Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas.

OBJECTIVE: Soft tissue sarcomas (STSs) are heterogeneous tumors displaying multiple and complex molecular abnormalities with no specific pattern. Despite current therapeutic advances, the patients with STS still have a poor outcome, which makes it necessary to find out new prognostic markers. The Raf kinase inhibitory protein (RKIP) has been associated with prognosis in several human neoplasms; however, its role in STS is unknown. METHODS: In the present study RKIP expression was assessed by immunohistochemistry in a series of 87 STSs, and its expression profile was associated with the patients' pathological parameters. RESULTS: We found that RKIP is expressed in the cytoplasm of the great majority of cases, and absent in only approximately 18% of cases (16/87). Importantly, we observed that loss of RKIP expression was associated with poor outcome, constituting an independent prognostic marker. CONCLUSION: This is the first study assessing RKIP expression levels in STS. We showed that loss of RKIP expression is present in a small subset of cases; however, its absence was associated with poor survival and may be a potential marker for STS prognosis.

Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization.

BACKGROUND: Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs). METHODS: Immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients' clinical-pathological parameters. RESULTS: MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival. CONCLUSIONS: The present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients' prognosis, while nuclear expression is associated with better prognosis.

Immunoexpression of Ezrin and CD44 in patients with osteosarcoma.

BACKGROUND: Metastasis is an important prognostic factor among patients with osteosarcoma. It has been reported that ezrin is important in enabling metastasis and that CD44 expression leads to functional increases in ezrin activation. OBJECTIVE: The aim of this study was to correlate ezrin and CD44 expression with prognosis. SAMPLES AND METHODS: Patients with a diagnosis of osteosarcoma who had been treated at Hospital de Cancer de Barretos, Barretos, SP, Brazil, between 2000 and 2005 were selected from the Hospital Tumor Registry. Fifty-two patients and, among these, 34 surgical biopsy specimens of osteosarcoma before chemotherapy were reviewed by the Pathology Department. Ezrin and CD44H protein expression was evaluated using immunohistochemistry on the initial biopsy for these 34 samples. RESULTS: Most patients (76%) were ezrin-positive in cytoplasm and membrane (38.2%); 58.9% presented high-intensity staining and 50.0% had high scores. Half of the patients were CD44H-positive, predominantly in cytoplasm (38.2%); 20.6% presented staining in more than 50% of the cells. None of the markers showed associations with any of the clinicopathologic variables studied. Among the ezrin-positive patients, the 5-year survival rate was 12.8%, whereas it was 41.7% among ezrin-negative patients (P=0.121). The interaction between ezrin and poor histologic response among nonmetastatic patients showed an association with relapse-free 5-year survival of 100% versus 12.7% (P=0.042). The overall survival rates for CD44-positive and negative patients were similar (21.5% and 25.3%, respectively) (P=0.676). CONCLUSIONS: Neither CD44H nor ezrin immunoexpression could predict the prognosis for patients with osteosarcoma in our small sample.

Metalloproteinases and colorectal cancer. Correlation of gene expression and clinical-pathological parameters.

PURPOSE: To analyze gene and protein expression of metalloproteinases 1, 2, 9, 11 and 16 and their correlation with clinicopathological variables in colorectal adenocarcinoma. METHODS: A retrospective study of 114 patients with colorectal adenocarcinoma treated surgically in the period 2006 to 2008 in Hospital de Câncer de Barretos - Fundação Pio XII. The evaluation of gene expression was performed by RT-PCR, and protein by immunohistochemistry. The analysis of gene expression was classified as overexpressed genes and poorly expressed (fold change of approximately 2, p<0.05). The positivity of the markers in the immunohistochemical study was performed by semi-quantitative analysis. The tissue of TMA (Tissue Microarray) was done by two independent pathologists. RESULTS: The gene expression validated by immuno - histochemical was MMP-1(p= 0.00 and 1.57 fold change) and MMP - 2 (p= 0.01 and - 1.84 to fold change) when correlated with the histological types mucinous and adenocarcinoma NOS, MMP9 (p=0.01 and fold change of 1.13) and MMP-16 (p=0.03 and 1.61 fold change) when compared with the histological types villous and adenocarcinoma NOS, MMP - 11 statistically significant in relation to male (p = 0.04 and 1.65 fold change). CONCLUSIONS: The MMPs 1, 2, 9, 11 and 16 gene and protein expression with statistical significance in at least one of the clinicopathological variables studied. Thus, we conclude that these MMPs have potential as a prognostic factor in colorectal adenocarcinoma.

