes including altered morphology, increase in cell proliferation relative to the control, anchorage-independent growth, and invasive capability before becoming tumorigenic in nude mice. This model was used to determine genes associated with cell adhesion and communication such as E-cadherin, the desmocollin 3, the gap junction protein alpha 1, the Integrin alpha 6, the Integrin beta 6, the Keratin 14, Keratin 16, Keratin 17, Keratin 6B, and the laminin beta 3. Results indicated that most genes had greater expression in the tumorigenic cell line Tumor2 derived from the athymic animal than the Alpha3, a non-tumorigenic cell line exposed only to radiation, indicating that altered expression levels of adhesion molecules depended on estrogen. There is a significant need for experimental model systems that facilitate the study of cell plasticity to assess the importance of estrogens in modulating the biology of cancer cells.
Asunto(s)
Neoplasias de la Mama , Ratones , Animales , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Queratina-14 , Queratina-16 , Transformación Celular Neoplásica/genética , Ratones Desnudos , Desmocolinas , Queratina-17 , Queratina-6 , Laminina , Estrógenos/farmacología , Radiación Ionizante , Moléculas de Adhesión Celular , Estradiol/farmacología , Cadherinas/genética , ARN , Conexinas , Lípidos , ADN , Adhesión CelularRESUMEN
OBJECTIVE: To investigate whether the process of primary gingival keratinocytes culture obtained from normal human gingiva modifies the expression of keratins (K) 10, K14, and K19. DESIGN: Human gingival fragments were collected from healthy individuals in the same oral site. One part of the samples underwent an immunohistochemistry assay for K10, K14, and K19. The labeling in the epithelium was quantified using a semiautomated method. Another part was used for primary gingival keratinocytes isolation and growth in two-dimensional culture. These cells were also stained for K10, K14, and K19 using immunofluorescence and immunocytochemistry. Positive cells were counted, and the nuclei and cytoplasmatic labeling areas were quantified. RESULTS: In the gingival tissue, a higher expression was found for K14 versus K10 (pâ¯<â¯0.001); K19 was negative in all samples. In gingival keratinocytes culture, K14 (89.6 %) had the highest expression with significant differences in relation to K10 (76.9 %, pâ¯<â¯0.01) and K19 (9.9 %, pâ¯<â¯0.01). The cells positive for K14 exhibited larger nuclei in comparison with K10 (pâ¯<â¯0.05) and K19 (pâ¯<â¯0.05), suggesting a more undifferentiated phenotype. K19 cells showed the largest cytoplasmatic labeling in relation to K10- (pâ¯<â¯0.05) and K14-positive (pâ¯<â¯0.05) cells. CONCLUSION: The process of growth in culture of gingival keratinocytes maintained the expression pattern of K10 and K14 observed in gingival tissues. However, this method induces the expression of K19, suggesting a potential transformation of the keratin network presented in the gingival keratinocytes during the formation of a monolayer in vitro. This reflects the dynamics of cell differentiation.
Asunto(s)
Encía/metabolismo , Queratinocitos/metabolismo , Queratinas/metabolismo , Diferenciación Celular , Células Cultivadas , Epitelio , Encía/citología , Humanos , Queratina-14RESUMEN
Epidermal differentiation is a complex process in which keratinocytes go through morphological and biochemical changes in approximately 15 to 30 days. Abnormal keratinocyte differentiation is involved in the pathophysiology of several skin diseases. In this scenario, mesenchymal stem cells (MSCs) emerge as a promising approach to study skin biology in both normal and pathological conditions. Herein, we have studied the differentiation of MSC from umbilical cord into keratinocytes. MSC were cultured in Dulbecco's modified Eagle's medium (DMEM) (proliferation medium) and, after characterization, differentiation was induced by culturing cells in a defined keratinocyte serum-free medium (KSFM) supplemented with epidermal growth factor (EGF) and calcium chloride ions. Cells cultivated in DMEM were used as control. Cultures were evaluated from day 1 to 23, based on the cell morphology, the expression of p63, involucrin and cytokeratins (KRTs) KRT5, KRT10 and KRT14, by quantitative polymerase chain reaction, Western blot analysis or immunofluorescence, and by the detection of epidermal kallikreins activity. In cells grown in keratinocyte serum-free medium with EGF and 1.8 mM calcium, KRT5 and KRT14 expression was shown at the first day, followed by the expression of p63 at the seventh day. KRT10 expression was detected from day seventh while involucrin was observed after this period. Data showed higher kallikrein (KLK) activity in KSFM-cultured cells from day 11th in comparison to control. These data indicate that MSC differentiated into keratinocytes similarly to that occurs in the human epidermis. KLK activity detection appears to be a good methodology for the monitoring the differentiation of MSC into the keratinocyte lineage, providing useful tools for the better understanding of the skin biology.
