Podoplanin and VEGF-C immunoexpression in oral squamous cell carcinomas: prognostic significance.

BACKGROUND: This study evaluated the clinical significance of podoplanin and vascular endothelial growth factor-C (VEGF-C) expression in oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: The immunohistochemical expression of podoplanin and VEGF-C were investigated in 42 well-differentiated OSCCs. The Chi-square test was used to analyze the association of biomarker expression with the clinical characteristics, treatment, and outcome, as well as with histopathological microscopic features and histopathological malignancy index. The relationship between podoplanin, VEGF-C and prognosis was also studied. Survival rates were calculated by the Kaplan Meier method. RESULTS: Strong podoplanin expression was associated with male gender (p=0.037) and with early clinical stage (I-II) (p=0.027). Strong podoplanin expression was more frequently found in patients with perineural infiltration. Podoplanin and VEGF-C expression were not significant prognostic factors for patients with OSCC. CONCLUSION: These results suggest that the strong podoplanin and VEGF-C expression by malignant cells is associated with perineural invasion in patients with OSCC.

Immunolocalization of podoplanin in benign odontogenic tumours with and without ectomesenchyme.

OBJECTIVES: To investigate podoplanin expression in epithelial odontogenic tumours with and without ectomesenchyme and verify the association between its immunoexpression and proliferative activity in keratocystic odontogenic tumours (KCOTS) and orthokeratinized odontogenic cysts (OOCs). DESIGN: Eight ameloblastomas, nine adenomatoid odontogenic tumours, twenty KCOTS, five OOC, one calcifying epithelial odontogenic tumour, two ameloblastic fibromas, four ameloblastic fibro-odontomas and five calcifying cystic odontogenic tumours were immunohistochemically analysed with anti-podoplanin antibody. For KCOTS and OOC, the cell proliferation index was determined with Ki-67 immunostaining and compared by Spearman correlation coefficient. RESULTS: Podoplanin was expressed in the peripheral odontogenic epithelium of most tumours. Ectomesenchyme was negative, except for odontoblasts. KCOTS exhibited positive podoplanin expression while in OOC it was absent/weak. There was statistically significant correlation (p=0.006) between podoplanin expression and cellular proliferation index of KCOTS and OOC. CONCLUSION: Podoplanin seems to be related to the proliferative activity of KCOTS and may have a role in the process of local invasion of odontogenic tumours with and without ectomesenchyme.

[Effects of chronic alcoholism and alcoholic detoxication on rat submandibular glands: morphometric study]. / Efeitos do alcoolismo crônico e da desintoxicação alcóolica sobre a glândula submandibular de ratos: estudo morfométrico.

This work is a morphometric study of several parenquimatous structures of rats' submandibular gland which were submitted to experimental cronic alcoholism and others which were recovered after detoxication during 30 days. It was used 3 groups (5 rats in each group): Control, Alcoholic and Detoxicated. The fact of alcohol acts in body tissues, take us to believe that changes in the submandibular glands morphology of rats which were submitted to cronic alcoholism can happen. In fact, after alcoholisation and detoxication there is an occurence of significant statistically differences when we confront the 3 groups one another (two by two) in reference to the body weight of the animals (g) and the submandibular gland weight (mg). Usually, occurred a decrease in the alcoholic group and in the detoxicated group as well, towards the control group and a significant increase of the body and gland weight from the detoxicated group in relation to the alcoholic group. Regarding the total volume of the several gland structures evaluated, it was verified significant statistically differences in the acinar and granulous duct compartments, in which the alcoholic and the detoxicated groups presented a smaller total volume than the control group. About the other stereologic parameters evaluated, there was not significant statistically differences among the groups neither among the several gland structures evaluated.

VEGF-C e densidade de vasos linfáticos em carcinoma espinocelular de boca: associação com as metástases linfonodais ocultas e com o prognóstico dos pacientes / VEGF-C and lymphatic vessel density in oral squamous cell carcinoma: association with occult lymph node metastasis and patients prognosis

