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BACKGROUND: This study aimed to investigate the differentiation of ameloblastic-like cells and the nature of the secreted eosinophilic materials in adenomatoid odontogenic tumors. METHODS: We studied histological and immunohistochemical characteristics of 20 cases using: cytokeratins 14 and 19, amelogenin, collagen I, laminin, vimentin, and CD34. RESULTS: Rosette cells differentiated into ameloblastic-like cells positioned face-to-face, displaying collagen I-positive material between them. Epithelial cells of the rosettes can differentiate into ameloblastic-like cells. This phenomenon probably occurs due to an induction phenomenon between these cells. The secretion of collagen I is probably a brief event. Amelogenin-positive areas were interspersed by epithelial cells in the lace-like areas, outside the rosettes and distant from the ameloblastic-like cells. CONCLUSIONS: There are at least two types of eosinophilic material in different areas within the tumor, one in the rosette and solid areas and another in lace-like areas. The secreted eosinophilic material in the rosettes and solid areas is probably a product of well-differentiated ameloblastic-like cells. It is positive for collagen I and negative for amelogenin, whereas some eosinophilic materials in the lace-like areas are positive for amelogenin. We hypothesize that the latter eosinophilic material could be a product of odontogenic cuboidal epithelial or intermediate stratum-like epithelial cells.
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Ameloblastoma , Proteínas do Esmalte Dentário , Tumores Odontogênicos , Humanos , Amelogenina , Tumores Odontogênicos/patologia , Imuno-Histoquímica , Ameloblastoma/patologia , Células Epiteliais/patologia , Colágeno , Diferenciação CelularRESUMO
Pleomorphic adenoma (PA) is the most common salivary gland neoplasm and, although mostly benign, recurrences, being called recurrent pleomorphic adenoma (RPA) and malignant transformation to carcinoma ex pleomorphic adenoma (CXPA), do occur. Recently, attention has been focused on molecular targeted cancer therapy in various tumors, including salivary gland tumors. The aim of this study was to investigate the role of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) in PA, RPA, and CXPA. In total, 20 cases of PA, 18 of RPA, and 7 cases of CXPA were immunohistochemically studied for ER, PR, and HER-2. For evaluation of ER and PR, only nuclear expression and greater than 10% positive cells were regarded as cutoff criteria. HER-2 was evaluated semiquantitatively and graded from 0 to 3+. HER-2 amplification was assessed by chromogenic in situ hybridization (CISH). Tumors were negative for ER, PR, and HER-2 in all cases of PA and RPA. A case of CXPA showed moderate and complete membranous staining, and 6 cases were negative. HER-2 amplification was not observed in any case. In conclusion, the lack of ER, PR, and HER-2 expression in PA, RPA, and CXPA suggests that these proteins are not involved in progression, recurrence, or malignant transformation of PA.
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Primordial odontogenic tumor (POT) is a benign mixed odontogenic tumor comprised of a loose connective tissue with a similar morphology with dental papilla and exhibiting in its periphery the presence of a columnar epithelium. POT occurs in young patients and typically is associated with an unerupted tooth, with the mandible being the main anatomic site of occurrence. The present manuscript is aimed at describing a new case of POT and reviewing the main biologic findings related to this odontogenic tumor.
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Differential diagnosis among fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias is difficult, since there is considerable overlap of histologic features, but also extremely important, since they differ greatly in etiology, clinical behaviour, prognosis and terapeuthic approach. There is no data about the use of immunohistochemistry, a viable and accessible technique, for this purpose. The objective of this study was to investigate, comparatively, the immunohistochemical expression of major non-collagenous proteins (osteonectin [ON], osteopontin [OP], bone sialoprotein [BSP] and osteocalcin [OC]) of mineralized tissue extracellular matrix in 22 cases of fibrous dysplasias, 16 of cemento-ossifying fibromas and 16 of cemento-osseous dysplasias. ON maintained the same expression profile in all cases; the staining for OP was negative in fusiform cells producing cementoid globules and weak, as well as heterogeneous, in high mineralized matrixes; there was negativity for BSP in cementoid globules and in the fusiform cells that produce them, differently from the strong positive expression found in the majority of bone trabeculae and their peripheral cuboidal osteoblasts; and finally, the immuno-reactivity for OC was weak, except in cuboidal osteoblasts and osteocytes. We can conclude that the nature of mineralized structure and the cellular phenotype are much more responsible for variability in immunohistochemical profile than the type of lesion (fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias) which makes difficult, at least for a while, the use of these proteins with diagnosis purpose.
