Osteosarcoma of the jaw - experience at the Medical University Vienna and comparative study with international tumor registries

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.

Hemolytic, anticancer and antigiardial activity of Palythoa caribaeorum venom

Background Cnidarian venoms and extracts have shown a broad variety of biological activities including cytotoxic, antibacterial and antitumoral effects. Most of these studied extracts were obtained from sea anemones or jellyfish. The present study aimed to determine the toxic activity and assess the antitumor and antiparasitic potential of Palythoa caribaeorum venom by evaluating its in vitro toxicity on several models including human tumor cell lines and against the parasite Giardia intestinalis. Methods The presence of cytolysins and vasoconstrictor activity of P. caribaeorum venom were determined by hemolysis, PLA2 and isolated rat aortic ring assays, respectively. The cytotoxic effect was tested on HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), K562 (human chronic myelogenous leukemia), U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma) and SKLU-1 (human lung adenocarcinoma). An in vivo toxicity assay was performed with crickets and the antiparasitic assay was performed against G. intestinalis at 24 h of incubation. Results P. caribaeorum venom produced hemolytic and PLA2 activity and showed specific cytotoxicity against U251 and SKLU-1 cell lines, with approximately 50% growing inhibition. The venom was toxic to insects and showed activity against G. intestinalis in a dose-dependent manner by possibly altering its membrane osmotic equilibrium. Conclusion These results suggest that P. caribaeorum venom contains compounds with potential therapeutic value against microorganisms and cancer.

Immunological-based approaches for cancer therapy

The immunologic landscape of tumors has been continuously unveiled, providing a new look at the interactions between cancer cells and the immune system. Emerging tumor cells are constantly eliminated by the immune system, but some cells establish a long-term equilibrium phase leading to tumor immunoediting and, eventually, evasion. During this process, tumor cells tend to acquire more mutations. Bearing a high mutation burden leads to a greater number of neoantigens with the potential to initiate an immune response. Although many tumors evoke an immune response, tumor clearance by the immune system does not occur due to a suppressive tumor microenvironment. The mechanisms by which tumors achieve the ability to evade immunologic control vary. Understanding these differences is crucial for the improvement and application of new immune-based therapies. Much effort has been placed in developing in silico algorithms to predict tumor immunogenicity and to characterize the microenvironment via high-throughput sequencing and gene expression techniques. Each sequencing source, transcriptomics, and genomics yields a distinct level of data, helping to elucidate the tumor-based immune responses and guiding the fine-tuning of current and upcoming immune-based therapies. In this review, we explore some of the immunological concepts behind the new immunotherapies and the bioinformatic tools to study the immunological aspects of tumors, focusing on neoantigen determination and microenvironment deconvolution. We further discuss the immune-based therapies already in clinical use, those underway for future clinical application, the next steps in immunotherapy, and how the characterization of the tumor immune contexture can impact therapies aiming to promote or unleash immune-based tumor elimination.

Characterization of reactive stroma in prostate cancer: involvement of growth factors, metalloproteinase matrix, sexual hormones receptors and prostatic stem cells

ABSTRACT Introduction and Objectives: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. Materials and Methods: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: α-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Erα and ERβ. Results: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERα. Conclusions: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells.

International cooperation and health policy implementation in a post-conflict situation: the case of East Timor / Cooperação internacional e formulação de políticas de saúde em situação pós-conflito: o caso do Timor-Leste

This study centers on relationships among national and international actors in preparation of the first health policy document for East Timor, under the United Nations transitional administration, between 1999 and 2002. International cooperation support for the health system rehabilitation process during the post-conflict period is analyzed as part of reconstruction of the State in parallel with construction of the country's political and institutional framework. Knowledge, ideas, "ways of doing," and induced and accepted practices permeate an interplay of power relationships that condition both national political alliance-building and the architecture of international aid, pointing to input to a discussion of how these mechanisms interact at different conjunctures and times in different negotiating frameworks. .

Dedica-se, aqui, às relações entre diferentes atores na elaboração do primeiro documento de política de saúde para o Timor-Leste, sob a administração transitória das Nações Unidas, de 1999 a 2002. O apoio da cooperação internacional no processo de reabilitação do sistema de saúde no período pós-conflito é analisado como parte da reconstrução do Estado e concomitante à construção do arcabouço político e institucional no país. Conhecimentos, ideias, "modos de fazer" e práticas induzidas e aceitas entremeiam um jogo de relações de poder que condiciona tanto a articulação política nacional quanto a arquitetura da ajuda externa, apontando elementos para a discussão de como esses mecanismos se organizam em conjunturas diferentes de negociação.