Asunto(s)
Epidermis/metabolismo , Calicreínas/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Western Blotting , Cloruro de Calcio/farmacología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Células Cultivadas , Factor de Crecimiento Epidérmico/metabolismo , Epidermis/efectos de los fármacos , Técnica del Anticuerpo Fluorescente , Humanos , Inmunofenotipificación , Queratina-10/genética , Queratina-10/metabolismo , Queratina-14/genética , Queratina-14/metabolismo , Queratina-5/genética , Queratina-5/metabolismo , Microscopía , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismoRESUMEN
BACKGROUND: Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. AIMS: In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). METHODS: We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. RESULTS: Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. CONCLUSION: In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients.
Asunto(s)
Clorfeniramina/farmacología , Dermatitis Fototóxica/metabolismo , Antagonistas de los Receptores Histamínicos H1/farmacología , Prometazina/farmacología , Células 3T3 , Animales , Clorfeniramina/efectos adversos , Dermatitis Fototóxica/etiología , Dermatitis Fototóxica/prevención & control , Dinoprostona/metabolismo , Femenino , Histamina/metabolismo , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Humanos , Interleucina-1/metabolismo , Queratina-14/metabolismo , Leucotrieno B4/metabolismo , Ratones , Persona de Mediana Edad , FN-kappa B/metabolismo , Prometazina/efectos adversos , Precursores de Proteínas/metabolismo , Piel/metabolismo , Crema para la Piel/efectos adversos , Fenómenos Fisiológicos de la Piel/efectos de los fármacos , Canales Catiónicos TRPV/metabolismo , Técnicas de Cultivo de Tejidos , Rayos Ultravioleta/efectos adversos , betaendorfina/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to investigate the influence of smoking on the methylation and hydroxymethylation status of global DNA and specific sites of KRT14, KRT19, miR-9-3 and miR-137 genes in the healthy oral mucosa. METHODS: Samples of oral epithelial cells were collected using mouthwash from a population of former and current smokers and those who had never smoked. Genomic DNA was extracted, and global DNA methylation and hydroxymethylation was performed using an ELISA-based technique; DNA methylation at specific sites was performed using Methylation-Specific PCR (MSP) (KRT14, miR-9-3 and miR-137) or Methylation-Sensitive Restriction Enzymes (MSRE) (KRT19). K14 and K19 protein expression was analysed by immunohistochemistry. RESULTS: Higher levels of global DNA methylation were found in current smokers with over 15 years of consumption (p=0.04), but no differences were found in relation to global DNA hydroxymethylation. No differences in global DNA methylation and hydroxymethylation levels were found in relation to age or gender. Global DNA methylation was higher than the hydroxymethylation level (p<0.001) but they were not correlated in the oral mucosa. For specific sites, miR-9-3 hypomethylation was detected in current smokers (p<0.001). Additional analysis showed no difference in the methylation status when age, gender, period of consumption or amount of cigarettes were considered for any of the studied genes. K19 expression was higher in current smokers in comparison to former smokers and those who had never smoked (p<0.05). CONCLUSION: We concluded that smoking habits were capable of inducing changes in global DNA methylation, miR-9-3 methylation status and K19 expression.