Immunohistochemical expression of vegf and her-2 proteins in osteosarcoma biopsies.

OBJECTIVES: To identify the prevalence of erbB-2 and vascular endothelial growth factor (VEGF) in osteosarcoma biopsies and to correlate them with possible prognosis factors. METHODS: Retrospective study conducted at the Hospital do Câncer de Barretos-SP including 27 osteosarcoma biopsies immunohistochemically stained for VEGF and erbB-2. The pathological characteristics were collected from medical records of patients to correlate with markers. RESULTS: In 27 biopsies, four overexpressed VEGF and three overexpressed erbB-2. Two thirds of patients had no metastases. Almost all patients with overexpression of VEGF showed metastases. Overexpression of erbB-2 was inversely related to the presence of metastases. There was no significant association between markers and prognosis. CONCLUSION: We identified a low prevalence of erbB-2 and VEGF in the sample. There was no significant association between overexpression of markers and pathological features. A larger sample and a longer follow-up, in addition to using new laboratory techniques can determine the real expression of VEGF and erbB-2 and its role in osteosarcoma . Level of Evidence III, Case-Control Study.

Carotid artery rupture following radioiodine therapy for differentiated thyroid carcinoma.

INTRODUCTION: Radioiodine therapy for patients with differentiated thyroid cancer aims at reducing tumor recurrence by eradicating residual macro- and microscopic foci. Side effects are generally rare, tenuous and transient, with little clinical significance. OBJECTIVE: To report a rare case of differentiated thyroid carcinoma presenting a large expansive solid mass at the base of the skull, with invasion of the left masticatory muscle and adjacent subcutaneous tissue, and without invasion of the carotid space, which evolved to carotid artery rupture following radioiodine therapy. DISCUSSION: Side effects are uncommon after radioiodine therapy and when present, have mild intensity. Serious adverse events are very rare, especially those arising from structures not directly invaded by metastatic tissue with radioiodine uptake, as occurred in this case. This occurrence serves to raise awareness of the need for increased care when using radioiodine therapy on high-avidity masses located close to important structures.

Mucopolysaccharidosis type II: skeletal-muscle system involvement.

Mucopolysaccharidosis type II (MPS-II) is a rare lysosomal storage disorder caused by deficiency in the activity of the enzyme iduronate-2-sulphatase. This enzyme is responsible for the catabolism of two different glycosaminoglycans (GAGs), dermatan sulfate and heparan sulfate. Lysosomal accumulation of these GAG molecules results in cell, tissue, and organ dysfunction. The skeletal-muscle system involvement is because of essential accumulated GAGs in joints and connective tissue. MPS-II has many clinical features and includes two recognized clinical entities, mild and severe, that represent two ends of a wide spectrum of clinical severity. The aim of this study is to review the involvement of the skeletal-muscle system in MPS-II.

Expressão imuno-histoquímica das proteínas VEGF e HER-2 em biópsias de osteossarcoma / Immunohistochemical expression of VEGF and HER-2 proteins in osteosarcoma biopsies

Objetivos: Identificar a prevalência de HER-2 e do fator de crescimento do endotélio vascular (VEGF) em biópsias de osteossarcoma e correlacioná-los com possíveis fatores de prognóstico. Métodos: estudo retrospectivo realizado no Hospital de Câncer de Barretos-SP incluindo 27 biópsias de osteossarcoma imuno-histoquimicamente coradas para VEGF e HER-2. Características clínico-patológicas foram coletadas dos prontuários médicos dos pacientes para correlação com marcadores. Resultados: em 27 biópsias, quatro foram superexpressas para VEGF e três para HER-2. Dois terços dos pacientes eram não metastáticos. Quase todos pacientes com VEGF superexpresso apresentaram metástases. A superexpressão para HER-2 apresentou relação inversa à presença de metástases. Não houve associação significativa entre os marcadores e o prognóstico. Conclusão: identificamos baixa prevalência de VEGF e HER-2 na amostra. Não houve associação significativa entre superexpressão dos marcadores e características clínico-patológicas. A ampliação da amostra e do tempo de seguimento, além do emprego de novas técnicas laboratoriais pode determinar a real expressão de VEGF e HER-2 e seu papel em osteossarcomas. Nível de Evidência III, Estudo de Caso-controle.