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC) is evolving, and Carbonic Anhydrase type IX (CA-IX) has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1) overall survival, and 2) with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion). Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS), TNM stage, tumor size (TS), Fuhrman nuclear grade (FNG), microvascular invasion (MVI), peri-renal fat invasion (PFI). We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years). The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790); T stage (p = 0.179); tumor size (p = 0.143); grouped Fuhrman nuclear grade (p = 0.598); microvascular invasion (p = 0.685), and peri-renal fat invasion (p = 0.104). Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma. .

Retroperitoneal sclerosing PEComa with melanin pigmentation and granulomatous inflammation-A rare association within an uncommon tumor.

PEComa, defined as a perivascular epithelioid cell tumor, displays a wide clinicopathological spectrum. Lately, a sclerosing PEComa has been identified as its distinct variant, but with limited documentation, in view of its rarity. Herein, we describe an uncommon case of a 53-year-old lady, who was referred to us with pain abdomen. Radiological imaging disclosed a well-defined, hypodense retroperitoneal mass. The excised tumor was a round, encapsulated soft tissue mass measuring 7 cm with a tan-brown cut surface. Microscopy showed uniform, epithelioid cells with clear cytoplasm, focal melanin pigmentation and mild nuclear atypia, arranged in sheets and nests around capillary-sized vessels in a dense sclerotic stroma. Additionally, co-existing epithelioid granulomas were noted. On immunohistochemistry (IHC), tumor cells were diffusely positive for HMB45; focally for desmin and smooth muscle actin (SMA), while negative for EMA, CD10, S100-P, Melan A, CD34, AMACR and CK MNF116. This case reinforces sclerosing PEComa as an uncommon, but a distinct clinicopathological entity and exemplifies diagnostic challenge associated with it; necessitating application of IHC markers for its correct identification. Presence of melanin pigment and granulomatous inflammation in the present tumor constitute as novel histopathological findings in a sclerosing PEComa.

Clinicopathological spectrum of 19 adenosarcomas of female genital tract, including uncommon clinical associations and immunohistochemical profile, reviewed at a single institution.

Background: Adenosarcomas of the female genital tract have been rarely documented as case series from our continent. Materials and Methods: Over a seven-year period, 19 adenosarcomas were critically reviewed. Results: Nineteen tumors occurred in the age range of 21-65 years (mean: 43), in the endometrium (8), endometrium and cervix (4), cervix (4), and ovary (3). Four cases displayed coexisting leiomyomas; two, adenomyosis; two on background endometriosis; and one in post-treated cervix carcinoma. Histopathologically, the tumors were low grade (10; 52.6%) and high grade (9; 47.3%), the latter with sarcomatous overgrowth (SO) (7/9 cases). Dedifferentiation (8, 42.1%) and conspicuous decidualization (2) were noted. Immunohistochemically, the tumors focally expressed CD10 (4/6), smooth muscle actin (SMA) (3/8), desmin (8/11); diffuse vimentin (7/7), and estrogen receptor/progesterone receptor (ER/PR) (2/4). Ki-67 (6 cases) varied 5-20%. Seventeen patients underwent surgery and four received adjuvant treatment (3/4 high-grade tumors). Five tumors recurred (4 high-grade tumors with SO) and one metastasized. Among 11 patients, five were alive with disease (AWD) (mean: 29.4 months) and six, free of disease (FOD) (mean: 15 months), the latter mostly with low-grade type tumors (83.3% cases). Conclusions: Diverse clinicopathological spectrum was noted within adenosarcomas. Low-grade tumors were less aggressive than high-grade ones, with SO. Immunohistochemically, lower CD10 and ER/PR positivity was noted in high-grade tumors. Surgery formed the mainstay of treatment. Adjuvant treatment was offered in high-grade subtypes, including in tumors with SO.