Asunto(s)
Metilación de ADN , Queratina-19/genética , MicroARNs/genética , Mucosa Bucal/metabolismo , Fumar/genética , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Queratina-14/genética , Queratina-14/metabolismo , Queratina-19/metabolismo , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
Epithelial migration plays a central role in development, wound repair and tumor metastasis, but the role of intermediate filament in this important event is unknown. We showed recently that vimentin coexists in the same cell with keratin-KRT14 at the leading edge of the migrating epidermal cells, and knockdown of vimentin impaired colony growth. Here we demonstrate that vimentin co-localizes and co-immunoprecipitates with keratin-KRT14, and mutations in the -YRKLLEGEE- sequence of vimentin significantly reduced migration of the keratinocytes. Our data demonstrates that keratinocyte migration requires the interaction between vimentin and keratins at the -YRKLLEGEE- sequence at the helical 2B domain of vimentin. These findings have broad implications for understanding the roles of vimentin intermediate filaments in normal and neoplastic epithelial cells.
Asunto(s)
Células Epiteliales/citología , Proteínas de Filamentos Intermediarios/metabolismo , Queratina-14/metabolismo , Vimentina/metabolismo , Secuencia de Aminoácidos , Anticuerpos Monoclonales/inmunología , Movimiento Celular , Células Cultivadas , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal , Silenciador del Gen , Humanos , Proteínas de Filamentos Intermediarios/química , Queratina-14/química , Queratina-14/inmunología , Queratinocitos/metabolismo , Unión Proteica , Vimentina/química , Vimentina/genéticaRESUMEN
AIMS: The diagnosis of polymorphous low-grade adenocarcinoma (PLGA) remains difficult for general pathologists, particularly in cases of small biopsy samples. We aimed to characterize the histopathological spectrum and immunohistochemical aspects by using an accessible immunohistochemical panel of cytoskeletal proteins in limited samples of PLGA. METHODS AND RESULTS: Forty-six patients diagnosed with PLGA in incisional biopsies were identified retrospectively. Seventy-two per cent of patients were women and 28% were men, with a mean age of 55 years. The palate was the most affected site. Grossly, the mean size of the samples was 0.8 cm and 74% of specimens were fragmented. All tumours characteristically displayed the microscopic features of architecturally diverse patterns, infiltrative areas and low-grade cytology. Neoplastic cells were diffusely positive to cytokeratin (CK) 7, vimentin and S100 protein, but only focally positive to CK14 and negative to α-smooth muscle actin (α-SMA), thus lacking myoepithelial differentiation. CONCLUSIONS: Microscopic recognition of PLGA is facilitated by a characteristic combination of multiple architectural patterns of growth, infiltration of adjacent tissues and cytological aspects. These features are present even in small biopsy samples. The association of histopathological aspects with CK7, CK14, vimentin, S100 and α-SMA immunoexpression is helpful in reaching the diagnosis of doubtful cases.
Asunto(s)
Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/metabolismo , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/metabolismo , Actinas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Algoritmos , Biopsia , Femenino , Humanos , Inmunohistoquímica , Queratina-14/metabolismo , Queratina-7/metabolismo , Queratinas/metabolismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Proteínas S100/metabolismo , Neoplasias de las Glándulas Salivales/patología , Vimentina/metabolismoRESUMEN
Gastrointestinal stromal tumor is the most common clinically significant mesenchymal neoplasm of the gastrointestinal tract. The expression of the intermediate filament cytokeratin in gastrointestinal stromal tumor is not frequently reported in the literature. The aim of this study was to investigate the immunohistochemical expression of several types of cytokeratin in a large number of cases (n=687), including a pan-cytokeratin marker (AE1/AE3 cocktail antibodies), high-molecular weight cytokeratins (34ßE12 antibody), and individual cytokeratins 8 (35ßH11 and CAM5.2 antibodies), 7, 14, and 20. Ki-67 antigen was used for the determination of cell proliferation index, and the correlation between Ki-67 and cytokeratin expression was evaluated. Cytokeratin expression was also correlated with several clinicopathologic parameters. The expression of pan-cytokeratin was observed in 24 (3.5%) cases, with variable intensity. Only 1 of 687 (0.1%) cases showed cytokeratin 14 expression. All 687 cases revealed no expression of high-molecular weight cytokeratins, cytokeratins 7, 8, and 20. No significant statistical association was found between AE1/AE3 immunoreactivity and several clinicopathologic parameters, including sex, tumor location and size, cell morphology, mitotic count, risk of aggressive behavior, and Ki-67 antigen cell proliferation index. However, statistical correlation between AE1/AE3 immunoreactivity and a higher age at diagnosis was detected. These results show that cytokeratin expression is not frequent in gastrointestinal stromal tumor, but caution is necessary to avoid erroneous diagnoses.
