Absence of TERT promoter mutations in colorectal precursor lesions and cancer

Abstract Hotspot mutations (c.-124bp G > A and c.-146bp G > A) in the promoter region of the TERT gene have been recently described in several types of solid tumors, including glioma, bladder, thyroid, liver and skin neoplasms. However, knowledge with respect to colorectal precursor lesions and cancer is scarce. In the present study we aimed to determine the frequency of hotspot TERT promoter mutations in 145 Brazilian patients, including 103 subjects with precursor lesions and 42 with colorectal carcinomas, and we associated the presence of such mutations with the patients clinical-pathological features. The mutation analysis was conclusive in 123 cases, and none of the precursor and colorectal carcinoma cases showed TERT promoter mutations. We conclude that TERT mutations are not a driving factor in colorectal carcinogenesis.

Expression of tumor suppressors miR-195 and let-7a as potential biomarkers of invasive breast cancer

OBJECTIVE: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. Some miRNAs, including let-7a and miR-195, have been described as tumor suppressors. However, the roles of these microRNAs in breast cancer progression remain controversial. The aim of this study is to evaluate miR-195 and let-7a expression as potential biomarkers of invasive breast cancer. METHODS: In the present study, 200 individuals were separated into three groups: (i) 72 women constituting the control group who were selected according to rigorous and well-established criteria; (ii) 56 patients with benign breast tumors; and (iii) 72 patients with malignant breast cancers of different clinical stages. The miR-195 and let-7a expression levels in serum were evaluated by real-time PCR. The results were assessed alone and in combination, and the analysis included an estimation of sensitivity and specificity in ROC curves. RESULTS: Compared with the benign and control groups, both microRNAs were downregulated in the malignant breast cancer patient group. Compared with the malignant group, the combination of both biomarkers in the control and benign groups showed good sensitivity and specificity in the serum with AUCs of 0.75 and 0.72, respectively. The biomarker combination for the control group versus the malignant group exhibited a better sensitivity and specificity than for the benign group versus the malignant group. CONCLUSION: These findings support the evidence that the analysis of miR-195 and let-7a can be used as a non-invasive biomarker for breast cancer detection.

Characterization, survival analysis, and expression of IGFR in tumor samples from patients diagnosed with Ewing family tumors treated at the Barretos Cancer Hospital / Caracterização, análise de sobrevida e expressão de IGFR nas amostras tumorais dos pacientes com diagnóstico dos tumores da família Ewing tratados no Hospital de Câncer de Barretos

ABSTRACT OBJECTIVES: Study the clinical characteristics of patients diagnosed with Ewing family tumors (EFTs) and survival analysis based on risk criteria and expression of the surface protein known as insulin-like growth factor (IGFR). METHODS: This was a retrospective cohort study based on clinical data from 77 patients diagnosed with EFTs treated by the Department of Pediatric Oncology at the Barretos Cancer Hospital in a period between 2003 and 2012. Biological samples of patients were examined for the presence of the surface receptor IGFR. RESULTS: The overall survival rate (OSR) of patients included in the study was 45% at five years, and EFS was 30% at five years. Metastasis at diagnosis was present in 44.2% of the sample; 88.2% of the sample was male (p < 0.001). The evaluation of the expression of IGFR in biological samples of patients was associated with the variable metastasis at diagnosis (p < 0.001). Worse prognosis was observed in patients with extrapulmonary metastasis (p = 0.009). The local treatment of neoplasia presented better prognosis in patients undergoing local surgical treatment (p < 0.001). CONCLUSIONS: These results showed a higher incidence of metastasis at diagnosis in patients with EFTs treated at the Barretos Cancer Hospital (BCH). Extrapulmonary metastases were a negative prognostic factor in this study. Surgical treatment of the primary tumor was a factor for better prognosis. Strong expression of IGFR was more frequent in patients with metastases at diagnosis, but did not represent a prognostic factor for EFTs.