Analysis of CD83 antigen expression in human breast fibroadenoma and adjacent tissue / Análise da expressão do antígeno CD83 no fibroadenoma mamário humano e no tecido adjacente

CONTEXT AND OBJECTIVE: Dendritic cell maturation is considered essential for starting an immune response. The CD83 antigen is an important marker of dendritic cell maturation. The objectives here were to analyze CD83 antigen expression in human breast fibroadenoma and breast tissue adjacent to the lesion and to identify clinical factors that might influence this expression. DESIGN AND SETTING: This was a retrospective study at a public university hospital, in which 29 histopathological samples of breast fibroadenoma and adjacent breast tissue, from 28 women of reproductive age, were analyzed. METHODS: The immunohistochemistry method was used to analyze the cell expression of the antigen. The antigen expression in the cells was evaluated by means of random manual counting using an optical microscope. RESULTS: Positive expression of the CD83 antigen in the epithelial cells of the fibroadenoma (365.52; standard deviation ± 133.13) in relation to the adjacent breast tissue cells (189.59; standard deviation ± 140.75) was statistically larger (P < 0.001). Several clinical features were analyzed, but only parity was shown to influence CD83 antigen expression in the adjacent breast tissue, such that positive expression was more evident in nulliparous women (P = 0.042). CONCLUSIONS: The expression of the CD83 antigen in the fibroadenoma was positive and greater than in the adjacent breast tissue. Positive expression of the antigen in the adjacent breast tissue was influenced by parity, and was significantly more evident in nulliparous women.

CONTEXTO E OBJETIVOS: A maturação da célula dendrítica é considerada essencial para o início da resposta imune. O antígeno CD83 é um importante marcador da maturação da célula dendrítica. Os objetivos são analisar a expressão do antígeno CD83 no fibroadenoma mamário humano e no tecido mamário adjacente à lesão e identificar fatores clínicos que possam influenciar esta expressão. TIPO DE ESTUDO E LOCAL: Este é um estudo retrospectivo, realizado em um hospital público universitário, onde 29 amostras histopatológicas de fibroadenomas de mamas e de tecidos mamários adjacentes, de 28 mulheres em idade reprodutiva, foram analisados. MÉTODOS: O método de imunoistoquímica foi utilizado na análise da expressão celular do antígeno. A expressão do antígeno nas células foi avaliada por contagem aleatória e manual utilizando-se microcópio de luz. RESULTADOS: A expressão positiva do antígeno CD83 nas células epiteliais dos fibroadenomas (365,52; desvio padrão ± 133,13) em relação às células do tecido mamário adjacente (189,59; desvio padrão ± 140,75) foi estatisticamente superior (P < 0,001). Vários aspectos clínicos foram analisados, porém, a paridade se mostrou influente na expressão do antígeno CD83 no tecido mamário adjacente, onde a expressão positiva foi mais evidente nas mulheres nulíparas (P = 0,042). CONCLUSÕES: A expressão do antígeno CD83 foi positiva e mais expressiva no fibroadenoma do que no tecido mamário adjacente. A expressão positiva do antígeno no tecido mamário adjacente foi influenciada pela paridade, sendo significativamente mais evidente nas mulheres nulíparas.

Composite epithelial kidney tumor comprising of adeno and neuroendocrine carcinomatous components: An unusual variant of renal cell carcinoma.

Renal cell carcinomas accounts for an approximately 2% of human malignancies with atleast ten different histological subtypes recognized by the World Health Organization (WHO) 2004 classification. Composite carcinomas with dual divergent epithelial differentiation in kidneys are extremely uncommon. We report an unusual case of a 37-year-old female who presented with symptoms related to renal tumor for the last three years. Computed tomography scan revealed a large heterogenously contrast enhancing left kidney mass comprising of two distinct histological components of low grade adenocarcinomatous and carcinoid-like low grade neuroendocrine carcinomas with presence of hilar lymph nodal metastases of both the components. The component of adenocarcinoma was immunoreactive to E-cadherin, cytokeratins 7 and 19 with negativity for cluster of differentiation 10, cytokeratin 20, CD117, and vimentin; while the neuroendocrine component was immunoreactive for vimentin, chromogranin and synaptophysin with negativity for CD10, CD117, and cytokeratins 7, 19 and 20. MIB-1 labeling index in the both the components was 2-3%. The present case is the first of its kind to be reported in the kidney and emphasizes the diversity potential of kidney tumors.