Asunto(s)
Biomarcadores de Tumor/biosíntesis , Neoplasias Gastrointestinales , Regulación Neoplásica de la Expresión Génica , Queratina-14/biosíntesis , Queratina-20/biosíntesis , Queratina-7/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antineoplásicos/química , Proliferación Celular , Femenino , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/patología , Humanos , Inmunohistoquímica/métodos , Inmunohistoquímica/normas , Antígeno Ki-67/biosíntesis , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Physiological root resorption differentiates primary from permanent teeth. The understanding of what protects and regulates root resorption might help to develop therapies to its control. AIM: To verify the presence and distribution of ECRM and the expression of CK14, OPG, TRAP and COX-2 in the periodontal ligament (PDL) of human primary and permanent teeth. Design. Eight primary teeth undergoing physiological or pathological root resorption and 4 permanent teeth were immunohistochemically processed for CK14, TRAP, COX-2 and OPG expression. RESULTS: PDL from primary and permanent teeth showed similar morphological features; however, fewer ECRM clusters and higher immunoreactivity to CK14 were found in primary PDL. In permanent teeth, ECRM were distributed along the entire PDL tissue. Howship's lacunae were found only in primary teeth, associated with the presence of TRAP-positive cells and increase in COX-2 expression. OPG expression in primary PDL was detected in nonresorptive cervical areas and in lacunae showing reparative tissue. It was observed higher expression of OPG in all permanent teeth when compared to primary specimens. CONCLUSIONS: It may be concluded that PDL from primary teeth shows less ECRM clusters and lower expression of OPG. These features may be associated with lower protection against root resorption in primary teeth.
Asunto(s)
Ligamento Periodontal/metabolismo , Resorción Radicular/prevención & control , Diente Primario/fisiología , Fosfatasa Ácida/biosíntesis , Fosfatasa Ácida/genética , Adulto , Niño , Preescolar , Ciclooxigenasa 2/biosíntesis , Ciclooxigenasa 2/genética , Dentición Permanente , Células Epiteliales/fisiología , Expresión Génica , Humanos , Isoenzimas/biosíntesis , Isoenzimas/genética , Queratina-14/biosíntesis , Queratina-14/genética , Osteoprotegerina/biosíntesis , Osteoprotegerina/genética , Resorción Radicular/metabolismo , Resorción Radicular/fisiopatología , Fosfatasa Ácida Tartratorresistente , Diente Primario/citología , Adulto JovenRESUMEN
BACKGROUND: Oral spindle cell carcinoma (SpCC) is a rare variant of oral squamous cell carcinoma (SCC). The aims of this study were to compare the clinicopathologic and immunohistochemical features of oral SpCC with conventional oral SCC. METHODS: Five cases of oral SpCC and 10 cases of oral SCC (five well-differentiated and five poorly differentiated) were evaluated through conventional hematoxylin and eosin staining and immunohistochemical reactions to cytokeratins (CK), vimentin, desmin, smooth muscle actin, muscle-specific actin, S-100 protein, epithelial membrane antigen (EMA), p53, and ki-67. RESULTS: Oral SpCC showed predilection for males on their sixth decade of life, presenting clinically as painful infiltrative ulcers or ulcerated exophytic polypoid masses, preferably located on the alveolar mucosa. Mesenchymal markers were expressed in the spindle cell but not in the carcinomatous component of SpCC, and it was negative in all SCC. CKs AE1/AE3, 6, 14, and EMA were positive on both carcinomatous and spindle cell components of most SpCCs. These tumors also presented higher p53 and ki-67 expression and no CK 1 expression in contrast to well-differentiated SCC. CONCLUSION: Oral SpCC presented a different clinical profile than conventional SCC and histopathologic features and p53 and ki-67 expression closer to poorly differentiated SCC. Besides mesenchymal markers, CK AE1/AE3, 6, 14, and EMA expression on spindle cells may be useful as an adjunct on microscopical differential diagnosis of SpCC.
