BackgroundHER2 is overexpressed and amplified in approximately 15% of invasive breast cancers, and is the molecular target and predictive marker of response to anti-HER2 agents. In a subset of these cases, heterogeneous distribution of HER2 gene amplification can be found, which creates clinically challenging scenarios. Currently, breast cancers with HER2 amplification/overexpression in just over 10% of cancer cells are considered HER2-positive for clinical purposes; however, it is unclear as to whether the HER2-negative components of such tumors would be driven by distinct genetic alterations. Here we sought to characterize the pathologic and genetic features of the HER2-positive and HER2-negative components of breast cancers with heterogeneous HER2 gene amplification and to define the repertoire of potential driver genetic alterations in the HER2-negative components of these cases.ResultsWe separately analyzed the HER2-negative and HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy number profiling and massively parallel sequencing, and identified potential driver genetic alterations restricted to the HER2-negative cells in each case. In vitro experiments provided functional evidence to suggest that BRF2 and DSN1 overexpression/amplification, and the HER2 I767M mutation may be alterations that compensate for the lack of HER2 amplification in the HER2-negative components of HER2 heterogeneous breast cancers.ConclusionsOur results indicate that even driver genetic alterations, such as HER2 gene amplification, can be heterogeneously distributed within a cancer, and that the HER2-negative components are likely driven by genetic alterations not present in the HER2-positive components, including BRF2 and DSN1 amplification and HER2 somatic mutations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0657-6) contains supplementary material, which is available to authorized users.

Pancreatic heterotopia is rare. Patients with pancreatic ectopia diagnosed by pathological study, whether asymptomatic or with mild symptoms, should be observed. Lesions incidentally detected during surgeries need to be removed by conservative procedures.

Clinical variables had no influence on the patients' prognosis. Among the macroscopic variables, the form of the neoplasia and its involvement in the intestinal circumference did influence the patients' prognosis. These last two variables are important data capable of contributing to the identification of patient subpopulations with greater or lesser prognostic risk.

This immunohistochemical method can be employed successfully in the detection of neoplastic cells in lymph nodes previously considered free. In this study, there was a trend towards lower survival in node-positive patients but this did not reach statistical significance.

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Short-bowel syndrome is responsible for significant metabolic alterations that compromise nutritional status. Glutamine is considered an essential nutrient for enterocytes, so beneficial effects from supplementation of the diet with glutamine are hypothesized.PURPOSE: In this study, the effect of a diet enriched with glutamine was evaluated in rats undergoing extensive small bowel resection, with analysis of postoperative weight loss and intestinal morphometrics of villi height, crypt depth, and thickness of the duodenal and remnant jejunal mucosa.METHODS: Three groups of male Wistar rats were established receiving the following diets: with glutamine, without glutamine, and the standard diet of laboratory ration. All animals underwent an extensive small bowel resection, including the ileocecal valve, leaving a remnant jejunum of only 25 cm from the pylorus that was anastomosed lateral-laterally to the ascendant colon. The animals were weighed at the beginning and end of the experiment (20 th postoperative day). Then they were killed and the remnant intestine was removed. Fragments of duodenal and jejunal mucosa were collected from the remnant intestine and submitted to histopathologic exam. The morphometric study of the intestinal mucosa was accomplished using a digital system (KS 300) connected to an optic microscope. Morphometrics included villi height, crypt depth, and the total thickness of intestinal mucosa. RESULTS:The weight loss comparison among the 3 groups showed no significant loss difference. The morphometric studies showed significantly taller duodenal villi in the glutamine group in comparison to the without glutamine group, but not different from the standard diet group. The measurements obtained comparing the 3 groups for villi height, crypt depth, and thickness of the remnant jejunum mucosa were greater in the glutamine-enriched diet group than for the withoutglutamine diet group, though not significantly different from with standard-diet group.CONCLUSIONS: In rats with experimentally produced short-bowel syndrome, glutamine-enrichment of an isonitrogenous test diet was associated with an improved adaptation response by the intestinal mucosa but not reduced weight loss. However, the adaptation response in the group receiving the glutamine-enriched diet was not improved over that for the group fed regular chow.

Objective:To describe the flow and costs associated with the diagnosis and treatment of patients with breast cancer who come from the public healthcare system and were treated at Hospital Israelita Albert Einstein.Methods:Between August 2009, and December 2011, 51 patients referred by the Unified Public Healthcare System (SUS) had access to Hospital Israelita Albert Einstein for diagnostic radiology, medical oncology, radiotherapy, and oncologic/ breast reconstruction surgery. The data were collected retrospectively from the hospital records, patient charts, pharmacy records, and from the hospital billing system.Results:The total sum spent for diagnosis and treatment of these 51 patients was US$ 1,457,500.00. This value encompassed expenses with a total of 85 hospitalizations, 2,875 outpatient visits, 16 emergency room visits, and all expenses associated with these stays at the hospital. The expenditure for treatment of each patient submitted to biopsy, breast conserving surgery, adjuvant chemotherapy without trastuzumab (a regime with taxane followed by anthracycline), radiotherapy, and 5 years of tamoxifen was approximately US$ 25,500.00.Conclusion:Strategies for cost-reduction of treatment in the private setting are necessary to enable future large-scale public-private partnerships in oncology.

Lymph node (LN) is a secondary lymphoid organ with highly organized and compartmentalized structure. LNs harbor B, T, and other cells among fibroblastic reticular cells (FRCs). FRCs are characterized by both podoplanin (PDPN/gp38) expression and by the lack of CD31 expression. FRCs are involved in several immune response processes but mechanisms underlying their function are still under investigation. Double-negative cells (DNCs), another cell population within LNs, are even less understood. They do not express PDPN or CD31, their localization within the LN is unknown, and their phenotype and function remain to be elucidated. This study evaluates the gene expression and cytokines and chemokines profile of human LN-derived FRCs and DNCs during homeostasis and following inflammatory stimuli. Cytokines and chemokines secreted by human FRCs and DNCs partially diverged from those identified in murine models that used similar stimulation. Cytokine and chemokine secretion and their receptors expression levels differed between stimulated DNCs and FRCs, with FRCs expressing a broader range of chemokines. Additionally, dendritic cells demonstrated increased migration toward FRCs, possibly due to chemokine-induced chemotaxis since migration was significantly decreased upon neutralization of secreted CCL2 and CCL20. Our study contributes to the understanding of the biology and functions of FRCs and DNCs and, accordingly, of the mechanisms involving them in immune cells activation and migration.