Mutation profiling in the PIK3CA, TP53, and CDKN2A genes in circulating free DNA and impalpable breast lesions.

Breast impalpable lesions have become a clinical dilemma because they are small, presenting a heterogeneous cellular phenotype. The aim of this study was to evaluate the mutational profile of the PIK3CA, TP53, and CDKN2A genes, comparing the mammary tissue with the respective circulating free DNA (cfDNA). The PIK3CA, TP53, and CDKN2A genes were sequenced (PCR-Sanger) in 58 women with impalpable lesions (49 malignant and 9 benign) with the respective cfDNA. The chi-square or Fisher's exact test was used to evaluate statistical significance between the clinical variables and mutational profile. A total of 51 out of 58 samples generated successful mutation profiles in both breast lesion and cfDNA. Of the 37 mutations detected, 10 (27%) and 16 (43%) mutations were detected in benign and malignant breast lesions, respectively, while 2 (5%) and 9 (24%) were found in cfDNA of women with benign and malignant lesions, respectively. The lymph node involvement with mutations in the PIK3CA in malignant lesions (P = 0.001), and the relationship between mutations in PIK3CA, comparing ductal tumors with benign lesions (P = 0.05), were statistically significant. This study detected different mutations in PIK3CA, TP53, and CDKN2A genes, which represent, in part, the heterogeneity of impalpable lesions. The results confirm that more studies should be conducted on the functional role of cfDNA in the impalpable lesions.

Epithelioid hemangioendothelioma: 15 years at the National Cancer Institute. Literature review / Hemangioendotelioma epitelioide: 15 anos no Instituto Nacional de Câncer. Revisão da literatura

INTRODUCTION: Hemangioendotheliomas are locally aggressive vascular tumors with intermediate malignity and metastasis risk. The epithelioid variant, the most aggressive one, equally affects men and women at any age and it is rare in children. It occurs as a solitary tumor, which is usually painful, affecting superficial or deep soft tissues. Furthermore, it is less frequent in the liver, lung, bones, skin, lymph nodes and central nervous system. Microscopically, they present epithelioid cells with intracytoplasmic vacuoles, low mitotic activity and little or no necrosis. Additionally, its vascular nature is confirmed by immunohistochemical studies (CD31, CD34 and factor VIII). OBJECTIVE, MATERIAL AND METHODS: Through search in the archives of the Pathology Division of the National Cancer Institute (Instituto Nacional de Câncer [INCA]) from 1996 to 2011, 13 cases of epithelioid hemangioendothelioma (HEE) were identified and analyzed. RESULTS AND DISCUSSION: seven cases occurred in male patients and six in female patients, mean age 42 years, ranging from 7-66. The most common locations were: soft tissue (three patients; 23%); head and neck, mediastinum, bone and lung (two patients each; 15%); liver and lymph nodes (one patient each; 8%). There was clinical follow-up of nine patients: five were alive and disease-free (one to six years after diagnosis); three out of four patients with aggressive disease progressed to death (one month to five years after diagnosis); one relapsed two years after diagnosis and is alive with disease. CONCLUSION: This series of 13 cases of HEE, whose diagnoses were based on morphological and/or immunohistochemical analyses, demonstrates the different patterns of clinical presentation and biologic behavior of this disease.

INTRODUÇÃO: O hemangioendotelioma é um tumor vascular de malignidade intermediária, localmente agressivo e com risco de metástase. A variante epitelioide, a mais agressiva, acomete igualmente homens e mulheres em qualquer idade e é rara na infância. Apresenta-se como tumoração solitária, geralmente dolorosa, em partes moles, superficiais ou profundas; menos frequentemente, acomete fígado, pulmão, ossos, pele, linfonodos e sistema nervoso central. Microscopicamente, mostram células epitelioides com vacúolos intracitoplasmáticos, baixa atividade mitótica, pouca ou nenhuma necrose, tendo sua natureza vascular comprovada por estudos imuno-histoquímicos (CD31, CD34, Fator VIII). OBJETIVOS E MATERIAL E MÉTODOS: Por meio de busca nos arquivos da Divisão de Patologia (DIPAT) do Instituto Nacional de Câncer (INCA), de 1996 a 2011, foram encontrados e revisados 13 casos de hemangioendotelioma epitelioide (HEE). RESULTADOS E DISCUSSÃO: Sete casos ocorreram em homens e seis, em mulheres, com idade média de 42 anos, variando de 7 a 66 anos de idade. As localizações mais frequentes foram partes moles (três pacientes; 23%); cabeça-pescoço, mediastino, osso e pulmão, (dois pacientes cada; 15%); fígado e linfonodo (um paciente cada; 8%). Houve seguimento clínico de nove pacientes: cinco estavam vivos e livres de doença (de um a seis anos após o diagnóstico); dos quatro pacientes que apresentaram HEE agressiva, três evoluíram a óbito com doença (de um mês a cinco anos) e um recidivou dois anos após o diagnóstico e está vivo com a doença. CONCLUSÃO: Esta série de 13 casos de HEE, cujos diagnósticos foram firmados em bases morfológicas e/ou imuno-histoquímicas, demonstra os diferentes padrões de apresentação clínica e o comportamento biológico da doença.

Centroblastic diffuse large B cell lymphoma displays distinct expression pattern and prognostic role of apoptosis resistance related proteins.

Centroblastic diffuse large B cell lymphoma (DLBCL) samples were analyzed by immunohistochemistry to evaluate the expression of p53, Bcl-2, Survivin, XIAP, and Ki-67. Survivin was the only protein which expression exhibited a trend for impact in progression-free (p = .077) and overall survival (p = .054). In the Mann-Whitney test, Survivin expression correlated with a negative overall survival (p = .045). These results appeared to be intimately related to Survivin cytoplasmic localization. Moreover, the anti-apoptotic proteins Bcl-2 and Survivin were less frequent in centroblastic DLBCL. Our results indicate that centroblastic DLBCL may be a disease with characteristic biology and clinical course and, therefore, specific prognostic factors.

Differences in the expression pattern of P-glycoprotein and MRP1 in low-grade and high-grade gliomas.

Multidrug resistance in gliomas is the major challenges in the clinical setting. We investigated the expression of P-glycoprotein (Pgp) and multidrug resistance-related protein 1 (MRP1) in 50 gliomas using immunohistochemistry. Compared to Pgp, MRP1 positivity was observed in highest percentage of gliomas grade IV samples (p = 0.008). Unlike MRP1 expression observed in high-grade, gliomas grade II exhibited a greater number of Pgp positive samples as compared to grades III and IV (p = 0.026). Our results suggest that the difference between the histological grade gliomas regarding MRP1 and Pgp expression must have implications in the choice of chemotherapeutic protocols.