Asunto(s)
Carcinoma/patología , Neoplasias de la Boca/patología , Actinas/análisis , Adulto , Factores de Edad , Anciano , Carcinoma de Células Escamosas/patología , Desmina/análisis , Femenino , Humanos , Inmunohistoquímica , Queratina-13/análisis , Queratina-14/análisis , Queratina-6/análisis , Queratina-8/análisis , Queratinas/análisis , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Mucina-1/análisis , Proteínas S100/análisis , Factores Sexuales , Proteína p53 Supresora de Tumor/análisis , Vimentina/análisisRESUMEN
Dentinogenic ghost cell tumor (DGCT) is a rare neoplasm, representing 1.9% to 2.1% of all odontogenic tumors. Few cases of DGCT have been reported and only 11 show no bone involvement. A rare case of peripheral DGCT is reported, located in the anterior mandible of a 45-year-old man. The patient presented a slow painless growth in the canine region of an edentulous mandible. Radiographically, no bone involvement was registered. The lesion was enucleated and microscopically characterized by islands of epithelial cells showing ameloblastomalike features in fibrous tissue. Dysplasic dentin and ghost cells were frequently observed. Areas showing a connection between tumor cells and the overlying mucosa were also identified. Immunohistochemical analysis demonstrated positivity for pan-cytokeratin, cytokeratin-14, and 2 neural markers. Denditric cells (Langerhans cells and melanocytes) were identified inside tumoral islands. A rare case of peripheral DGCT is reported, with immunohistochemical analysis and a review of the English literature.
Asunto(s)
Dentina/patología , Neoplasias Mandibulares/patología , Tumores Odontogénicos/patología , Arco Dental/patología , Displasia de la Dentina/patología , Humanos , Arcada Edéntula/patología , Queratina-14/análisis , Queratinas/análisis , Células de Langerhans/patología , Masculino , Melanocitos/patología , Persona de Mediana Edad , Proteínas S100/análisisRESUMEN
This case report describes a 10-year-old female patient with an adenomatoid odontogenic tumor developing together with a cystic complex odontoma. This occurrence is considered very unusual. Immunohistochemical detection of cytokeratins AE1/AE3, CK5, CK8, CK10, CK14, CK19 and Ki-67 was performed.
Asunto(s)
Neoplasias Mandibulares/patología , Neoplasias Primarias Múltiples/patología , Tumores Odontogénicos/patología , Odontoma/patología , Niño , Femenino , Humanos , Queratina-1/análisis , Queratina-10/análisis , Queratina-14/análisis , Queratina-19/análisis , Queratina-3/análisis , Queratina-5/análisis , Queratina-8/análisis , Antígeno Ki-67/análisisRESUMEN
Sebaceous carcinoma (SC) is a rare malignancy, affecting mainly the periocular glands. To the best of the authors' knowledge, this is the first English-language report of parotid SC affecting children; two cases are presented. Immunohistochemical studies included 29 different antibodies (15 of these were cytokeratins, CKs). For each case, DNA ploidy status was determined using isolated nuclei stained with Feulgen and analysed using a DNA image cytometry system. Most of the tumour cells were positive for CKs AE1/AE3, 34B12, 5 and 7. The CK14 pattern depicted the monolayer of basal cells surrounding the islands of malignant tissue, while the more central sebaceous differentiated cells were negative. Epithelial membrane antigen was strongly positive in the well differentiated cells, while most of the basaloid peripheral cells were negative, and only a few cells were positive for carcinoembryonic antigen. beta catenin, E cadherin and C-erb B2 were expressed by most of the cells including the more differentiated sebaceous cells. Tumour cells were negative for muscle or myoepithelial markers, androgen, oestrogen and progesterone receptors. Both SCs were uniformly diploid, and showed low proliferative indices for p53, Ki-67 and Mcm-2, which is consistent with the good clinical course presented by these patients so far.
