The Unknown microRNA Expression of Male Breast Cancer. Similarities and Differences with Female Ductal Carcinoma. Their Role as Tumor Biomarker.

Mature microRNAs (miRNAs) are small non-protein coding RNAs that modulate gene expression after transcription. Few studies have shown that male breast cancer (MBC) shows distinctive miRNAs pattern, suggesting its relevance in this pathology. To study this, we performed a profile of 800 miRNAs in 9 MBC samples and in normal epithelial cells of 3 MBC cases. EXPERIMENTAL DESIGN: Of FFPE tissues, miRNA was extracted for profiles using the NanoString method. miRNAs were obtained by comparing tumor samples versus normal epithelium. Quantitative real-time PCR analyzes were performed by the TaqMan approach for specific miRNAs. RESULTS: The profile of 800 miRNAs showed a different microRNA expression pattern between MBC and its normal counterpart, suggesting a specific microRNA cancer expression profile for MBC. Forty-nine miRNAs showed greater expression, while 26 were found to be down-regulated in MBC, compared to normal tissue. The lower expression of miR-125b correlated significantly with tumors> 2 cm, suggesting that its down-regulation may be implicated in mechanisms to more aggressive tumors. CONCLUSIONS: These results suggest that MBC has a unique expression profile compared to normal breast tissue and expression profile of female breast cancer. Differentially expressed miRNAs provide insights of this uncommon but highly aggressive pathology.

Urinary Bladder Paragangliomas: How Immunohistochemistry Can Assist to Identify Patients With SDHB Germline and Somatic Mutations.

Urinary bladder paraganglioma (paraganglioma) is a rare tumor of chromaffin cells of the sympathetic system of the urinary bladder wall. We studied 14 cases of this entity and investigated the usefulness of SDHB protein staining by immunohistochemistry (IHC) as a diagnostic tool to identify patients with bladder paragangliomas that could be associated with SDHB gene mutations, as these patients have a more aggressive disease. Eleven tumors from these patients were stained by IHC. Six of 11 tumors were negative for SDHB staining by IHC with no cytoplasmic staining in tumor cells when compared with normal tissues. Five of these 6 negative cases were confirmed to be positive for germline SDHB mutations. One case showed negative staining and no germline SDHB mutation; however, further investigation of the tumor revealed a somatic SDHB gene deletion. The remaining 5 cases showed strong cytoplasmic staining, but they were negative for the presence of SDHB mutation. They were found to be either sporadic tumors or part of von Hippel-Lindau syndrome. Staining for SDHA was positive in all cases. Our study confirms that there is very good correlation between the presence of an SDHB mutation, whether germline or sporadic, and negative SDHB IHC staining in urinary bladder paragangliomas, and this is the first study to demonstrate that somatic mutations can be recognized by IHC staining.

Lymphangitic retroperitoneal carcinomatosis occurring from metastatic sarcomatoid chromophobe renal cell carcinoma.

Forty -five year-old man with left renal mass underwent nephrectomy to reveal 20cm tumor diagnosed as sarcomatoid chromophobe renal cell carcinoma (CRCC). Lymph node metastasis of chromophobe and sarcomatoid components, disseminated tumor in retroperitoneal fat, lymphatic vessels, peri-renal adipose tissue in lymphangitic carcinomatosis pattern were identified. Chromophobe epithelial cells EMA, c-Kit, cytokeratin 7 positive; sarcomatoid cells were CD10, SMA positive with high proliferation index . Chromophobe epithelial cells had loss of heterozygosity (LOH) in chromosomes 1p, 1q while sarcomatoid cells had LOH in 3p,1p, 1q. In conclusion, sarcomatoid CRCC has aggressive biologic behavior and potential to metastasize in unusual patterns.

BRCA1 and BRCA2 mutations in breast cancer patients from Venezuela.

