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BACKGROUND: The aims of this study were to determine intra (ILVD) and peritumoral (PLVD) lymphatic vessel density (LVD), and to investigate the relationship of LVD with occult metastasis and prognosis. METHODS: Eighty-seven oral squamous cell carcinomas, in clinical stages I or II, arising in the tongue or floor of the mouth were stained with podoplanin. Lymphatic vessels were quantified in intra and peritumoral areas by sequential analysis and hot spot evaluation. Associations of the ILVD and PLVD with clinicopathologic parameters were determined by Chi-square or Fisher's exact test. The 5 and 10-year survival rates were calculated by the Kaplan-Meier and compared using the log-rank test. RESULTS: No significant association was observed between ILVD or PLDV and clinicopathologic variables including occult lymph node metastasis, or clinical follow-up. However, ILVD showed a significant association with regional recurrence (p = 0.040). The perineural invasion was associated with PLVD (p = 0.041). Disease-specific (p = 0.044) and disease-free survivals (p = 0.016) had significant association with PLVD. CONCLUSIONS: The intra or peritumoral lymphatic vessel density had no predictive value for occult lymph node metastasis in the early stages of oral cancer arising in the tongue or floor of mouth.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Vasos Linfáticos , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Humanos , Metástase Linfática , Vasos Linfáticos/patologia , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Ki-67 has shown promise as a prognostic factor in pulmonary carcinoids. In this study, we sought to validate the importance of Ki-67 and study the relationships between Ki-67 and other stromal biomarkers of vascular density. We examined Ki-67, CD34, and D2-40 in tumor tissues from 128 patients with surgically excised typical carcinoid of the lung. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for cellular proliferation (Ki-67), microvascular density (CD34-MVD), and D2-40 lymphovascular density. The main outcome was overall survival, considered as life expectancy until death from metastasis. Specimens from patients with central tumors showed high CD34-MVD (P = .01), which was also significantly associated with a compromised surgical margin, lymph node metastasis, and clinical stage Ib. Equally significant was high D2-40 lymphovascular density in central specimens with a compromised surgical margin and lymph node metastasis. A high Ki-67 proliferation rate was significantly associated with tumors from patients with clinical stage IIb, IIIa, and IV disease. Multivariate Cox model analysis demonstrated that tumor location and stage, surgical margin, tumor size, and N stage were significantly related to survival time (P < .05). Quantitative staining of the tumor for Ki-67 and CD34-MVD served as prognostic factors (P < .05), which were more relevant than the surgical and pathological stage. Ki-67 greater than 5% and CD34-MVD greater than 7% staining comprise a subset of patients with higher death hazard; this outcome may harbor evidence for further prospective studies of target therapy after surgical resection.
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Anticorpos Monoclonais Murinos/imunologia , Antígenos CD34/análise , Capilares/química , Tumor Carcinoide/química , Proliferação de Células , Imunoquímica/métodos , Antígeno Ki-67/análise , Neoplasias Pulmonares/química , Linfangiogênese , Vasos Linfáticos/química , Neovascularização Patológica , Adolescente , Adulto , Idoso , Capilares/patologia , Tumor Carcinoide/mortalidade , Tumor Carcinoide/secundário , Tumor Carcinoide/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Vasos Linfáticos/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Carga Tumoral , Adulto JovemRESUMO
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is primarily a locoregional disease in which the cervical lymph nodes are the chief site of metastasis. The purpose of this study was to examine the relationship between lymphangiogenesis and clinicopathological aspects of HNSCC and its metastasis. METHODS: Fifty-two patients with HNSCC and metastatic lymph nodes from 21 of these subjects were analyzed by immunohistochemistry. RESULTS: The HNSCC samples were predominantly negative for vascular endothelial growth factor (VEGF)-C, VEGF-D, and vascular endothelial growth factor receptor (VEGFR)3. There was an association between the density of lymph vessels (measured by D2-40 staining) in the lymph nodes and advanced-stage tumors. There was no link between the expression of these proteins and survival rates. CONCLUSION: Although lymphatic spread is a significant event in the progression of HNSCC, the expression of VEGF-C, VEGF-D, and VEGFR3 does not correlate with clinicopathological characteristics, suggesting that other signaling pathways mediate lymphangiogenesis in HNSCC.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/secundário , Linfangiogênese , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imuno-Histoquímica , Metástase Linfática , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. .