Asunto(s)
Adenocarcinoma Sebáceo/química , Neoplasias de la Parótida/química , Adenocarcinoma Sebáceo/genética , Adenocarcinoma Sebáceo/patología , Cadherinas/análisis , Niño , Diploidia , Femenino , Humanos , Queratina-14/análisis , Queratina-18/análisis , Queratina-19/análisis , Masculino , Mucina-1/análisis , Neoplasias de la Parótida/genética , Neoplasias de la Parótida/patología , Pronóstico , Receptor ErbB-2/análisis , beta Catenina/análisisRESUMEN
BACKGROUND: Cyclosporine is a potent immunosupressor, which induces cytokeratin expression pattern changes and dermal dendrocytes number increase. OBJECTIVES: To evaluate its clinical effect in psoriasis, on keratinocytic proliferation and differentiation, and on dermal dendrocytes proliferation. METHODS: Thirty patients with psoriasis were treated and evaluated for 8 weeks. Clinical improvement was evaluated by Psoriasis Area and Severity Index (PASI). Biopsies were performed initially and after 8 weeks. Immunohistochemistry [CK markers 10, 14, and 16, and factor XIIIa+ (FXIIIa+)] was performed. RESULTS: Mean PASI before treatment was 26.32 and 3.71 after. Mean initial and final PASI difference was 22.61 (p < 0.001). Two patients had serum creatinine and six uric acid increase. Before and after treatment, mean numbers per field of dermal dendrocytes were 7.07 and 3.68, respectively. Mean difference was 3.39, with p < 0.001. CK10 immunohistochemical pattern demonstrated recovery of normal expression pattern in 26 patients, while CK14 pattern demonstrated improvement in 21 patients. CONCLUSIONS: Cyclosporine was effective and safe for psoriasis in low doses, with significant decrease of PASI and dermal dendrocytes number after 8 weeks of therapy. CK10 and 14 pattern changed and, less prominently, CK16 expression. These modifications occur later than the PASI and dermal dendrocytes variation.
Asunto(s)
Ciclosporina/uso terapéutico , Células Dendríticas/patología , Dermis/patología , Inmunosupresores/uso terapéutico , Queratinocitos/patología , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Adulto , Anciano , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclosporina/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Inmunosupresores/administración & dosificación , Queratina-10/metabolismo , Queratina-14/metabolismo , Queratina-16/metabolismo , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
INTRODUCTION AND METHODS: We performed an immunohistochemical study in four cases of myopitheliomas with objective to realize a profile in respect of differentiation grade by the monoclonal antibodies CK14, vimentin and alph-SMA, besides to investigate the cell proliferation by anti-PCNA, besides, we compare the immunoreactive with glandular normal tissue. RESULTS: In the glandular normal tissue the myoepithelials cells had shown expression for alpha-SMA and CK 14, while that in the ductals cells, only the presence of CK 14 was verified. All the cases was verified positivity for CK 14 and vimentin, however, CK 14 had been present only in epithelioid and fusiform cells, while that the vimentin revealed positive also in the cytoplasm of the plasmocytoid cells. alpha-SMA was not detected in the neoplasic cells. Immunopositivity for the PCNA was observed in more than 75% of the cellular component of the analyzed tumors, independent of the cellular type. CONCLUSIONS: We concluded that it did not have difference in the proliferative activity among the cellular types presents in the myoepitheliomas and, still, the results of this study suggest that the constituent cells of this neoplasia one really represent cells of the mioepitelial ancestry, but in different stages of differentiation.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Transformación Celular Neoplásica/patología , Mioepitelioma/patología , Neoplasias de las Glándulas Salivales/patología , Actinas/metabolismo , Adulto , Anciano de 80 o más Años , Transformación Celular Neoplásica/metabolismo , Femenino , Humanos , Inmunohistoquímica , Queratina-14/metabolismo , Masculino , Mioepitelioma/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Neoplasias de las Glándulas Salivales/metabolismo , Glándulas Salivales Menores/patología , Vimentina/metabolismoRESUMEN