Avaliação dos valores sérico e pleural dos marcadores tumorais CEA, CYFRA21-1 e CA 15-3 em portadores de derrame pleural / Evaluation of serum and pleural levels of the tumor markers CEA, CYFRA21-1 and CA 15-3 in patients with pleural effusion

OBJETIVO: Dosar os marcadores tumorais antígeno carcinoembrionário (CEA), fragmento da citoqueratina 19 (CYFRA21-1) e antígeno glicosídico associado a tumor 15-3 (CA 15-3) em sangue e líquido pleural de portadores de derrames pleurais benignos e malignos, avaliando a sensibilidade de cada um deles nesses fluidos. MÉTODOS: Avaliamos prospectivamente 85 pacientes com derrame pleural. O estudo do líquido pleural obedeceu a critérios determinados pela literatura. A dosagem dos marcadores foi realizada por eletroquimioluminescência. A sensibilidade foi determinada sob a condição de que a especificidade fosse > 90 por cento. RESULTADOS: Foram diagnosticados 36 casos malignos (42,4 por cento), 30 benignos (35,3 por cento); em 19 pacientes (22,3 por cento), o diagnóstico foi inconclusivo. Nos casos malignos, os valores de CEA e CYFRA21-1 foram maiores no líquido pleural do que no sangue, fato não observado para o CA 15-3. Nos casos benignos, os valores do CYFRA21-1 foram maiores no líquido pleural do que no soro, enquanto que para o CEA e o CA 15-3, ocorreu o oposto. Todos os marcadores apresentaram diferença significativa entre os casos malignos e benignos, em líquido pleural e soro. Foi encontrada sensibilidade para CEA, CYFRA21-1 e CA 15-3 no líquido pleural de 69,4 por cento, 69,4 por cento e 66,7 por cento, respectivamente e quando associados, foi 80,6 por cento. No soro, a sensibilidade foi 57,1, 71,4 e 48,6 por cento para CEA, CYFRA21-1 e CA 15-3, respectivamente, e quando associados, foi 77 por cento. CONCLUSÃO: Os resultados sugerem que a utilização desses marcadores pode ser útil na diferenciação entre derrames pleurais malignos e benignos.

OBJECTIVE: To determine the levels of the tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and carbohydrate antigen 15-3 (CA 15-3) in the blood and pleural fluid of patients with benign or malignant pleural effusion, evaluating the sensitivity of each marker in these fluids. METHODS: We prospectively evaluated 85 patients with pleural effusion. The study of the pleural fluid observed the criteria established in the literature. Levels of the markers were determined using electrochemiluminescence. The sensitivity was determined on the condition that the specificity was > 90 percent. RESULTS: Of the 85 cases, 36 (42.4 percent) were malignant, 30 (35.3 percent) were benign, and the results were inconclusive in 19 (22.3 percent). In the malignant cases, the CEA and CYFRA21-1 levels were higher in the pleural fluid than in the blood, which was not observed for CA 15-3. In the benign cases, the CYFRA21-1 levels were higher in the pleural fluid than in the blood, whereas the opposite was found for CEA and CA 15-3. There were significant differences between malignant and benign cases for all markers, in pleural fluid and blood. In the pleural fluid, the sensitivity of CEA, CYFRA21-1 and CA 15-3 was 69.4, 69.4 and 66.7 percent, respectively, and the combined sensitivity was 80.6 percent. In the blood, the sensitivity was 57.1 percent, 71.4 percent and 48.6 percent for CEA, CYFRA21-1 and CA 15-3, respectively, and the combined sensitivity was 77 percent. CONCLUSION: The results suggest that these markers might be useful in the differentiation between malignant and benign pleural effusion.

Morphometric evaluation of NB84, synaptophysin and AgNOR is useful for the histological diagnosis and prognosis in peripheral neuroblastic tumors (pNTs)

OBJECTIVE: To study the importance of NB84, synaptophysin and AgNOR and explore the quantitative association of these factors with diagnosis and outcome as well as the association between NB84 and AgNOR and other tumor and stromal factors in twenty-eight peripheral neuroblastic tumors. METHODS: We assessed AgNORs, NB84, synaptophysin and several other markers in tumor tissues from 28 patients with primary neuroblastic tumors. The treatment included: surgery for stage 1, chemotherapy and bone marrow transplantation for most of stages 3 and 4. Histochemistry, immunohistochemistry and morphometry were used to evaluate the amount of tumor staining for AgNOR, NB84 and synaptophysin; the outcome for our study was survival time until death due to recurrent neuroblastic tumors. RESULTS: Only stage (p<0.01), AgNOR (p<0.01), NB84 (p<0.01) and synaptophysin (p=0.01) reached statistical significance as prognostic indicators. CONCLUSIONS: Determination of NB84 and synaptophysin are useful tools for the diagnosis of peripheral neuroblastic tumors The association of the evaluation of AgNOR expression by the tumor cells may provide an important contribution to the prognostic evaluation and management approach of the patients.