RESUMO OBJETIVO: Estudar as características clínicas dos pacientes com diagnóstico de tumores da família Ewing (TFEs) e analisar a sobrevida baseada em critérios de risco e expressão da proteína de superfície conhecida como fator de crescimento semelhante à insulina (IGFR). MÉTODOS: Estudo de coorte retrospectivo, com base em dados clínicos de 77 pacientes com diagnóstico de TFEs tratados pelo Departamento de Oncologia Pediátrica do Hospital de Câncer de Barretos entre 2003 e 2012. Amostras biológicas de pacientes foram examinadas quanto à presença do receptor de superfície IGFR. RESULTADOS: Em cinco anos, a taxa de sobrevida global (SG) dos pacientes incluídos no estudo foi de 45% e a taxa de sobrevida livre de eventos (SLE) foi de 30%. Metástases no momento do diagnóstico foram observadas em 44,2% da amostra, sendo que desses, 88,2% eram do sexo masculino (p < 0,001). A avaliação da expressão de IGFR nas amostras biológicas dos pacientes apresentou associação com a variável metástase ao diagnóstico (p < 0,001). Pacientes com metástase extrapulmonar apresentaram pior prognóstico (p = 0,009). A modalidade de tratamento local da neoplasia apresentou melhor prognóstico em pacientes submetidos ao tratamento cirúrgico local (p < 0,001). CONCLUSÃO: Os resultados evidenciaram uma maior incidência de metástase ao diagnóstico nos pacientes com diagnóstico de TFEs tratados no Hospital de Câncer de Barretos. A metástase de localização extrapulmonar foi fator de pior prognóstico no estudo. O tratamento cirúrgico do tumor primário foi fator de melhor prognóstico. A expressão forte de IGFR esteve mais presente nos pacientes com metástase ao diagnóstico, porém não se mostrou como fator prognóstico nos TFEs.

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

Amiloidose primária mamária / Primary breast amiloidosis

A amiloidose mamária pode ser primária ou parte de uma doença sistêmica. O tumor amilóide primário representa 12,8% dos casos de amiloidose, sendo que a amiloidose primária da mama corresponde a 0,5% dos casos de amiloidose, representando entidade extremamente rara. Pode apresentar se como uma massa mamária, ser assintomático sob a forma de assimetria ou micro calcificações. Pode mimetizar lesão maligna e em alguns encontra se associada a um carcinoma concomitante. O tratamento da amiloidose primária da mama é a remoção cirúrgica da área suspeita, fato que encontra se associado a boa evolução. Descreve se um caso de amiloidose ma mária primaria, discutindo se os múltiplos fatores relacionados ao seu diagnóstico, diagnóstico diferencial, tratamento e seguimento.

Breast amyloidosis can be primary or part of a systemic disease. The primary tumor amyloid represents 12.8% of the cases of amyloidosis, and the primary breast amyloidosis corresponds to 0.5% of the cases of amyloidosis, representing a very rare entity. It may present as a breast mass or asymptomatic in the form of asymmetry or microcalcifications. It can also mimicking malignancy and in some cases it is associated with a concomitant carcinoma. The treatment of primary amyloidosis of the breast is the surgical removal of the suspected area, a fact that is associated with good outcome. We describe a case of primary breast amyloidosis, discussing the multiple factors related to the diagnosis, differential diagnosis, management and follow up.

Analysis of natural history of the diaphragmatic injury on the right in mice / Análise da evolução natural dos ferimentos diafragmáticos à direita em ratos

Objective: to evaluate natural evolution of right diaphragmatic injury after the surgical removal of a portion from hemi diaphragm. Methods: the animals were submitted to a surgical removal of portion from right hemi diaphragm by median laparotomy. The sample consists of 42 animals being 2 animals from pilot project and 40 operated animals. And the variables of the study were herniation, liver protection, healing, persistent diaphragm injury, evaluation of 16 channels tomography and the variables "heart rate" and "weight". Results: we analyzed 40 mice, we had two post-operative deaths; we had 17 animals in this group suffered from herniation (42.5%) and 23 animals didn't suffer from herniation (57.5%). Analyzing the tomography as image method in the evaluation of diaphragmatic hernia, we had as a method with good sensitivity (78.6%), good specificity (90.9%), and good accuracy (86.1%) when compared to necropsy. Conclusion: there was a predominance of healing of right hemi diaphragm, the size of initial injury didn't have influence on occurrence of the liver protection or hernia in mice.

