RESUMO
BACKGROUND: The histogenesis of neoplastic spindle cells of Kaposi's sarcoma is still uncertain, but some studies consider it a lymphatic vessel differentiation. Prox-1 is a nuclear transcription factor that plays a major role during embryonic lymphangiogenesis, and it has been considered a specific and sensitive lymphatic endothelial cell marker. The aim of this study was to determine the expression of Prox-1 in oral Kaposi's sarcoma comparing the results with oral benign vascular tumors including capillary hemangiomas and pyogenic granulomas. METHODS: Expression of Prox-1 and HHV-8 was evaluated by immunohistochemistry in 30 oral Kaposi's sarcoma, 5 oral capillary hemangiomas, and 10 oral pyogenic granulomas. The labeling index was expressed as the percentage of positive cells for each case studied. Statistical comparison was performed using the Wilcoxon-Mann-Whitney rank sum test. RESULTS: Twenty-eight (93.3%) and 30 oral Kaposi's sarcoma cases were positive for Prox-1 and HHV-8, respectively, while all oral benign vascular tumors were negative for these markers. The number of Prox-1 and HHV-8 oral Kaposi's sarcoma-positive cells increased significantly from patch/plaque to nodular histological stages. CONCLUSION: The expression of Prox-1 in the neoplastic spindle cells supports the view of a lymphatic differentiation in oral Kaposi's sarcoma. Prox-1 may also be involved in the pathogenesis of oral Kaposi's sarcoma as the number of positive spindle cells increased progressively from patch to nodular stages and could be eventually useful as an additional diagnostic tool for differential diagnosis between oral Kaposi's sarcoma and benign oral vascular lesions.
Assuntos
Proteínas de Homeodomínio/análise , Neoplasias Bucais/patologia , Sarcoma de Kaposi/patologia , Proteínas Supressoras de Tumor/análise , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Diferenciação Celular , Proliferação de Células , Criança , Endotélio Linfático/patologia , Feminino , Doenças da Gengiva/patologia , Granuloma Piogênico/patologia , Soropositividade para HIV/patologia , Hemangioma Capilar/patologia , Herpesvirus Humano 8/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/virologia , Sarcoma de Kaposi/virologia , Doenças da Língua/patologia , Neoplasias da Língua/patologia , Adulto JovemRESUMO
When examining microscopically lymph nodes removed as part of the surgical therapy for thyroid carcinoma, one should be aware of the fact that high endothelial venules, when dilated and near the capsule, can lead to a wrong diagnosis of metastasis. We present a case in which such a situation arose.
Assuntos
Adenocarcinoma Papilar/patologia , Endotélio Linfático/patologia , Linfonodos/patologia , Vasos Linfáticos/patologia , Nódulo da Glândula Tireoide/patologia , Criança , Feminino , Humanos , Metástase Linfática/patologia , TireoidectomiaRESUMO
BACKGROUND: Loco-regional spread of disease causes high morbidity and is associated with the poor prognosis of malignant oral tumors. Better understanding of mechanisms underlying the establishment of lymph node metastasis is necessary for the development of more effective therapies for patients with oral cancer. The aims of this work were to evaluate a possible correlation between endothelial cell Bcl-2 and lymph node metastasis in patients with oral squamous cell carcinoma (OSCC), and to study signaling pathways that regulate Bcl-2 expression in lymphatic endothelial cells. METHODS: Endothelial cells were selectively retrieved from paraffin-embedded tissue sections of primary human OSCC from patients with or without lymph node metastasis by laser capture microdissection. RT-PCR was used to evaluate Bcl-2 expression in tumor-associated endothelial cells and in tumor cells. In vitro, mechanistic studies were performed to examine the effect of vascular endothelial growth factor (VEGF)-C on the expression of Bcl-2 in primary human lymphatic endothelial cells. RESULTS: We observed that Bcl-2 expression is upregulated in the endothelial cells of human oral tumors with lymph node metastasis as compared to endothelial cells from stage-matched tumors without metastasis. VEGF-C induced Bcl-2 expression in lymphatic endothelial cells via VEGFR-3 and PI3k/Akt signaling. Notably, OSCC cells express VEGF-C and induce Bcl-2 in lymphatic endothelial cells. CONCLUSIONS: Collectively, this work unveiled a mechanism for the induction of Bcl-2 in lymphatic endothelial cells and suggested that endothelial cell Bcl-2 contributes to lymph node metastasis in patients with oral squamous cell carcinoma.