OBJECTIVE: The aim of this work was to study cytokeratin (Ck) expression in initial radiation-induced oral mucositis. STUDY DESIGN: Eleven cases of initial radiomucositis of the buccal mucosa and 9 normal specimens were immunostained for Ck 1, 5, 6, 7, 8, 10, 14, 16, 18, and 19 by immunoperoxidase method. RESULTS: Expression of Ck 1, 6, 10, and 16 was stronger in mucositis than in normal mucosa. Ck 7, 8, and 18 were negative for both control and study groups. Ck 5, 13, and 14 were positive for both groups, nevertheless suprabasal staining for Ck 14 was more evident in mucositis than in the control group. Sporadic staining for Ck 19 was observed in 1 case of mucositis and in 2 controls. CONCLUSIONS: Increased Ck expression can be associated with the reactive proliferation of the epithelium and increasing resistance of the oral mucosa during the initial phases of radiotherapy.
Asunto(s)
Irradiación Craneana/efectos adversos , Queratinas/biosíntesis , Mucositis/metabolismo , Traumatismos por Radiación/metabolismo , Estomatitis/metabolismo , Adulto , Femenino , Humanos , Técnicas para Inmunoenzimas , Queratina-1 , Queratina-10 , Queratina-14 , Queratina-16 , Queratina-6 , Masculino , Persona de Mediana Edad , Mucositis/etiología , Mucositis/patología , Dosificación Radioterapéutica , Estomatitis/etiología , Estomatitis/patologíaRESUMEN
AIMS: To characterize the cellular component in pleomorphic adenoma (PA) that undergoes malignant transformation in carcinoma ex pleomorphic adenoma (CXPA). METHODS AND RESULTS: A panel of antibodies against cytoskeletal proteins was applied in 16 cases of CXPA: intracapsular carcinoma (five cases), minimally invasive (four cases) and frankly invasive (seven cases). The CXPAs were classified into two main groups according to their predominant cellular component as detected by the panel of antibodies: (i) carcinomas with only epithelial differentiation (75% of the cases), and (ii) carcinomas with a myoepithelial component (25%). CXPA with only epithelial differentiation showed two types of malignant areas in the part of the tumour that was confined by the PA capsule: (i) intraductal carcinoma areas characterized by ductal structures containing both benign myoepithelial cells positive for alpha-smooth muscle actin (alpha-SMA), vimentin and cytokeratin (CK)14 and proliferating atypical luminal cells reactive for CK7, CK8 and CK19, and (ii) carcinoma areas composed only of epithelial cells reactive for CK7, CK8 and CK19. In the latter, the cells presented morphological and immunohistochemical characteristics similar to those found in areas of invasive carcinoma outside the PA capsule. CXPAs with a myoepithelial component were composed mainly or exclusively of cells that expressed vimentin and alpha-SMA. In this group, ductal structures reminiscent of PA filled by malignant cells were not identified. CONCLUSION: Most CXPAs consist only of epithelial cells that have an immunoprofile comparable to ductal luminal cells of PA. These malignant luminal cells arise in the duct-like structures as intraductal carcinoma and probably only at this early stage of development should the lesion be considered as a non-invasive carcinoma.