Objetivo: avaliar a evolução natural do ferimento diafragmático à direita após a retirada cirúrgica de uma porção do hemidiafragma. Métodos: os animais foram submetidos à ressecção de uma porção do hemidiafragma à direita através da laparotomia mediana. Foram operados 40 ratos. As variáveis analisadas foram: herniação, proteção hepática, cicatrização, lesão persistente do diafragma, avaliação da tomografia computadorizada, frequência cardíaca e peso. Resultados: foram analisados 40 ratos. Houve duas mortes no pós-operatório. Dezessete animais tiveram herniação (42,5%) e 23 (57,5%), não. Analisando emprego da tomografia computadorizada na avaliação da hérnia diafragmática, tivemos um método com boa sensibilidade (78,6%), boa especificidade (90,9%) e boa acurácia (86,1%) quando comparados com a necrópsia. Conclusão: houve predomínio de cicatrização do hemidiafragma à direita e o tamanho da lesão inicial não influenciou na ocorrência de proteção hepática ou hérnia em ratos.

Pesquisa do linfonodo sentinela em carcinomas espinocelulares de cavidade oral classificados como T1 e T2 N0 / Sentinel lymph node in oral cavity squamous cell carcinoma classified as T1 and T2 N0

Introdução: A abordagem cervical em pacientes portadores decarcinoma epidermoide (CE) de cavidade oral classificados comoT1 ou T2 N0 ainda é controversa. A pesquisa do linfonodo sentinela(PLS), representa um menor risco de morbidades para o pacientecom uma boa acurácia para detecção de metástases ocultas.Objetivo: Avaliar a evolução de pacientes submetidos à PLS empescoço clinicamente N0. Método: É um estudo retrospectivoque avaliou os pacientes portadores de CE de cavidade oralclassificados como T1 ou T2 N0 submetidos ressecção do tumorprimário e PLS entre Junho de 2008 até Fevereiro de 2011 noHospital de Câncer de Barretos. Resultados: Foram incluídos 26pacientes, a maioria eram homens (73,0%), a média de idade foide 58 anos e o local mais frequente dos CE foi a língua (50,0%).Os carcinomas foram estadiados como T1 em 8 pacientes (33,3%)e T2 em 16 (66,7%). A PLS mostrou-se positiva em 5 pacientes(19,2%). Todos os pacientes em que a pesquisa do LS mostrousepositiva, foram submetidos a esvaziamento cervical seletivo.O seguimento médio dos pacientes foi de 11 meses, nesteperíodo a recorrência no pescoço homolateral a PLS ocorreu em2 pacientes (7,7%). Conclusão: Neste estudo o LS foi positivo19,2% e a recidiva cervical ocorreu em 7,7%. Observou-se que atécnica de PLS é factível e segura como único procedimento paraestadiamento do pescoço apresentando resultados oncológicoscomparáveis à realização do esvaziamento cervical seletivo comoprimeira opção para estes pacientes.

O valor da marcação tumoral prévia à quimioterapia neoadjuvante e sua relação com a resposta patológica e o tratamento cirúrgico do carcinoma mamário localmente avançado / The role of tumor marking prior to neoadjuvant chemotherapy and its relationship with pathologic response and surgicaltreatment of locally advanced breast cancer