OBJETIVO: Estudar a importância dos marcadores NB84 e AgNOR e explorar as relações quantitativas entre esses marcadores com o diagnóstico e prognóstico assim como as relações entre NB84 e AgNOR e outros marcadores tumorais e estromais em 28 tumores neuroblásticos periféricos. MÉTODOS: Examinamos AgNOR, NB84 e sinaptofisina e vários outros marcadores em tecidos tumorais de vinte e oito pacientes com tumors neuroblásticos primários. Tratamento dos pacientes incluiu: cirurgia para o estágio 1, quimioterapia e transplante de medula óssea para a maioria dos pacientes nos estágios 3 e 4. Utilizamos histoquímica, imunohistoquímica e morfometria para avaliar a intensidade e extensão de expressão do AgNOR, NB84 e sinaptofisina, tendo o prognóstico dos pacientes incluído o tempo de sobrevida até a morte por recurrência dos tumores neuroblásticos. RESULTADOS: Estadiamento (p<0.01), AgNOR (p<0.01), NB84 (p<0.01) e sinaptofisina (p=0.01) foram marcadores independents de sobrevida. CONCLUSÕES: A determinação dos marcadores NB84 e sinaptofisina mostrou-se como uma ferramenta útil no diagnóstico dos tumors neuroblásticos periféricos; a associação desses marcadores à expressão de AgNOR pelas células tumorais contribuiu à determinação do prognóstico e estabelecimento do protocolo terapêutico para os pacientes.

Diagnóstico precoz de metástasis de melanoma mediante biopsia de linfonodo centinela: informe preliminar / Early diagnosis of melanoma metastasis by sentinel lymph node biopsy

Se presenta un estudio de linfonodo centinela y la experiencia inicial en el diagnóstico de micro metástasis linfática en melanoma maligno de piel, en un período de dos años. Se identificó en el pre operatorio el sitio del linfonodo centinela mediante albúmina marcada con Tc99 y, en el intra operatorio, con tinción vital con azul de isosulfán para seleccionar a los pacientes con micro metástasis que se pueden beneficiar con tratamiento quirúrgico linfático, descartar la cirugía ganglionar en los pacientes con linfonodo centinela negativo y reducir la morbilidad asociada al tratamiento quirúrgico. El criterio de inclusión incluyó pacientes con tumores Clark III o superior. Se incluyeron 6 pacientes; 2 Clark III, 3 Clark IV y un paciente Clark V. El diagnóstico de micro metástasis se realizó mediante tinción hematoxilina-eosina y estudio histoquímico de antígenos Melan A, S 100 y HMB 45. En dos pacientes Clark III y uno Clark IV, el estudio con H-E e inmunohistoquímica no identificó micro metástasis. Un paciente Clark IV no evidenció metástasis en el primer estudio con H-E; sin embargo, la inmunohistoquímica mostró micro metástasis con los tres marcadores tumorales. La revisión de las placas H-E confirmó el hallazgo. Un paciente con micro etapa IV y uno con micro etapa V mostraron metástasis a la tinción H_E y se confirmó la presencia de anticuerpos para los marcadores Melan A, S 100 y HMB 45. En este estudio el uso de Melan A, S 100 y HMB 45 mejoró la sensibilidad del diagnóstico histológico de metástasis linfáticas en un 20 por ciento y redujo a la mitad la indicación de disección ganglionar regional.