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Cementoma/diagnóstico , Fibroma Ossificante/diagnóstico , Displasia Fibrosa Óssea/diagnóstico , Sialoproteína de Ligação à Integrina/metabolismo , Osteocalcina/metabolismo , Osteonectina/metabolismo , Osteopontina/metabolismo , Osso e Ossos/patologia , Cementoma/metabolismo , Cementoma/patologia , Diagnóstico Diferencial , Fibroma Ossificante/metabolismo , Fibroma Ossificante/patologia , Displasia Fibrosa Óssea/metabolismo , Displasia Fibrosa Óssea/patologia , HumanosRESUMO
OBJECTIVES: This study aimed to revisit benign odontogenic ghost cell lesions (BOGCL) by hematoxylin and eosin staining and immunohistochemistry. MATERIALS AND METHODS: Thirty cases of calcifying odontogenic cyst (COC) and 6 cases of dentinogenic ghost cell tumor (DGCT) were selected for histopathological and immunohistochemical analysis. Sections stained for cytokeratin (K) 14, K-19, amelogenin, collagen type 1 (COL-1), and dentin matrix acidic phosphoprotein 1 (DMP-1) were evaluated using qualitative analysis. Sections stained for Ki-67 and minichromosome maintenance protein-2 (MCM-2) were evaluated using semi-quantitative analysis. RESULTS: A morphologic overlap was noticed in all BOGCL. Moreover, no differences were detected in the expression of K-14 and K-19. The expression of proliferative markers Ki-67 and MCM-2 was similar between cystic and tumor lesions (p > .05). The presence of COL-1 and absence of amelogenin in the so-called dysplastic dentin, associated with its histologic pattern, suggest that this is in fact an enameloid-like tissue. CONCLUSIONS: The dysplastic dentin should be considered an enameloid-like tissue in these lesions. CLINICAL RELEVANCE: The similarity in histology, protein expression, and proliferative marker indices between COC and DGCT suggest that they are a sole entity and likely represent types of the same neoplasia.
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Dentina , Cisto Odontogênico Calcificante , Tumores Odontogênicos , Colágeno Tipo I , Humanos , QueratinasRESUMO
BACKGROUND: Adenoid cystic carcinoma (ACC) is a salivary gland malignancy with poor long-term survival, which warrants studies aimed at clarifying the pathogenesis of this disease in order to widen the scope of therapeutic options currently available. Alterations in regulatory mechanisms relating to vascular support, cell death and autophagy are important pathways for tumor growth in cancer. Thus, the present study aimed to access vascular supply, apoptosis, autophagy and cell senescence in ACC of minor salivary glands. METHODS: We analyzed 25 cases of minor salivary gland ACC by immunohistochemistry using anti-CD34, anti-CD105, anti-D2-40, anti-Bax, anti-Bcl-2, anti-Beclin-1, anti-LC3B, anti-p21 and anti-p16. RESULTS: Microvessel density was low and based on anti-CD34, anti-CD105 and anti-D2-40 immunostaining. There was positivity for anti-CD34, anti-Bcl-2, anti-Beclin, anti-LC3B and anti-p21 and a positive correlation between Bcl-2 and Beclin (p = 0.014). CONCLUSIONS: Our results showed that ACC does not depend on neo-angiogenesis and is probably associated to anti-apoptotic, autophagic and anti-senescence events.
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Apoptose/fisiologia , Autofagia/fisiologia , Carcinoma Adenoide Cístico/patologia , Senescência Celular/fisiologia , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The present study aimed to compare the expression of p63/p40 with smooth muscle actin (SMA) and vimentin (VIM) by myoepithelial cells in minor salivary gland tumors. Fifty-two formalin-fixed paraffin-embedded samples of minor salivary gland tumors derived from intercalated duct (pleomorphic adenoma [PA], adenoid cystic carcinoma [ACC], epithelial-myoepithelial carcinoma [EMC], polymorphous adenocarcinoma [PAC], and secretory carcinoma [SC]) and 3 samples of minor salivary gland tumors derived from excretory duct (mucoepidermoid carcinoma [MEC]) were evaluated by means of immunohistochemistry. The data were analyzed qualitatively. The results indicated that p63 and p40 expression were detected in myoepithelial cells present in PA, ACC, and EMC. However, both proteins were also observed in squamous areas of PA and all cases of MEC. SMA were noticed in some myoepithelial cells of PA, ACC, and EMC. Expression of SMA was negative in the other salivary gland tumors evaluated. VIM was constantly expressed by myoepithelial cells in PA, ACC, and EMC. VIM was also observed in cells of PAC and SC, but not in squamous areas of PA and MEC. In conclusion, p63 expression is almost comparable with VIM in detecting myoepithelial cells, an immunolabeling pattern not followed by p40, and consequently, caution has to be taken during the interpretation of salivary gland tumor exhibiting an p63/p40 phenotype in order to avoid a misdiagnosis.