A sample of 58 familial breast cancer patients from Venezuela were screened for germline mutations in the coding sequences and exon-intron boundaries of BRCA1 (MIM no. 113705) and BRCA2 (MIM no. 600185) genes by using conformation-sensitive gel electrophoresis. Ashkenazi Jewish founder mutations were not found in any of the samples. We identified 6 (10.3%) and 4 (6.9%) patients carrying germline mutations in BRCA1 and BRCA2, respectively. Four pathogenic mutations were found in BRCA1, one is a novel mutation (c.951_952insA), while the other three had been previously reported (c.1129_1135insA, c.4603G>T and IVS20+1G>A). We also found 4 pathogenic mutations in BRCA2, two novel mutations (c.2732_2733insA and c.3870_3873delG) and two that have been already reported (c.3036_3039delACAA and c.6024_6025_delTA). In addition, 17 variants of unknown significance (6 BRCA1 variants and 11 BRCA2 variants), 5 BRCA2 variants with no clinical importance and 22 polymorphisms (12 in BRCA1 and 10 in BRCA2) were also identified. This is the first genetic study on BRCA gene mutations conducted in breast cancer patients from Venezuela. The ethnicity of our population, as well as the heterogeneous and broad spectrum of BRCA genes mutations, must be considered to optimize genetic counseling and disease prevention in affected families.

BRCA1 and BRCA2mutations in breast cancer patients from Venezuela

A sample of 58 familial breast cancer patients from Venezuela were screened for germline mutations in the coding sequences and exon-intron boundaries of BRCA1 (MIM no. 113705) and BRCA2 (MIM no. 600185) genes by using conformation-sensitive gel electrophoresis. Ashkenazi Jewish founder mutations were not found in any of the samples. We identified 6 (10.3%) and 4 (6.9%) patients carrying germline mutations in BRCA1 and BRCA2, respectively. Four pathogenic mutations were found in BRCA1, one is a novel mutation (c.951_952insA), while the other three had been previously reported (c.1129_1135insA, c.4603G>T and IVS20+1G>A). We also found 4 pathogenic mutations in BRCA2, two novel mutations (c.2732_2733insA and c.3870_3873delG) and two that have been already reported (c.3036_3039delACAA and c.6024_6025_delTA). In addition, 17 variants of unknown significance (6 BRCA1 variants and 11 BRCA2 variants), 5 BRCA2 variants with no clinical importance and 22 polymorphisms (12 in BRCA1 and10 in BRCA2) were also identified. This is the first genetic study on BRCA gene mutations conducted in breast cancer patients from Venezuela. The ethnicity of our population, as well as the heterogeneous and broad spectrum of BRCA genes mutations, must be considered to optimize genetic counseling and disease prevention in affected families.

Polimorfismos en el promotor del gen del angiotensinógeno (AGT) y su relación con la miocardiopatía chagásica crónica en pacientes venezolanos / Polymorphisms in the promoter of the gene of the angiotensinogen (AGT) and their relation with the chronic chagasic cardiomyopathy in venezuelan patients

La enfermedad de Chagas constituye un importante problema de salud pública en América Latina por presentar elevados índices de prevalencia y por la gravedad de sus cuadros clínicos, tales como la Miocardiopatía Chagásica Crónica (MCC), en la cual los pacientes pueden presentar diferentes grados de alteración cardíaca, siendo los pacientes chagásicos tipo 3 los que presentan mayor compromiso. Por otra parte, se conoce que diversos polimorfismos en el gen del angiotensinógeno (AGT) están correlacionados con el desarrollo de ciertas miocardiopatías hipertróficas. En este trabajo se estudió la posible correlación entre el polimorfismo -6A/G del promotor del gen del AGT con la susceptibilidad al desarrollo de una MCC en pacientes chagásicos tipo 3. Para esto, se estudió una población de 22 pacientes chagásicos tipo 3 (confirmado por seguimientos y parámetros clínicos) y 19 voluntarios seronegativos a Trypanosoma cruzi y sin ningún tipo de alteraciones cardíacas. Los genotipos derivados del polimorfismo -6A/G fueron determinados mediante la técnica de MS-PCR (Mutagenically Separated PCR), utilizando dos iniciadores alelo-específicos para el promotor del gen del AGT. Los resultados obtenidos indican que la distribución de los genotipos GG, AA y AG derivados del polimorfismo -6A/G no difieren significativamente entre pacientes y controles (1, 3, 18 y 1, 2, 16; respectivamente) con un valor de X² obtenido de 0,0983 (p<0,005), lo cual sugiere que el polimorfismo -6A/G en el promotor del gen del AGT no está correlacionado con el desarrollo de MCC presente en estos pacientes