As pacientes com carcinoma de mama localmente avançado da mama são candidatas à quimioterapianeoadjuvante. A grande maioria delas apresenta resposta parcial ao tratamento, isto é, redução dadimensão do tumor. Entretanto, a taxa de resposta patológica completa é de apenas 24%, mesmo nosesquemas mais efetivos, como na associação de antraciclina com taxano. Um dos benefícios da quimioterapianeoadjuvante é a possibilidade da cirurgia conservadora da mama, e um dos desafios é avaliarcom exatidão o grau de resposta tumoral ao tratamento. A resposta clínica é determinada por meiode exames físicos e de imagem, os quais não são suficientes para predizer com acurácia o tamanho dotumor ou a resposta patológica completa em relação ao exame padrão-ouro, que é o histopatológico dapeça cirúrgica. Além disso, é necessário considerar que após a quimioterapia neoadjuvante pode ocorrerfragmentação do tumor, originando-se lesões residuais multifocais, de difícil detecção aos métodosde imagem. Em estudos sobre a quimioterapia neoadjuvante, observou-se que não há uniformidadeno tipo de exame utilizado para a avaliação clinicopatológica da resposta tumoral; não há descriçãoexata sobre a metodologia utilizada na marcação pré-operatória do tumor, e nem sempre toda a áreatumoral pré-quimioterapia neoadjuvante é ressecada, fato que dificulta a avaliação exata da resposta aeste tipo de quimioterapia. Portanto, resta a dúvida: em quais circunstâncias a cirurgia conservadorada mama após a quimioterapia neoadjuvante está bem indicada? Neste artigo, discute-se as diferentesformas de marcação do tumor, a avaliação da resposta patológica e sua importância, principalmentequando se pretende realizar a cirurgia conservadora no carcinoma de mama localmente avançado.

Patients with locally advanced breast carcinoma are candidates for the neoadjuvant chemotherapy.The majority of them have partial response to treatment, i.e., reduction in tumor size; however, therate of pathological complete response is of only 24%, even with the association of anthracycline and taxane. One benefit of the neoadjuvant chemotherapy is the possibility of breast-conserving surgery, and the challenge is the accurate assessment of the tumor response degree to treatment. Clinical response is determined by physical exam and imaging studies, which are not sufficient to predict accurately the tumor size or the pathological complete response in relation to the golden-standard test, which is the surgical histopathology. Moreover, it is necessary to consider that after the neoadjuvant chemotherapy there may be tumor fragmentation, originating multifocal lesions, which are difficult to be detected by imaging methods. In studies regarding neoadjuvant chemotherapy, there is no uniformity in the type of test used for clinical and pathological assessments of tumor response, and there is no exact description of the methodology used in the preoperative markup of the tumor bed, which is not always resected after the neoadjuvant chemotherapy. This is a fact that hinders the accurate assessment of response to the neoadjuvant chemotherapy. Therefore, the question is: under which circumstances a breast-conserving surgery after neoadjuvant chemotherapy is well indicated? This article has discussed the different ways of tumor marking, the evaluation of pathological response and its importance, especially considering breast-conserving treatment of locally advanced breast carcinoma.

Pelvic clear cell adenocarcinoma in a young man: a case report

Clear cell adenocarcinoma is a relatively common neoplasm in the female genital tract, which can also occur in the bladder and urethra. In men, it is a rare neoplasm . We describe the case of a young man with large pelvic mass and diagnosed as clear cell adenocarcinoma. The patient had increased serum levels of CA 125 and carcinoembryonic antigen (CEA) . The tumor was immunohistochemically positive for CA 125 and CK7 and negative for PSA and CK20. Due to the size of the neoplasm at diagnosis and the morphological, immunohistochemical and clinical characteristics, the probable histogenetic origins of the tumor are prostate, prostatic urethra or seminal vesicle.

Adenocarcinoma colorretal: aspectos anatomopatológicos e imuno-histoquímicos do crescimento tumoral, do citoesqueleto e de marcadores de regulação do pH intracelular / Colorectal adenocarcinoma: anatomopathological and imunohistochemical aspects of tumor growth, cytoskeleton and of intracellular pH regulator markers