Asunto(s)
Adenocarcinoma/patología , Adenoma Pleomórfico/patología , Biomarcadores de Tumor/análisis , Actinas/análisis , Adenocarcinoma/metabolismo , Adenoma Pleomórfico/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Queratina-14 , Queratina-7 , Queratinas/análisis , Masculino , Persona de Mediana Edad , Músculo Liso/química , Vimentina/análisisRESUMEN
Neoplasms and tumours related to the odontogenic apparatus may be composed only of epithelial tissue or epithelial tissue associated with odontogenic ectomesenchyme. The immunohistochemical detection of different cytokeratins (CKs) polypeptides and vimentin has made it easier to explain the histogenesis of many epithelial diseases. The present study aimed to describe the immunohistochemical expression of cytokeratins 7, 8, 10, 13, 14, 18, 19 and vimentin in the epithelial components of the dental germ and of five types of odontogenic tumours. The results were compared and histogenesis discussed. All cells of the dental germ were positive for CK14, except for the preameloblasts and secreting ameloblasts, in which CK14 was gradually replaced by CK19. CK7 was especially expressed in the cells of the Hertwig root sheath and the stellate reticulum. The dental lamina was the only structure to express CK13. The reduced epithelium of the enamel organ contained CK14 and occasionally CK13. Cells similar to the stellate reticulum, present in the ameloblastoma and in the ameloblastic fibroma, were positive for CK13, which indicates a nature other than that of the stellate reticulum of the normal dental germ. The expression of CK14 and the ultrastructural aspects of the adenomatoid odontogenic tumour probably indicated its origin in the reduced dental epithelium. Calcifying odontogenic epithelial tumour is thought to be composed of primordial cells due to the expression of vimentin. Odontomas exhibited an immunohistochemical profile similar to that of the dental germ. In conclusion, the typical IF of odontogenic epithelium was CK14, while CK8, 10 and 18 were absent. Cytokeratins 13 and 19 labelled squamous differentiation or epithelial cells near the surface epithelium, and CK7 had variable expression.
Asunto(s)
Queratinas/análisis , Tumores Odontogénicos/química , Ameloblastoma/química , Tejido Conectivo/química , Órgano del Esmalte/química , Células Epiteliales/química , Humanos , Inmunohistoquímica , Filamentos Intermedios/química , Queratina-10 , Queratina-14 , Queratina-7 , Queratina-8 , Odontoma/química , Germen Dentario/química , Vimentina/análisisRESUMEN
OBJECTIVE: Orthokeratinized odontogenic cyst (OOC) is a developmental cyst that occurs in the maxilla and the mandible and is defined by the World Health Organization as the uncommon orthokeratinized type of odontogenic keratocyst (OKC). However, studies have shown that OOC has peculiar clinicopathologic aspects and biologic behavior when compared with other developmental odontogenic cysts, especially OKCs. Therefore, in this study, the immunohistochemical profile of the OOC was delineated and compared with that of the OKC. STUDY DESIGN: Twelve cases of OOC were submitted to a panel of antibodies composed of cytokeratins (10, 13, and 14) and extracellular matrix proteins: fibronectin, types I and III collagen, and tenascin. For comparative means, 12 cases of OKC also were submitted to the same panel of antibodies. RESULTS: The results obtained showed that OOCs expressed cytokeratin 10 and showed variable expression of cytokeratins 13 and 14. Fibronectin and collagen types I and III also were expressed in OOC in a fibrillar aspect. OKC showed only the superficial keratin layer positive to cytokeratin 10 and the basal and suprabasal layers with variable expression of cytokeratin 14, and cytokeratin 13 was present in the upper epithelial layers. The extracellular matrix proteins showed a nonfibrillar expression. Tenascin was immunoexpressed only in OKC. CONCLUSION: The immunohistochemical profile of the studied cysts clearly showed that OOC presents a well-formed cystic enveloping, whereas the OKC profile is compatible with a more aggressive biologic behavior.