Assuntos
Carcinoma de Células Escamosas/secundário , Células Endoteliais/patologia , Endotélio Linfático/patologia , Metástase Linfática/patologia , Neoplasias Bucais/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Biomarcadores Tumorais/análise , Western Blotting , Carcinoma de Células Escamosas/patologia , Células Cultivadas , Cromonas/farmacologia , Células Endoteliais/efeitos dos fármacos , Endotélio Linfático/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/farmacologia , Proteína Oncogênica v-akt/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fator C de Crescimento do Endotélio Vascular/farmacologia , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacosRESUMO
Tonsillar polyps are nonneoplastic lesions usually composed of variable amounts of lymphoid and vascular and connective tissues. All of them are generally assumed to be hamartomatous proliferations, but the profile of vascular and connective components has yet to be explored. The vascular system of the tonsils is complex and includes highly specialized structures (i.e., high endothelial venules (HEVs)) involved in lymphocyte homing into lymphoid tissues. In 14 tonsillar polyps and 26 control tonsils, an immunohistochemical study was performed using CD34 (blood vessels and HEVs), MECA-79 (HEVs), D2-40 (lymphatic vessels), Ki-67, collagens I and III, fibronectin, and tenascin-C. The polyps showed increased total lymphatic area, whereas the number of blood vessels and lymphatics and the blood vascular area did not differ significantly from those of control tonsils. Rare Ki-67+ endothelial cells were found. In the polyps, we detected, possibly for the first time, HEVs amid lymphoid tissue, and that the amount of the latter correlated positively with HEV density. The polyps also presented lesser amounts of fibronectin and collagens I and III than in normal tonsils, which were distributed in a disorganized fashion. Tenascin-C expression was uncommon in the polyps and control tonsils. Tonsillar polyps are composed of disorganized connective tissue and lymphatic channels which can be considered hamartomatous proliferations. However, the lymphoid component is possibly reactive due to its relationship with the HEVs. The highly differentiated phenotype of the HEVs and their complex biology are not in agreement with what would be expected for a component of hamartomatous nature.
Assuntos
Endotélio Linfático/patologia , Tonsila Palatina/patologia , Pólipos/patologia , Células Estromais/patologia , Adolescente , Adulto , Biomarcadores/metabolismo , Criança , Endotélio Linfático/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tonsila Palatina/metabolismo , Tonsila Palatina/cirurgia , Pólipos/metabolismo , Pólipos/cirurgia , Células Estromais/metabolismo , Tonsilectomia , Vênulas/metabolismo , Vênulas/patologia , Adulto JovemRESUMO
BACKGROUND: The origin of spindle cells (SC) in oral Kaposi's sarcoma (OKS) is still an intriguing aspect. Thus the aim of the present study was to compare the clinical, histological and immunohistochemical characteristics of OKS and oral pyogenic granuloma (OPG), in order to contribute to the knowledge of the cells involved in Kaposi's sarcoma pathogenesis. METHODS: In this retrospective, observational and comparative study, 39 OKS and 30 OPG cases were included. Immunohistochemical studies were performed for vimentin, alpha SMA, desmin, C-kit, CD34, D2-40 and LANA-1 [human herpesvirus-8(HHV-8)]. Statistical comparisons were done using the chi-square and Wilcoxon-Mann-Whitney rank sum tests. RESULTS: Fourteen (35.9%) OKS cases also affected the skin, and 83.8% involved the palate. All OKS and OPG were positive for vimentin and CD34. OKS samples were positive for alpha SMA, and 25.6% expressed C-kit. All OKS cases were positive for HHV-8, and the number of positive cells increased significantly from early / intermediate to late histological stage. D2-40 was expressed in the cellular component and vascular walls of all OKS cases, but it was negative in OPG. HHV-8 expression was increased in late histological stages of OKS lesions. CONCLUSIONS: The expression of D2-40 marker in the vascular walls and SC supports the view of a lymphatic differentiation in neoplastic cells of OKS. Desmin, alpha SMA, D2-40, C-kit and HHV-8 were the main markers differently expressed in OKS and OPG.