Marcadores morfológicos de prognóstico no mesotelioma maligno: um estudo de 58 casos / Morphological aspects as prognostic factors in malignant mesothelioma: a study of 58 cases

OBJETIVO: Diversos marcadores têm se mostrados promissórios como preditores do diagnóstico e prognóstico do mesotelioma maligno (MM). MÉTODO: Mediante estudo morfométrico e inmunomarcação de componentes estromais (calretinina, CEA, Leu-M1 e trombomodulina) e nucleares (p53 e Ki-67), avaliamos a sobrevida após o diagnóstico de 58 pacientes com tumores malignos de pleura. RESULTADOS: O padrão histológico típico do mesotelioma maligno foi encontrado em 50 casos e o padrão atípico em 8 casos. Imunohistoquimicamente foram confirmados 40 casos como sendo mesoteliomas, 11 como adenocarcimonas e 7 casos do padrão atípico não puderam ser classificados. A análise multivariavel do Cox demonstrou a coexistência de um maior fator de risco de morte (476.2), nos pacientes com idade avançada, subtipo histológico bifásico e componentes de expressão nuclear. CONCLUSÃO: A calretinina foi o marcador inmunohistoquímico (IHQ) mais útil para o diagnóstico do mesotelioma e o CEA para o de adenocarcinoma. A quantificação por IHQ da trombomodulina foi fundamental na diferenciação do mesotelioma quando este foi positivo tanto para calretinina e como para o CEA. A informação prognostica mais valiosa foi a fornecida pela análise rotineira histopatológica do tipo histológico tumoral. Um ponto importante, divisor natural, foi a idade com uma media de 55 anos e 30.5 por cento de componentes nucleares de marcação IHQ, separando os pacientes em dois grupos: pacientes com uma sobrevivência curta contra pacientes com uma sobrevivência mais longa que a esperada. Assim, a análise histopatológica oferece uma arma poderosa e de elevado potencial para guiar no tratamento adjuvante de quimioterápicos após a retirada cirúrgica do mesotelioma.

OBJECTIVE: Various markers have shown promise as diagnostic markers and prognostic predictors in malignant mesothelioma (MM). METHODS: Through morphometric and immunological studies of markers in stromal components (calretinin, CEA, Leu-M1 and thrombomodulin) and nuclear components (p53 and Ki-67), we evaluated post-diagnosis survival in 58 patients with MM. RESULTS: The histologic pattern of the MM was typical in 50 cases and atypical in 8. Through immunohistochemistry, we confirmed 40 cases of mesothelioma and 11 cases of adenocarcinoma, although we were unable to classify 7 of the 8 cases presenting atypical histologic patterns. Cox multivariate analysis revealed that the risk factor for death was higher (476.2) among patients of advanced age, presenting the biphasic subtype and testing positive for components expressed at the nuclear level. CONCLUSION: The most useful immunohistochemical markers were was calretinin (for mesothelioma) and CEA (for adenocarcinoma). Immunohistochemical quantification of thrombomodulin facilitated the diagnosis of mesothelioma in patients testing positive for both calretinin and CEA. The most useful prognostic information was that provided by the routine histopathological analysis of the tumor type. It is of note that the combination of a mean age of 55 years and 30.5 percent immunohistochemical markers in nuclear components created a natural dividing point between patients in which survival was shorter than expected and those in which it was longer than expected. Therefore, histopathological analysis offers a powerful weapon with great potential to inform decisions regarding the use of adjuvant chemotherapy after surgical excision of a mesothelioma.

Prevalence of SIL and SCCA in human immunodeficiency virus-seropositive women at anonymous clinic in Chonburi Hospital.

The series of 231 HIV-infected women were recruited in Chonburi Hospital, Thailand. Demographic, gynecologic factors were interviewed Pap smear was performed and classified based on the Bethasda system (1991) by a cytotechnologist. All abnormal Pap smear slides were reviewed by a cytopathologist. The prevalence of LSIL, HSIL and SCCA were 2.2%, 8.3% and 2.2%, respectively. There was statistically significant association between the duration of HIV infection and occurrence of SIL and SCCA. (p = 0.007) CONCLUSION: The present study showed a high prevalence of SIL and SCCA in-HIV-infected women at Chonburi Hospital.