Objectives: To identify the prevalence of erbB-2 and vascular endothelial growth factor (VEGF) in osteosarcoma biopsies and to correlate them with possible prognosis factors. Methods: retrospective study conducted at the Hospital do Câncer de Barretos-SP including 27 osteosarcoma biopsies immunohistochemically stained for VEGF and erbB-2. The pathological characteristics were collected from medical records of patients to correlate with markers. Results: In 27 biopsies, four overexpressed VEGF and three overexpressed erbB-2. Two thirds of patients had no metastases. Almost all patients with overexpression of VEGF showed metastases. Overexpression of erbB-2 was inversely related to the presence of metastases. There was no significant association between markers and prognosis. Conclusion: We identified a low prevalence of erbB-2 and VEGF in the sample. There was no significant association between overexpression of markers and pathological features. A larger sample and a longer follow-up, in addition to using new laboratory techniques can determine the real expression of VEGF and erbB-2 and its role in osteosarcoma. Level of Evidence III, Case-Control Study.

Carotid artery rupture following radioiodine therapy for differentiated thyroid carcinoma / Ruptura de carótida pós-iodoterapia em carcinoma diferenciado de tireoide

INTRODUCTION: Radioiodine therapy for patients with differentiated thyroid cancer aims at reducing tumor recurrence by eradicating residual macro- and microscopic foci. Side effects are generally rare, tenuous and transient, with little clinical significance. OBJECTIVE: To report a rare case of differentiated thyroid carcinoma presenting a large expansive solid mass at the base of the skull, with invasion of the left masticatory muscle and adjacent subcutaneous tissue, and without invasion of the carotid space, which evolved to carotid artery rupture following radioiodine therapy. DISCUSSION: Side effects are uncommon after radioiodine therapy and when present, have mild intensity. Serious adverse events are very rare, especially those arising from structures not directly invaded by metastatic tissue with radioiodine uptake, as occurred in this case. This occurrence serves to raise awareness of the need for increased care when using radioiodine therapy on high-avidity masses located close to important structures.

INTRODUÇÃO: Iodoterapia em pacientes com carcinoma diferenciado da tireoide tem o objetivo de reduzir a recorrência tumoral erradicando focos residuais macro e microscópicos. Os efeitos colaterais, em geral, são raros, tênues e transitórios, com pouca repercussão clínica. OBJETIVO: Relatar um caso raro de carcinoma diferenciado da tireoide apresentando grande massa sólida expansiva na base do crânio, com invasão da musculatura mastigatória esquerda e do tecido subcutâneo adjacente, sem invasão do espaço carotídeo que evoluiu com ruptura de carótida pós-iodoterapia. DISCUSSÃO: Os efeitos colaterais pós-iodoterapia são pouco frequentes e, quando presentes, de intensidade discreta. Os eventos adversos graves são muito raros, em especial, aqueles decorrentes de estruturas não invadidas diretamente pelo tecido metastático iodocaptante, como nesse caso, alertando também para a necessidade do aumento dos cuidados na terapia de grandes massas ávidas pelo radioiodo próximas às estruturas nobres.

Chondrosarcoma secondary to hereditary multiple exostosis treated by extended internal hemiplevectomy

The authors report on the case of a 28-year-old patient with extensive chondrosarcoma of the left ischium and pubis involving hip joint, skin, and soft tissue of the gluteal region, secondary to hereditary multiple exostosis submitted to an extended internal. Enneking type II and III hemipelvectomy. No prosthesis or arthrodesis was used. A few years ago, patients with extensive tumors like this one were treated with interilioabdominal amputation, resulting in a loss of quality of life. Two years after the limb-preserving surgery, this patient was disease free, with good functional results, including bipedal ambulation with support.