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Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/secundário , Vasos Linfáticos/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma Mucinoso/química , /análise , Diagnóstico Diferencial , Imuno-Histoquímica , Queratinas/análise , Metástase Linfática , Vasos Linfáticos/química , Glicoproteínas de Membrana/análise , Proteínas de Membrana/análise , Mucinas/análise , Neoplasias Ovarianas/química , Valores de Referência , Análise Serial de Tecidos , Carga Tumoral , Biomarcadores Tumorais/análiseRESUMO
INTRODUCTION: Endoscopic submucosal dissection (ESD) of early neoplasias of the gastrointestinal tract (GIT) has been increasingly applied as an alternative to invasive surgical procedures, with the aim to preserve the patient's organ and quality of life, although it does not allow the histopathological analysis of lymph nodes. Previous studies demonstrated that the presence of neoplastic emboli in lymphatic (lymphatic vascular invasion [LVI]) or blood vessels (blood vascular invasion [BVI]) is considered a positive predictive factor for the occurrence of lymph node metastasis. The assessment of vascular invasion carried out only by routine hematoxylin and eosin staining (HE) may yield both falsepositive and false-negative results. D2-40 is a specific monoclonal antibody to the lymphatic endothelium. Thus, it is useful for identifying LVI and distinguishing if tumor embolization is found in blood or lymphatic vessels. OBJECTIVE: To determine the role of immunohistochemistry (IHC) in the assessment of ESD specimens by comparing the detection of LVI and BVI by HE and IHC with D2-40 and CD34 immunolabeling. METHOD: We conducted the IHC study using D2-40 and CD34 markers (pan-endothelial) in 30 cases of ESD with histological diagnosis of carcinoma in order to assess the presence of LVI and BVI. RESULTS: The detection of LVI was more prevalent than BVI. Three out of six cases with LVI were false-positive by HE and six were false-negative by IHC. Regarding BVI, five cases were identified and one was false-negative by IHC. CONCLUSION: Our results indicated that the histopathological analysis of ESD specimens by exclusively routine HE staining does not allow proper evaluation of BVI or LVI.
INTRODUÇÃO: A dissecção endoscópica da submucosa (DES) de neoplasias precoces do trato gastrointestinal (TGI) tem sido cada vez mais aplicada como alternativa aos procedimentos cirúrgicos invasivos, visando a preservar o órgão e a qualidade de vida do paciente, contudo, não possibilita a avaliação histopatológica de linfonodos. Estudos anteriores demonstraram que a presença de êmbolos neoplásicos, em vasos linfáticos (invasão vascular linfática [IVL]) ou sanguíneos (invasão vascular sanguínea [IVS]), é considerada um fator preditivo positivo para ocorrência de metástase linfonodal. A avaliação da invasão vascular realizada apenas pela coloração de rotina hematoxilina e eosina (HE) pode gerar resultados falso-positivos e falso-negativos. O D2-40 é um anticorpo monoclonal específico para endotélio linfático, sendo, portanto, útil para identificar IVL e distinguir se a embolização tumoral encontra-se em vasos sanguíneos ou linfáticos. OBJETIVO: Determinar o papel do estudo imuno-histoquímico (IHQ) na avaliação de espécimes de DES, comparando a detecção de IVL e IVS, pelo HE e IHQ com marcação por D2-40 e CD34. MÉTODO: Foi realizado estudo IHQ utilizando os marcadores D2-40 e CD34 (pan-endotelial) em 30 casos de produtos de DES com diagnóstico histológico de carcinoma para avaliar a presença de IVL e IVS. RESULTADOS: A detecção de IVL foi maior que a de IVS. Dos seis casos com IVL ao HE, três eram falso-positivos e seis, falso-negativos à IHQ. Em relação à IVS, foram identificados cinco casos falsopositivos e um falso-negativo à IHQ. CONCLUSÃO: Nossos resultados indicaram que a análise histopatológica dos produtos de DES realizando apenas a coloração HE não permite a avaliação adequada da presença de IVS ou IVL.
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AIM: To evaluate and compare detection of lymphatic and blood vessel invasion (LVI and BVI) by hematoxylin-eosin (HE) and immunohistochemistry (IHC) in gastric cancer specimens, and to correlate with lymph node status. METHODS: IHC using D2-40 (a lymphatic endothelial marker) and CD34 (a pan-endothelial marker) was performed to study LVI and BVI in surgical specimens from a consecutive series of 95 primary gastric cancer cases. The results of the IHC study were compared with the detection by HE using McNemar test and kappa index. The morphologic features of the tumors and the presence of LVI and BVI were related to the presence of lymph node metastasis. A χ(2) test was performed to obtain associations between LVI and BVI and other prognostic factors for gastric cancer. RESULTS: The detection rate of LVI was considerably higher than that of BVI. The IHC study identified eight false-positive cases and 13 false-negative cases for LVI, and 24 false-positive cases and 10 false-negative cases for BVI. The average Kappa value determined was moderate for LVI (κ = 0.50) and low for BVI (κ = 0.20). Both LVI and BVI were statistically associated with the presence of lymph node metastasis (HE: P = 0.001, P = 0.013, and IHC: P = 0.001, P = 0.019). The morphologic features associated with LVI were location of the tumor in the distal third of the stomach (P = 0.039), Borrmann's macroscopic type (P = 0.001), organ invasion (P = 0.03) and the depth of tumor invasion (P = 0.001). The presence of BVI was related only to the depth of tumor invasion (P = 0.003). CONCLUSION: The immunohistochemical identification of lymphatic and blood vessels is useful for increasing the accuracy of the diagnosis of vessel invasion and for predicting lymph node metastasis.