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Biomarcadores Tumorais/metabolismo , Carcinoma/patologia , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Actinas/análise , Actinas/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma/diagnóstico , Diagnóstico Diferencial , Células Epiteliais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/diagnóstico , Glândulas Salivares Menores/citologia , Fatores de Transcrição/análise , Proteínas Supressoras de Tumor/análise , Vimentina/análise , Vimentina/metabolismo , Adulto JovemRESUMO
The aim of the present study was to analyze the in vitro effect of various doses of epidermal growth factor (EGF; 5 and 10 ng/ml) on matrix metalloproteinase-2 (MMP-2) secretion and E-cadherin/ß-catenin expression by co-cultured cells that mimic an in situ carcinoma ex-pleomorphic adenoma, where benign myoepithelial cells from a pleomorphic adenoma surround malignant epithelial cells. EGF was supplemented in various doses and the effects were evaluated following four days of cell culture. ELISA was performed to determine MMP-2 secretion levels. Gene expression for E-cadherin and ß-catenin was analyzed using quantitative polymerase chain reaction. The results revealed that E-cadherin expression decreased when the cells were supplemented with 5 ng/ml EGF. ELISA results indicated that MMP-2 secretion increased when EGF was supplemented at concentrations of 5 and 10 ng/ml. The present findings demonstrated that EGF may be involved in the epithelial-mesenchymal transition process via altering the E-cadherin/ß-catenin complex and increasing MMP-2 secretion, which may then favor the dissolution of the basement membrane to the benefit of malignant cell clusters, contributing to the development of an invasive phenotype in this in vitro model of tumorigenesis.
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There is mounting evidence on the importance of some biological processes in tumor growth, such as vascular supply, apoptosis, autophagy, and senescence. We have investigated these processes in polymorphous low-grade adenocarcinoma (PLGA), in an attempt to identify those that are relevant for this particular lesion. We analyzed 31 cases of PLGA using immunohistochemistry to antibodies against CD34 and CD105 to detect blood vessels; against D2-40 to detect lymphatic vessels; against Bax, Bcl-2, and survivin to explore cell apoptosis; and against Beclin and LCB3 to investigate autophagy and against p21 and p16 to assess senescence. Our results showed that PLGA growth does not depend on newly formed vessels but only on preexisting vasculature. Furthermore, PLGA is promoted by autophagy, sustained by both anti-apoptotic and anti-senescence signals, and stimulated by Bcl-2 and survivin.
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Adenocarcinoma/patologia , Neoplasias Bucais/patologia , Neovascularização Patológica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/fisiologia , Autofagia/fisiologia , Biomarcadores Tumorais/análise , Proliferação de Células/fisiologia , Senescência Celular/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Polymorphous low-grade adenocarcinoma (PLGA) remains a diagnostic challenge for most pathologists due to its large spectrum of histological patterns. In this study, the expression of two new markers recently described for salivary gland tumors was studied in PLGA. METHODS: The morphology of 33 cases of PLGA was carefully evaluated using hematoxylin-and-eosin-stained sections and confirmed by immunohistochemistry for cytokeratin 7, vimentin, and S-100. Periodic acid-Schiff with diastase digestion was also used. The expression of mammaglobin and DOG-1 was carried out using the EnVision System. Mammaglobin was assessed according to the percentage of positively stained tumor cells, while DOG-1 was evaluated according to its presence and site. For MCM-2 and Ki-67, markers of proliferation, the labeling index of cell nuclei positivity was evaluated using total cell number. The ETV6-NTRK3 fusion was examined by fluorescence in situ hybridization analysis. RESULTS: The histological patterns of the tumor were classified as lobular or non-lobular. For the non-lobular pattern, tubular, cribriform, glomeruliform, trabecular, and papillary patterns were observed. Mammaglobin was present in all PLGA cases, and its expression was stronger (P = 0.01) in the lobular than in the non-lobular pattern. The expression of DOG-1 was present in the apical portion and cytoplasm of the cells. Proliferation markers were low for all cases independent of histological pattern. CONCLUSIONS: Polymorphous low-grade adenocarcinoma has been confirmed to originate from the intercalated duct and to feature high expression of mammaglobin in its lobular pattern resembling that of mammary secretory analogue carcinoma, except for the ETV6 gene rearrangement.