The dual role of the X-linked FoxP3 gene in human cancers

The FoxP3 (forkhead box P3) gene is an X-linked gene that is submitted to inactivation. It is an essential transcription factor in CD4(+)CD25(+)FoxP3 regulatory T cells, which are therapeutic targets in disseminated cutaneous melanoma. Moreover, FoxP3 is an important tumor suppressor gene in carcinomas and has putative cancer suppressor gene function in cutaneous melanoma as well. Therefore understanding the structure and function of the FoxP3 gene is crucial to gaining insight into the biology of melanoma to better develop immunotherapeutics and future therapeutic strategies

Diagnostic yield of NanoString nCounter FusionPlex profiling in soft tissue tumors

Diagnostic histopathology of soft tissue tumors can be troublesome as many entities are quite rare and have overlapping morphologic features. Many soft tissue tumors harbor tumor-defining gene translocations, which may provide an important ancillary tool for tumor diagnosis. The NanoString nCounter platform enables multiplex detection of pre-defined gene fusion transcripts in formalin-fixed and paraffin-embedded tissue. A cohort of 104 soft tissue tumors representing 20 different histological types was analyzed for the expression of 174 unique gene fusion transcripts. A tumor-defining gene fusion transcript was detected in 60 cases (58%). Sensitivity and specificity of the NanoString assay calculated against the result of an alternative molecular method were 85% and 100%, respectively. Highest diagnostic coverage was obtained for Ewing sarcoma, synovial sarcoma, myxoid liposarcoma, alveolar rhabdomyosarcoma, and desmoplastic small round cell tumor. For these tumor types, the NanoString assay is a rapid, cost-effective, sensitive, and specific ancillary screening tool for molecular diagnosis. For other sarcomas, additional molecular testing may be required when a translocation transcript is not identified with the current 174 gene fusion panel

Angiosarcomatous transdifferentiation of metastatic melanoma

Melanoma is known to show considerable variation in its histopathological presentation. In exceptional cases, heterologous or divergent differentiation (metaplastic melanoma) can be observed. We report a case of a 69-year-old man who was diagnosed with nodular melanoma on the right upper leg. One year later, the patient presented with an inguinal lymph node metastasis and a lymph node dissection was carried out. In two out of five positive lymph nodes, an angiosarcomatous component was found next to a conventional melanoma component. Shortly after, the patient developed two in-transit metastases in which again an angiosarcomatous component was seen. The vascular component stained positive for ERG and CD31 and negative for melanocytic markers (Mart-1, S100, SOX-10), while the conventional melanoma had an opposite staining pattern. Molecular analysis on both components showed an identical mutation in the NRAS gene, which in our opinion proves the divergent differentiation. To the best of our knowledge, this is the first case report describing angiosarcomatous transdifferentiation of melanoma

Imaging-Based Surrogate Markers of Epidermal Growth Factor Receptor Mutation in Lung Adenocarcinoma:A Local Perspective

Purpose: To identify computed tomography (CT) features of epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma in Canadian population and whether imaging-based surrogate markers of EGFR mutation in our population were similar to those found in the Asian population. Materials and Methods: Pretreatment CT scans of 223 patients with adenocarcinoma of the lung (112 with EGFR mutation and 111 without mutation) were retrospectively assessed for 20 specific CT features by 2 radiologists, who were blinded to the status of EGFR mutation. Univariate and multivariate logistic regression analyses as well as areas under the receiver operating characteristic curve were performed to discriminate characteristics of EGFR-activating mutation features. Results: Epidermal growth factor receptor mutation-positive adenocarcinomas were more frequently found in female (P <.03), less than 20 pack-year smoking history (P <.001), smaller tumor (P <.01), spiculated margins (P <.05), without centrilobular emphysema (P <.001), and without lymphadenopathy (P <.05), similarly to the Asian population. Multivariate logistic regression analyses of combined clinical and radiological features identified less than 20 pack-year smoking history, smaller tumor diameter, fine or coarse spiculations, noncentral location of the tumor, and lack of centrilobular emphysema and pleural attachment as the strongest independent prognostic factors for the presence of an EGFR mutation. These combined features improved prognostic ability area under the curve to 0.879, compared to 0.788 for clinical features only. Conclusion: Several CT findings may help predict the presence of an activating mutation in EGFR in lung adenocarcinomas in our Canadian population. Combining clinical and radiological features improves prognostic ability to determine the EGFR mutation status compared to clinical features alone

Agricultural biomass as provisioning ecosystem service: quantification of energy flows