Este estudo avaliou a densidade vascular linfática (DVL) em relação a expressão do fator de crescimento endotelial vascular-C (VEGF-C) pelas células tumorais, bem como verificou a associação com variáveis clínicas e microscópicas de pacientes portadores de carcinoma espinocelular de boca (CEC). Oitenta e sete pacientes com CECs primários, clinicamente T1N0M0 ou T2N0M0, com metástase linfonodal oculta (pN+) e sem (pN0), foram analisadas após tratamento no Hospital do Câncer A.C. Camargo, São Paulo, Brasil. Amostras dos tumores emblocados em parafina foram seccionadas e coradas com os anticorpos primários anti-podoplanina e anti-VEGF-C humanos. Os vasos linfáticos foram contados nas regiões intratumoral (DLI) e peritumoral (DLP) em vinte campos microscópicos (400X) sequenciais e em cinco campos microscópicos (400X) por hot spot de cada tumor. As médias das densidades linfáticas, intratumoral e peritumoral, foram obtidas isoladamente e usadas como pontos de corte da amostra, dividindo-a em tumores com alta densidade linfática e baixa densidade linfática. As associações entre DLI / DLP e a expressão de VEGF-C ou em relação aos parâmetros clínicos e microscópicos avaliados foram obtidas pelo teste do qui-quadrado ou teste exato de Fisher. As taxas de sobrevidas, acumuladas em cinco e dez anos, foram calculadas pelo método de Kaplan-Meier e comparadas pelo teste log-rank (=5%). Não houve associação estatisticamente significativa entre a expressão de VEGF-C nos CECs de boca e os parâmetros clinicopatológicos avaliados. Os pacientes com alta DLP apresentaram maiores taxas de sobrevida específica por câncer (p=0,044) e sobrevida livre de doença (p=0,016). Houve associação estatística significativa entre a alta DLI e a maior ocorrência de recidiva regional nos pacientes da amostra (p=0,047). Entretanto, a alta DLI não foi suficiente para influenciar a sobrevida livre de doença desses pacientes do ponto de vista estatístico. DLP e DLI não se mostraram fatores...

This study evaluated the lymphatic vesssel density (LVD) in correlation with the vascular endothelial growth factor-C (VEGF-C) expression by tumors cells and with clinical and pathological variables in patients with oral squamous cell carcinomas (OSCC). Eighty-seven patients with primary OSCC, clinically T1N0M0 or T2N0M0, with occult lymph-node metastases (pN+) and without (pN0), were analysed after treated in the A. C. Camargo Cancer Hospital, São Paulo, Brazil. Archived paraffin-embedded tumor specimens were sectioned and stained with anti- human podoplanin and VEGF-C antibodies. Lymphatic vessels were counted in intratumoral (ILVD) and peritumoral (PLVD) areas in twenty sequential high-power fields and in five hot spot high-power fields from each tumor. Average values were obtained and used as cutoff point. The correlations between ILVD/PLVD and VEGF-C expression as well as clinicopathological parameters were obtained by chi-square test or Fishers exact test. The 5 and 10-year survival rates were calculated by the Kaplan-Meier method and compared by log-rank test. No statistically significant difference was found between VEGF-C expression in OSCC in regard to clinicopathological parameters. An association between the ILVD and regional recurrence was found (p=0.047) and the PLVD showed associations with disease-specific survival (p=0.044) and disease-free survival (p=0.016). These findings indicate that high ILVD may influences the regional recurrence in neck lymph nodes of patients with early OSCC, however this data was not enough to influence the disease-free survival of these patients with a statistically significant association. PLVD or ILVD did not show predictive value for occult lymph-node metastases in the early stages of OSCC.

VEGF-C e densidade de vasos linfáticos em carcinoma espinocelular de boca: associação com as metástases linfonodais ocultas e com o prognóstico dos pacientes / VEGF-C and lymphatic vessel density in oral squamous cell carcinoma: association with occult lymph node metastasis and patients prognosis