Assuntos
Técnicas de Preparação Histocitológica/métodos , Linfonodos/patologia , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Anticorpos Monoclonais Murinos/metabolismo , Antígenos CD34/metabolismo , Biomarcadores Tumorais/metabolismo , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Linfonodos/metabolismo , Metástase Linfática , Masculino , Neovascularização Patológica/metabolismo , Prognóstico , Neoplasias Gástricas/metabolismoRESUMO
Introdução: A análise citológica dessas efusões é importante para o diagnóstico, principalmente de malignidades, embora apresente baixa sensibilidade. A diferenciação entre os diversos tipos neoplásicos na citologia de efusões torna necessária a investigação de um painel imunocitoquímico válido, incluindo novos anticorpos como MOC-31 e D2-40. Estes anticorpos auxiliam na diferenciação entre mesoteliomas e carcinomas, enquanto que outros anticorpos, de imunorreatividade conhecida para a espécie canina, como a vimentina, a citoqueratina AE1/AE3, o CD3 e o CD79cy, auxiliam na detecção de sarcomas e linfomas. O objetivo deste estudo foi padronizar e incluir os marcadores imunocitoquímicos MOC-31 e D2-40 em um painel mínimo, que permita defi nir o tipo neoplásico em efusões caninas.Materiais, Métodos e Resultados: Quatorze amostras de efusões neoplásicas caninas foram obtidas do atendimento clínico do Hospital de Clínicas Veterinárias da UFRGS. Após a análise, os sedimentos das amostras foram fi xados em solução de formalina tamponada 10%, formando um pellet celular. Estes foram incluídos em parafi na e processados pelas técnicas histológicas de rotina. Aos cortes citológicos de cada amostra foram aplicadas as técnicas de imunocitoquímica (ICQ) pelo método estreptavidina-biotina ligada à peroxidase, para os anticorpos primários anti-citoqueratina, anti-vimentina, D2-40 e MOC-31. Pa
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Introdução: A análise citológica dessas efusões é importante para o diagnóstico, principalmente de malignidades, embora apresente baixa sensibilidade. A diferenciação entre os diversos tipos neoplásicos na citologia de efusões torna necessária a investigação de um painel imunocitoquímico válido, incluindo novos anticorpos como MOC-31 e D2-40. Estes anticorpos auxiliam na diferenciação entre mesoteliomas e carcinomas, enquanto que outros anticorpos, de imunorreatividade conhecida para a espécie canina, como a vimentina, a citoqueratina AE1/AE3, o CD3 e o CD79cy, auxiliam na detecção de sarcomas e linfomas. O objetivo deste estudo foi padronizar e incluir os marcadores imunocitoquímicos MOC-31 e D2-40 em um painel mínimo, que permita defi nir o tipo neoplásico em efusões caninas.Materiais, Métodos e Resultados: Quatorze amostras de efusões neoplásicas caninas foram obtidas do atendimento clínico do Hospital de Clínicas Veterinárias da UFRGS. Após a análise, os sedimentos das amostras foram fi xados em solução de formalina tamponada 10%, formando um pellet celular. Estes foram incluídos em parafi na e processados pelas técnicas histológicas de rotina. Aos cortes citológicos de cada amostra foram aplicadas as técnicas de imunocitoquímica (ICQ) pelo método estreptavidina-biotina ligada à peroxidase, para os anticorpos primários anti-citoqueratina, anti-vimentina, D2-40 e MOC-31. Pa
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OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6 percent) cases, with 29/31 (93.5 percent) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9 percent vs. 22.6 percent, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5 percent vs. 21.6 percent, respectively. In 27/143 (18.8 percent) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5 percent vs. 3.7 percent, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.
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Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/secundário , Glicoproteínas de Membrana/análise , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo do Útero/metabolismo , Análise de Variância , Fibroblastos/metabolismo , Fibroblastos/patologia , Metástase Linfática , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence) in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer) were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis) and D2-40 (marker for lymphatic endothelium). Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 µm²; P = 0.019) and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041) when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Adenomatosos/patologia , Neoplasias Colorretais/patologia , Linfangiogênese/fisiologia , Neovascularização Patológica/patologia , Pólipos Adenomatosos/irrigação sanguínea , Pólipos Adenomatosos/química , Anticorpos Monoclonais/análise , Antígenos CD/análise , Biomarcadores/análise , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/química , Imuno-Histoquímica , Vasos Linfáticos/química , Vasos Linfáticos/patologia , Microcirculação , Estudos Retrospectivos , Receptores de Superfície Celular/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.