Componente oligodendroglial e neuronal em glioblastomas: possível relação com o prognóstico / Oligodendroglial and neuronal component in glioblastomas: possible relation with prognosis

Glioblastomas são tumores astrocíticos de alto grau de malignidade e o diagnóstico baseado nos critérios histológicos atuais não tem explicado a maior sobrevida observada em alguns casos. A presença de um componente oligodendroglial foi proposta mais recentemente como um possível indicador de maior sobrevida, tanto pela OMS quanto pela classificação de Sainte Anne 2000. Esta última propõe ainda que um componente neuronal está relacionado com maior sobrevida. O objetivo deste estudo foi rever tumores de 40 pacientes diagnosticados como glioblastomas pelos critérios da OMS, com o propósito de identificar: a presença de um componente oligodendroglial utilizando critérios morfológicos; a presença de um componente neuronal utilizando marcadores imuno-histoquímicos (anticorpos anti-neurofilamento e sinaptofisina). Objetivou-se também correlacionar os achados histológicos e imuno-histoquímicos com a sobrevida dos pacientes, estudando também outras variáveis que podem ter influência na sobrevida. Foram identificados 11 tumores com componente oligodendroglial e 7 com componente neuronal. Apesar do pequeno número de casos estudados, a presença de um componente oligodendroglial associou-se com maior sobrevida. O valor da expressão de marcadores neuronais em gliomas malignos precisa ser confirmado com a avaliação de séries maiores.

Changing patterns and re-distribution of antigen in poorly differentiated carcinomas: its implications in tumour diagnosis.

The variability of expression of tumour-associated antigens via either antigenic heterogeneity or antigenic modulation presents a basic problem in immunohistochemical diagnosis of poorly/undifferentiated tumours. This work was designed to study antigenic expression on human resected epithelial tumours by a panel of most widely used antibodies (EMA, CEA, AUAI & Cytokeratin) in relation to tumour differentiation and polarization. It was observed that poorly differentiated carcinoma with loss of polarity show homogeneous membrane staining (with antibodies against EMA, CEA & AUAI) in contrast to either apical (luminal) or basolateral membrane staining in well differentiated counterparts. Biochemical studies have shown that apical and basolateral epithelial cell membrane domains have a characteristic set of glycoproteins. Tight junctions are essential for maintaining this functional polarization. It was concluded that structural and functional abnormalities of tight junctions in poorly differentiated carcinomas results in loss of polarity with progressive invasion of the cell surface by antigenic glycoprotein and resultant homogeneous individual cell antigenic expression in poorly differentiated carcinomas. This study demonstrates that antigenic expression on tumour cells is not static, but dynamic and heterogeneity of antigenic expression may well be due to biological factors such as spatial configuration of the lesion.

Expresión de antígenos en órganos normales y tumorales / Expretion of antigens organs normality and tumors

Las técnicas modernas en el campo inmunológico y de biología molecular han significado una revolución en el campo biomédico al permitir la detección, reconocimiento y manipulación biológica de antígenos presentes en órganos, tejidos y células especializadas. Se discute la importancia médica de la expresión de diversos antígenos que incluyen marcadores de superficie, productos solubles, citoquinas e isoenzimas con énfasis en la comparación de marcadores con la expresión antigénica de tejidos normales a nivel embrionario y postnatal

Estudio inmunohistoquimico de BCL-2 y MIB-1/KI-67 en el carcinoma de mama: analisis retrospectivo en 238 casos / Immunohistochemical detection of bcl-2 and MIB-1/Ki-67 in breast cancer: retrospective analysis of 238 cases

Es de interés conocer si un indicador de proliferación como el anticuerpo MIBl contra el antígeno Ki-67 y la expresión de bcl-2, proteína relacionada con el bloqueo de la apoptosis, tienen relación entre sí y con potenciales factores pronósticos del câncer de mama. Para ello en este trabajo se estudian retrospectivamente 238 casos de carcinoma de mama en estadíos I y II con un seguimiento mínimo de 5 años. Los resultados muestran que la alta expresión de MIB-1 se asoció con grados nuclear e histológico altos (p < O,001 para ambos), con receptores de estrógenos y de progesterona negativos (p = O,009 y p = O,004 para cada uno respectivamente) y con población menor de 60 anos (p = O,014). La alta expresión de bcl-2 se relacionó con tumores más pequeños (p = O,001); receptores de estrógenos y de progesterona positivos (p < O,001 para ambos), grado nuclear bajo (p < O,001), grado histológico bajo (O,002), estadío I (p = O,01) y baja expresión de MIB-1 (p = O,025). La regresión univariada de Cox demostró una significativa asociación de la alta expresión de MIB-1 y de la baja expresión de bcl2 con menor sobrevida global (p = O,002 y p = O,04 para cada uno respectivamente). Por otra parte el anáiisis multivariado de selección por pasos de Cox mostró que la expresión de MIB-1 fue un factor pronóstico independiente.