Este estudo avaliou a densidade vascular linfática (DVL) em relação a expressão do fator de crescimento endotelial vascular-C (VEGF-C) pelas células tumorais, bem como verificou a associação com variáveis clínicas e microscópicas de pacientes portadores de carcinoma espinocelular de boca (CEC). Oitenta e sete pacientes com CECs primários, clinicamente T1N0M0 ou T2N0M0, com metástase linfonodal oculta (pN+) e sem (pN0), foram analisadas após tratamento no Hospital do Câncer A.C. Camargo, São Paulo, Brasil. Amostras dos tumores emblocados em parafina foram seccionadas e coradas com os anticorpos primários anti-podoplanina e anti-VEGF-C humanos. Os vasos linfáticos foram contados nas regiões intratumoral (DLI) e peritumoral (DLP) em vinte campos microscópicos (400X) sequenciais e em cinco campos microscópicos (400X) por hot spot de cada tumor. As médias das densidades linfáticas, intratumoral e peritumoral, foram obtidas isoladamente e usadas como pontos de corte da amostra, dividindo-a em tumores com alta densidade linfática e baixa densidade linfática. As associações entre DLI / DLP e a expressão de VEGF-C ou em relação aos parâmetros clínicos e microscópicos avaliados foram obtidas pelo teste do qui-quadrado ou teste exato de Fisher. As taxas de sobrevidas, acumuladas em cinco e dez anos, foram calculadas pelo método de Kaplan-Meier e comparadas pelo teste log-rank (=5%). Não houve associação estatisticamente significativa entre a expressão de VEGF-C nos CECs de boca e os parâmetros clinicopatológicos avaliados. Os pacientes com alta DLP apresentaram maiores taxas de sobrevida específica por câncer (p=0,044) e sobrevida livre de doença (p=0,016). Houve associação estatística significativa entre a alta DLI e a maior ocorrência de recidiva regional nos pacientes da amostra (p=0,047). Entretanto, a alta DLI não foi suficiente para influenciar a sobrevida livre de doença desses pacientes do ponto de vista estatístico. DLP e DLI não se mostraram fatores...

This study evaluated the lymphatic vesssel density (LVD) in correlation with the vascular endothelial growth factor-C (VEGF-C) expression by tumors cells and with clinical and pathological variables in patients with oral squamous cell carcinomas (OSCC). Eighty-seven patients with primary OSCC, clinically T1N0M0 or T2N0M0, with occult lymph-node metastases (pN+) and without (pN0), were analysed after treated in the A. C. Camargo Cancer Hospital, São Paulo, Brazil. Archived paraffin-embedded tumor specimens were sectioned and stained with anti- human podoplanin and VEGF-C antibodies. Lymphatic vessels were counted in intratumoral (ILVD) and peritumoral (PLVD) areas in twenty sequential high-power fields and in five hot spot high-power fields from each tumor. Average values were obtained and used as cutoff point. The correlations between ILVD/PLVD and VEGF-C expression as well as clinicopathological parameters were obtained by chi-square test or Fishers exact test. The 5 and 10-year survival rates were calculated by the Kaplan-Meier method and compared by log-rank test. No statistically significant difference was found between VEGF-C expression in OSCC in regard to clinicopathological parameters. An association between the ILVD and regional recurrence was found (p=0.047) and the PLVD showed associations with disease-specific survival (p=0.044) and disease-free survival (p=0.016). These findings indicate that high ILVD may influences the regional recurrence in neck lymph nodes of patients with early OSCC, however this data was not enough to influence the disease-free survival of these patients with a statistically significant association. PLVD or ILVD did not show predictive value for occult lymph-node metastases in the early stages of OSCC.

Efeitos do alcoolismo crônico e da desintoxicaçäo alcoólica sobre a glândula submandibular de ratos: estudo morfométrico / Effects of chronic alcoholism and alcoholic detoxication on rat submandibular glands: morphometric study

Este estudo consiste de uma análise morfométrica de diversas estruturas parenquimatosas da glândula submandibular de ratos submetidos ao alcoolismo crônico experimental e de ratos recuperados após 30 dias de desintoxicaçäo. Foram utilizados 3 grupos (5 animais por grupo): Controle, Alcoolizado e Desintoxicado. O fato do álcool atuar nos tecidos corporais, leva-nos a acreditar que possam ocorrer alteraçöes na morfologia da glândula submandibular de ratos submetidos ao alcoolismo crônico. De fato, após os processos de alcoolizaçäo e desintoxicaçäo há ocorrência de diferenças estatisticamente significantes quando confrontamos os 3 grupos entre si (dois a dois) no que se refere à massa corpórea dos animais (g) e da glândula submandibular (mg), ocorrendo, normalmente, uma reduçäo tanto do grupo alcoolizado quanto do grupo desintoxicado em relaçäo ao grupo controle e um significante aumento das massas corpórea e glandular do grupo desintoxicado em relaçäo ao grupo alcoolizado. Quanto ao volume absoluto das diversas estruturas glandulares analisadas constatou-se diferenças estatisticamente significantes nos compartimentos acinar e do ducto granuloso, onde os grupos alcoolizado e desintoxicado apresentaram menor volume absoluto em relaçäo ao grupo controle. Quanto aos outros parâmetros estereológicos estudados näo houve diferenças estatisticamente significantes entre os grupos e entre as diversas estruturas glandulares analisadas