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Endotélio Linfático/patologia , Neoplasias Bucais/patologia , Sarcoma de Kaposi/patologia , Actinas/análise , Adulto , Idoso , Anticorpos Monoclonais/análise , Anticorpos Monoclonais Murinos , Antígenos CD34/análise , Diferenciação Celular , Linhagem da Célula , Desmina/análise , Granuloma Piogênico/metabolismo , Granuloma Piogênico/patologia , Herpesvirus Humano 8/isolamento & purificação , Humanos , Técnicas Imunoenzimáticas , Masculino , México , Pessoa de Meia-Idade , Doenças da Boca/metabolismo , Doenças da Boca/patologia , Neoplasias Bucais/química , Neoplasias Bucais/complicações , Neoplasias Bucais/virologia , Proteínas Proto-Oncogênicas c-kit/análise , Estudos Retrospectivos , Sarcoma de Kaposi/química , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/virologia , Vimentina/análiseRESUMO
BACKGROUND: Studies of lymphatic vessels were limited by the lack of specific markers. Recently, they have become possible due to the release of new D2-40 antibody, a selective marker for lymphatic endothelium. The aim of our study was to compare neoplastic invasion in lymphatic and blood vessels detected in hematoxylin and eosin (H&E) and immunohistochemistry-stained sections. METHODOLOGY: A total of 123 cases of invasive mammary carcinomas were studied and sorted out into three subgroups according to axillary staging (macrometastasis, micrometastasis and lymph node negative). Lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) were initially evaluated in histological H&E and immunohistochemistry-stained sequential sections. Lymphatic and blood vessel invasions were assessed by immunohistochemistry, employing D2-40 and CD31 antibodies, respectively. LVI and BVI were related to size, type, histologic grade of primary tumors, and the presence of metastasis. RESULTS: LVI was detected through H&E staining procedure in 17/123 cases (13.8 percent), and through immunohistochemistry procedure in 35/123 cases (28.5 percent) (kappa = 0.433). BVI was detected through H&E in 5/123 cases (4.1 percent), and through immunohistochemistry in 19/123 cases (15.4 percent) (kappa = 0.198). LVI and BVI were positively related to higher histologic grade of primary tumors (p < 0.05). LVI was also positively related to the presence of macrometastasis. CONCLUSION: The detection of lymphatic and blood vessel invasions through immunohistochemistry employing D2-40 and CD31 was higher than the detection through H&E, and it was related to higher tumor grade and metastasis in axillary lymph nodes.
INTRODUÇÃO: Estudos de vasos linfáticos eram limitados pela ausência de marcadores endoteliais linfáticos específicos. Recentemente, eles se tornaram possíveis após liberação comercial do novo anticorpo D2-40, marcador seletivo para endotélio linfático. O objetivo do nosso estudo foi comparar invasão neoplásica em vasos linfáticos e sanguíneos detectada em secções coradas pela hematoxilina e eosina (HE) e imuno-histoquímica (IIQ). MATERIAIS E MÉTODOS: Foram estudados 123 casos de carcinomas mamários invasores subdivididos em três subgrupos de acordo com o estadiamento axilar: macrometástases (Mac-Met), micrometástases (Mic-Met) e linfonodo negativo (LNN). Invasão de vasos linfáticos (IVL) e de vasos sangüíneos (IVS) foi inicialmente avaliada em secções histológicas coradas pela HE e através da IIQ realizada em cortes seqüenciais. A invasão de vasos linfáticos e sanguíneos foi avaliada pela imuno-histoquímica, empregando-se respectivamente os anticorpos D2-40, e CD31. IVL e IVS foram relacionadas com tamanho tumoral, tipo e grau histológico dos tumores primários e com a presença de metástases. RESULTADOS: IVL foi observada pela HE em 17/123 casos (13,8 por cento) e pela IIQ em 35/123 casos (28,5 por cento) (kappa = 0,433). IVS foi observada pela HE em 5/123 casos (4,1 por cento) e pela IIQ em 19/123 casos (15,4 por cento) (kappa = 0,198). IVL e IVS estavam positivamente relacionadas com maior grau histológico dos tumores primários (p < 0,05). IVL também estava positivamente relacionada com a presença de macrometástases. CONCLUSÃO: A detecção IIQ, respectivamente por D2-40 e CD31, de invasão de vasos linfáticos e sanguíneos foi maior que a detecção feita em cortes corados pela HE e relacionou-se com maior grau tumoral e metástases em linfonodos axilares.