Diagnóstico do exame por congelação em patologia cirúrgica: análise de 1532 casos / Evaluation frozen section analysis in surgical pathology: a survey of 1532 cases

Foram avaliados 1532 casos de espécimes submetidos a exame por congelação durante ato cirúrgico, no ato de 1989, realizados pelo Departamento de Anatomia Patológica do Hospital A. C. Camargo da Fundação Antonio Prudente. Os diagnósticos dos exames por congelação foram comparados com os encontrados pelo exame de parafina e revelaram índices de especificidade de 98,3 porcento, sensibilidade de 96,5 porcento, e eficiência de 97,4 porcento valor preditivo positivo de 98 porcento e valor preditivo negativo de 96,9 porcento, que são semelhantes aos encontrados na literatura.

Computed tomography-guided fine-needle aspiration biopsy

The therapeutic and prognostic evaluation of malignant neoplasias depends largely upon a precise morphologic diagnosis. Several papers have focused on the importance of fine-needle aspiration under computed tomography guidance in the diagnosis of unresectable neoplasms and in the investigation of metastases. The objective of this study is to evaluate the diagnostic accuracy, the sensitivity, and the negative predictive value obtained with the technique. Fine-needle aspiration cytology (FNAC) was performed on 207 patients, with a total of 210 cases, from 1991 to 1994, under computed tomography (CT) guidance. There were 128 (61.8 percent) males and 79 (38.2 percent) females with a mean age of 41 years (range 1 to 91 years). Lung and liver were the most frequent anatomic sites. The analysis of this material disclosed 41 cases with cytological diagnosis of negative for malignancy (19.52 percent), and in 131 (62.38 percent), the diagnosis was positive. It was possible to define the cytologic lineage in 54 percent of the cases. The diagnosis in 14 (6.67 percent) cases was suspicious for malignancy, and in 24 (11.43 percent) cases the material was insufficient for the cytologic diagnossis. Of the 210 cases, 106 showed histological diagnosis and/or clinical follow-up. Forty-seven (44.3 percent) had histological diagnosis before the FNAC and 50 cases (56.7 percent) histological diagnosis after the procedure. The comparison between cytological and histological diagnosis showed a sensibility of 80.4 percent, specificity of 100 percent, positive predictive value of 100 percent and negative of 16.7 percent. The efficiency of the test was 81.1 percent. This study showed that FNAC, under computed tomography guidance, is a sensitive and specific technique for the diagnosis of deep-seated lesions.

Carcinoma epidermoide de mama / Squamous cell carcinoma of the breast

Foram investigados cinco casos de carcinoma espinocelular (CEC) da mama e um tumor raro, e foram descritos menos de 150 casos na literatura médica. Foram analisadas as características clínicas, anatomopatológicas e terapêuticas das pacientes portadoras de CEC da mama, atendidas no Hospital de Câncer de Barretos. Quatro pacientes chegaram ao hospital com tumores volumosos e localmente avançados (pT4b), sendo submetidas a mastectomia e esvaziamento axilar, e, ao contrário da literatura, todas apresentavam metástase axilar. A radioterapia foi realizada em todas as pacientes, e a quimioterapia com antracíclicos foi realizada em três pacientes. Os receptores de estrogênio, progesterona e c-erb B2 foram negativos. Todas as pacientes encontram-se vivas e sem doença em um período de seguimento mediano de 55,6 meses; fato superior ao observado para o carcinoma ductal. Esses casos vêm a contribuir para melhor conhecimento da biologia desse raro tumor.

The authors report five cases of breast squamous cell carcinoma, a very rare tumor, whose there were described lower than 150 cases in medical literature. We analyze the clinical, pathologic and therapeutic aspects of breast squamous cell carcinoma. Pour patients had large and locally advanced tumors (PT4b), and they were submitted to mastectomy and axillary dissection; whose were noted axillary metastases, uncommon fact. Radiotherapy was done in all patients, and three patients received antraciclic chemotherapy. The receptors of estrogen, progesterone and c-erb B2 were negative. The patients are live without disease in a median period of 55,6 months which is superior to invasive ductal carcinoma. This report of a case represents a contribution to better knowledge of biology of this rare tumor.