Centrado no carcinoma colorretal, o presente trabalho visou: 1) Estudar a distribuição das principais variáveis anatomopatológicas, pesquisando sua associação com metástase linfonodal ou hepática. 2) Com base nas eventuais associações encontradas, selecionar um conjunto de variáveis que, estudadas no tumor primário, possam predizer a presença de metástase nodal ou hepática. 3) Analisar os perfis de imunoexpressão de alguns marcadores potencialmente relacionados à citoarquitetura (queratina 7 e 20) e ao crescimento tumoral (proliferação através do Ag Ki-67 e apoptose através da queratina 18 clivada) em amostras de mucosa normal, adenocarcinoma primário, metástase linfonodal e metástase hepática, explorando suas eventuais relações com as variáveis histopatológicas e o estadio da lesão. 4) Pesquisar possíveis associações entre a expressão dos transportadores de monocarboxilato 1, 2 e 4, moléculas reguladoras do pH intracelular, e os marcadores acima relacionados e as variáveis anatomopatológicas. A casuística foi constituída por 139 adenocarcinomas colorretais, sendo 96 sem metástase hepática e 39 com metástase hepática. Os casos foram revistos e 13 variáveis anatomopatológicas foram selecionadas para fazer parte do estudo. Foram confecionados manualmente blocos de microarranjos teciduais (TMA) de mucosa normal, tumor primário, metástase linfonodal e metástase hepática, cujos cortes foram submetidos a estudo imuno-histoquímico utilizando anticorpos anti queratina 7 (K7), queratina 20 (K20), Ki-67 e queratina 18 clivada. Em 126 blocos de parafina de tumores, e 86 amostras de mucosa normal correspondentes foram submetidos a estudo imuno-histoquímico utilizando anticopos anti transportadores de monocarboxilato 1, 2 e 4 (MCT1, MCT2 e MCT 4). A presença de metástase linfonodal asociou-se estatisticamente com a presença de infiltração tumoral além da camada muscular própria (T3 ou T4) (p<0,001), presença de desmoplasia tumoral moderada / intensa (p=0,043), presença...

The aims of this study in colorectal carcinoma were: 1) Verify the distribution of the most important anatomopathological variables, and identifying their relationship with lymph node or liver metastasis. 2) Considering the associations obtained in the first aim, a group of variables was selected to verify the prediction of lymph node or liver metastasis. 3) Analyze the immunoprofile of both markers associated with cytoarchitecture (keratins 7 and 20) and with tumor growth (proliferation and apoptosis using Ki-67 and cleaved keratin 18, respectively) in samples of nontumoral mucosa, primary adenocarcinoma, lymph node metastasis and liver metastasis, exploring the eventual relation with anatomopathological variables and tumor stage. 4) Look for possible associations between molecules related to intracellular pH control, as monocarboxylates transporters 1, 2 and 4, and the markers above mentioned and anatomopathological variables. One hundred and thirty nine colorectal carcinomas is the universe of the casuistic, 96 of them without liver metastasis and 39 metastatic to the liver was studied. Thirteen anatomopathological variables were selected and semi-quantified. We mannualy builted tissue microarrays (TMAs) of non tumoral mucosa, primary adenocarcinoma, lymph node metastasis and liver metastasis. The histological sections from the TMAs were submmitted to immunohistochemical study using antibodies against keratin 7 (K7), keratin 20 (K20), Ag Ki-67 and cleaved keratin 18. In 126 tumor paraffin blocks, 86 of which also had non tumoral mucosa were submitted to immunohistochemical stain using antibodies against monocarboxylate transportes 1, 2 and 4 (MCT1, MCT2 e MCT 4). Lymph node metastasis was associated with tumor infiltration across muscularis propria(p<0,001), moderate / intense desmoplasia(p=0,043), lymph vessel infiltration(p<0,001), venous infiltration (p<0,001) and perineural infiltration (p<0,001). Liver metastasis was statistically associated with tumor...

Neoplasia "borderline" do ovário e gestação: relato de caso / Ovary borderline tumor with pregnancy: a case report

Os autores relatam um caso de uma paciente de 35 anos de idade, tercípara e com história de incompetência istmo-cervical que, durante exames obstétricos iniciais, apresentou massa pélvica à esquerda. A paciente foi encaminhada para o departamento de diagnóstico por imagem, onde se submeteu a avaliação por ultra-sonografia e ressonância magnética. Foi indicada a cirurgia e o tumor foi ressecado, com diagnóstico final de cistadenoma seroso borderline ou de baixo potencial de malignidade. Os principais achados de imagem são descritos e discutidos, associados com breve revisão de literatura.

A case of borderline serous cystadenoma in a 35 years pregnancy woman with previous history of cervix incompetence is reported. This tumor was discovered during initial obstetric exams, and evaluated by ultrasound and magnetic resonance imaging scans. Theauthors describe the clinical and diagnostic finding with a brief review of the literature.