Somatic mutations in early onset luminal breast cancer.

Breast cancer arising in very young patients may be biologically distinct; however, these tumors have been less well studied. We characterized a group of very young patients (≤ 35 years) for BRCA germline mutation and for somatic mutations in luminal (HER2 negative) breast cancer. Thirteen of 79 unselected very young patients were BRCA1/2 germline mutation carriers. Of the non-BRCA tumors, eight with luminal subtype (HER2 negative) were submitted for whole exome sequencing and integrated with 29 luminal samples from the COSMIC database or previous literature for analysis. We identified C to T single nucleotide variants (SNVs) as the most common base-change. A median of six candidate driver genes was mutated by SNVs in each sample and the most frequently mutated genes were PIK3CA, GATA3, TP53 and MAP2K4. Potential cancer drivers affected in the present non-BRCA tumors include GRHL2, PIK3AP1, CACNA1E, SEMA6D, SMURF2, RSBN1 and MTHFD2. Sixteen out of 37 luminal tumors (43%) harbored SNVs in DNA repair genes, such as ATR, BAP1, ERCC6, FANCD2, FANCL, MLH1, MUTYH, PALB2, POLD1, POLE, RAD9A, RAD51 and TP53, and 54% presented pathogenic mutations (frameshift or nonsense) in at least one gene involved in gene transcription. The differential biology of luminal early-age onset breast cancer needs a deeper genomic investigation.

Calcitriol supplementation effects on Ki67 expression and transcriptional profile of breast cancer specimens from post-menopausal patients.

BACKGROUND & AIMS: High concentration of 1,25(OH)2D3 (50-100 nM), which cause hypercalcemia in vivo, induce the hormone transcriptional targets and exert antiproliferative effects in cultured breast cancer lineages, however, no studies investigated whether these effects might be reproduced in tumor specimens in vivo. Our aim was to evaluate the effects of calcitriol supplementation on the proliferative index (Ki67 expression) and gene expression profile of post-menopausal breast cancer samples. METHODS & RESULTS: Tumor samples were collected from 33 patients, most of whom (87.5%) presenting 25(OH)D3 insufficiency, before and after a short term calcitriol supplementation (0.50 µg/day PO, for 30 days). Tumor dimension remained stable in ultrasound evaluations. A slight reduction in Ki67 immunoexpression was detected, however in only 10/32 post-calcitriol samples an expressively low proliferative index [Ln (%Ki67+) < 1] was achieved. Gene expression from 15 matched pre/post-supplementation samples was analyzed by microarray (U133 Plus 2.0 GeneChip, Affymetrix) and 15 genes were over-expressed in post-supplementation tumors, including FOS and EGR1, which were previously shown to be regulated by vitamin D. However, these results were not confirmed in another four breast cancer samples. CONCLUSIONS: Calcitriol supplementation is neither sufficient to expressively elicit an antiproliferative response nor to induce the hormone transcriptional signaling pathway in breast cancer specimens.

Granuloma Piogênico: descrição de dois casos incomuns e revisão da literatura / Pyogenic granuloma: description of two unusual cases and review of the literature

Granuloma piogênico é proliferação vascular benigna e comum, geralmente secundária a eventos como trauma cutâneo. É sabido que algumas lesões podem mimetizar o melanoma e vice-versa, sendo recomendadas remoção cirúrgica e análise anatomopatológica. O advento de tecnologias que ampliam a imagem reconhecida pelo olho, como a dermatoscopia, através da identificação de algumas estruturas e determinação de padrões específicos, pode facilitar essa diferenciação e ajudar na tomada de decisões. Em situações raras, sua apresentação clínica mostra-se inusitada, e o objetivo deste artigo é demonstrar esse fato e revisar a literatura médica sobre o assunto, com foco nos achados dermatoscópicos.

Pyogenic granuloma is a common, benign, vascular proliferation, usually secondary to other events, such as cutaneous trauma. It is known that some lesions can mimic melanoma and vice versa, and it is recommended that the lesion be surgically removed and analyzed histologically. The advent of technologies-such as dermoscopy-that amplify the image recognized by the eye through the identification of certain structures and specific patterns, can facilitate this differentiation and assist in decision-making. In rare situations, its clinical presentation is unusual. The current article is aimed at demonstrating this fact and reviewing the medical literature on the subject, focusing on dermoscopic findings.

Avaliação da distância entre a origem do tronco celíaco e da artéria mesentérica superior (nota prévia) / Distance evaluation between the origin of the celiac trunk and from the superior mesenteric artery (advance notice)

Os autores, em decorrência das controvérsias existentes na literatura e tendo em vista a necessidade de parâmetros confiáveis, os quais são cada vez mais solicitados, avaliaram a distância entre o tronco celíaco e a artéria mesentérica superior, pela face interna da artéria aorta abdominal em 25 casos.

As result of the controverses that exists in the literature andconsidering the necessity for reliable standards, which are moreand more demanded, the authors measured the distance betweenthe celiac trunk and the superior mesenteric artery, through theinternal side of the abdominal aorta in 25 cases.