Carcinoma epidermóide de mama / Squamous cell carcinoma of the breast

Os autores analisaram quatro casos de carcinoma espinocelular da mama, um tumor raro, no qual foram descritos menos de cem casos na literatura médica. Analisaram-se as características clínicas, anatomopatológicas, terapêuticas das pacientes portadoras de carcinoma espinocelular da mama atendidas no Hospital de Câncer de Barretos. Todas as pacientes chegaram ao hospital com tumores volumosos e localmente avançados (pT4b). Os receptores de estrogênio, progesterona e c-erb B2 foram negativos. Todas as pacientes se submeteram a mastectomia e esvaziamento axilar e, ao contrário do que diz a literatura, todas apresentavam metástase axilar. Radioterapia foi realizada em todas as pacientes e quimioterapia com antracíclicos foi realizada em três pacientes. As pacientes encontram-se vivas e sem doença num período de seguimento mediano de 14,8 meses. Esses casos vêm a contribuir para melhor conhecimento da biologia desse raro tumor.

The authors report four cases of breast squamous cell carcinoma, a very rare tumor, whose with less than one hundred cases in described medical literature. We analyse the clinical, pathologic and therapeutic aspects of breast squamous cell carcinoma. All four patients had large e locally advanced tumors (pT4b). The receptors of estrogen, progesterone and c-erb B2 were negative. All patients were submitted to mastectomy and axillary dissection; whose were noted axillary metastases, uncommon fact. Radiotherapy was done in all patients, and three patients received antraciclic chemotherapy. The patients are alive without disease in a median period of 14,8 months. These cases represent a contribution to better knowledge of the biology of this rare tumor.

Punção aspirativa de fígado dirigida por tomografia computadorizada / Liver CT-guided aspirative biopsies

No período de 1992 a 1995, foram realizadas 68 punções aspirativas de nódulos hepáticos guiadas por tomografia computadorizada, no Hospital A. C. Camargo, São Paulo. Esses casos foram assim distribuidos: 44 casos (64,7 por cento) com diagnóstico de positivo para células neoplásticas, 6 casos (8,8 por cento) com diagnóstico negativo e 14 casos (20,5 por cento) de material insuficiente. Dos casos positivos (neoplasmas primárias e metástases), em 39 foi possível a deteminação da linhagem citológica. Houve 36 casos de carcinoma (7 de hepatocarcinoma, 18 adenocarcinoma, 1 carcinoma de pequenas células e 10 carcinomas sem outra especificação - SOE), 2 casos de melanoma e 1 caso de sarcoma. A correlação com os exames histopatológicos revelou não haver falso-positivos e alta concordância entre os diagnósticos citológicos e anatomopatológicos. Os resultados demonstram que a punção aspirativa de nódulos hepáticos guiada por tomografia computadorizada permite diagnóstico rápido de lesões neoplásticas, principalmente na avaliação de metástases.

Melanoma maligno: achados histopatológicos em olhos enucleados pós-braquiterpia com cobalto-90 / Malignant melanoma: histopathological findings in enucleated eyes after coblat-60 plaque therapy

Os autores avaliam os achados histopatológicos de 13 olhos com melanoma uveal submetidos à braquiterapia e posteriormente enucleados por insucesso com o tratamento ou por complicaçöes como hemorragia vítrea, descolamento total da retina e glaucoma neovascular. Os achados säo comparados com os de 13 olhos com emlanoma uveal, de dimensöes equivalentes, enucleados no mesmo período, sem qualquer tratamento prévio. Foram avaliados: o tipo histológico, pigmentaçäo, ruptura da membrana de Bruch, infiltraçäo linfocitária, fibrose, necrose, alteraçöes vasculares, infiltraçäo de esclera, assim como dos vasos episclerais e número de mitoses em 10 campos de aumento. Fibrose ocorreu somente no grupo irradiado. Houve predomínio da necrose difusa no grupo