Agro-ecosystems supply provisioning, regulating and cultural services to human society. This study focuses on the agro-ecosystem provisioning services regarding the production of agricultural biomass. These services strongly respond to the socio-economic demands of human beings, and are characterised by an injection of energy in the ecosystems production cycle which is often exceeding the ecological capacity of the ecosystem, i.e. the overall ability of the ecosystem to produce goods and services linked to its bio-physical structure and processes that take place during the agricultural production. Agricultural production is identified as ecosystem service in widely recognised ecosystem service frameworks, but currently there is no clear agreement within the scientific and policy communities on how the ecological-socio-economic flow linked to this provisioning service should be assessed, beyond a mere accounting of yields. This study attempts to provide a new insight to this issue by proposing an approach based on the energy budget, which takes into consideration the energy needed by the ecosystem to supply the service. The approach is based on the concepts of Energy Return on Investment (EROI) and Net Energy Balance (NEB), and considers different bio-physical structures and processes of agro-ecosystems. The work is structured in three parts: the first aims at estimating inputs (machinery, seeds, fertilizers, irrigation, labour) in energy terms; the second at estimating biomass output in energy terms; the third to compare actual agricultural production with three reference scenarios encompassing a range of human input (no input – low input – high input scenarios). Results show that in general terms cereal and grassland systems have the largest energy gains (both in terms of EROI and NEB). Such systems are characterised by a lower economic value of their output compared to other producing systems such as fruits, which have lower energy gains but a higher embodied energy, which is recognized in the market as valuable. Comparison of actual production systems with the high input scenario confirms that current production in Europe is already highly intensive, and that increasing the energy input would not improve the efficiency of the conversion of such additional energy into biomass. Overall, the proposed approach seems a useful tool to identify which are the factors in the agricultural production process that could be modified to improve the energy efficiency in agricultural systems and the sustainability of their production. This study can be considered as a first step in the assessment of the total energy balance of the agro-ecosystem. In fact it deals with the quantification of energy regarding human inputs and the corresponding output and further analysis should address crucial issues such as the quality of the energy and the embodied energy in the plant production, which will help to understand the full complexity of the agro-ecosystemJRC.H.4-Monitoring Agricultural Resource

L1CAM Expression is Related to Non-Endometrioid Histology, and Prognostic for Poor Outcome in Endometrioid Endometrial Carcinoma

The majority of endometrial carcinomas are classified as Type I endometrioid endometrial carcinomas (EECs) and have a good prognosis. Type II non-endometrioid endometrial carcinomas (NEECs) have a significant worse outcome. Yet, 20 % of the EECs are associated with an unexplained poor outcome. The aim of this study was to determine if L1CAM expression, a recently reported biomarker for aggressive tumor behavior in endometrial carcinoma, was associated with clinicopathological features of EECs. A total of 103 patients diagnosed as EEC at the Radboud University Medical Centre, based on the pathology report were selected. L1CAM status of these tumors was determined, and histologic slides were reviewed by two expert pathologists. L1CAM-positivity was observed in 17 % (18/103). Review of the diagnostic slides revealed that 11 out of these 18 L1CAM-positive tumors (61 %) contained a serous- or mixed carcinoma component that was not initially mentioned in the pathology report. L1CAM-expression was associated with advanced age, poor tumor grade, and lymphovascular space invasion. A worse five year progression free survival rate was observed for patients with L1CAM-positive tumors (55.6 % for the L1CAM-positive group, compared to 83.3 % for the L1CAM-negative group P = 0.01). L1CAM expression carries prognostic value for histologically classified EEC and supports the identification of tumors with a NEEC component. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12253-016-0047-8) contains supplementary material, which is available to authorized users

Evaluating an intervention to reduce fear of falling and associated activity restriction in elderly persons: design of a randomised controlled trial [ISRCTN43792817]

BACKGROUND: Fear of falling and associated activity restriction is common in older persons living in the community. Adverse consequences of fear of falling and associated activity restriction, like functional decline and falls, may have a major impact on physical, mental and social functioning of these persons. This paper presents the design of a trial evaluating a cognitive behavioural group intervention to reduce fear of falling and associated activity restriction in older persons living in the community. METHODS/DESIGN: A two-group randomised controlled trial was developed to evaluate the intervention. Persons 70 years of age or over and still living in the community were eligible for study if they experienced at least some fear of falling and associated activity restriction. A random community sample of elderly people was screened for eligibility; those eligible for study were measured at baseline and were subsequently allocated to the intervention or control group. Follow-up measurements were carried out directly after the intervention period, and then at six months and 12 months after the intervention. People allocated to the intervention group were invited to participate in eight weekly sessions of two hours each and a booster session. This booster session was conducted before the follow-up measurement at six months after the intervention. People allocated to the control group received no intervention as a result of this trial. Both an effect evaluation and a process evaluation were performed. The primary outcome measures of the effect evaluation are fear of falling, avoidance of activity due to fear of falling, and daily activity. The secondary outcome measures are perceived general health, self-rated life satisfaction, activities of daily life, feelings of anxiety, symptoms of depression, social support interactions, feelings of loneliness, falls, perceived consequences of falling, and perceived risk of falling. The outcomes of the process evaluation comprise the performance of the intervention according to protocol, the attendance and adherence of participants, and the participants' and facilitators' opinion about the intervention. Data of the effect evaluation will be analysed according the intention-to-treat and on-treatment principle. Data of the process evaluation will be analysed using descriptive techniques