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Lynch syndrome screening by NGS in endometrial cancer allows concurrent molecular classification with one test. PURPOSE: To assess implementation of a next-generation sequencing (NGS) assay to detect microsatellite instability (MSI) as a screen for Lynch syndrome (LS) in endometrial cancer (EC), while determining and comparing characteristics of the four molecular subtypes. METHODS: A retrospective review was performed of 408 total patients with newly diagnosed EC: 140 patients who underwent universal screening with NGS and 268 patients who underwent screening via mismatch repair immunohistochemistry (MMR IHC) as part of a historical screening paradigm. In the NGS cohort, incidental POLE and TP53 mutations along with MSI were identified and used to characterize EC into molecular subtypes: POLE -ultramutated, MSI high (MSI-H), TP53 -mutated, and no specific molecular profile (NSMP). In historical cohorts, age- and/or family history–directed screening was performed with MMR IHC. Statistical analysis was performed using a t -test for continuous variables and chi-square or Fisher's exact test for categorical variables. RESULTS: In the NGS cohort, 38 subjects (27%) had MSI-H EC, 100 (71%) had microsatellite stable EC, and two (1%) had an indeterminate result. LS was diagnosed in two subjects (1%), and all but five patients completed genetic screening (96%). Molecular subtypes were ascertained: eight had POLE -ultramutated EC, 28 had TP53 -mutated EC (20%), and 66 (47%) had NSMP. MSI-H and TP53 -mutated EC had worse prognostic features compared with NSMP EC. Comparison with historical cohorts demonstrated a significant increase in follow-up testing after an initial positive genetic screen in the MSI NGS cohort (56% v 89%; P =.001). CONCLUSION: MSI by NGS allowed for simultaneous screening for LS and categorization of EC into molecular subtypes with prognostic and therapeutic implications. [ABSTRACT FROM AUTHOR]

Primary biphasic tumors of the lung are rare. Lung lesions with a biphasic pattern are far more commonly primary or metastatic soft tissue tumors with entrapped native respiratory epithelium, giving the false impression of a biphasic tumor. We report a case of bilateral benign metastasizing leiomyomas in a 69-year-old female where the tumor cells diffusely entrapped native respiratory glands in a phyllodes-like pattern. The radiographic characteristics and histologic appearance were not immediately diagnostic and covered a wide differential. Reaching the final diagnosis required the use of immunohistochemical studies as well as correlation with the patient's history and radiographic findings. To the best of our knowledge, this is the first report of pulmonary benign metastasizing leiomyoma presenting in a phyllodes-like pattern. This case illustrates the importance of considering entrapment of native lung epithelium in the differential diagnosis of biphasic-appearing lung tumors. [ABSTRACT FROM AUTHOR]

Aims: Basal‐like breast cancer is an aggressive molecular subtype associated with younger age and early relapse. Most cases lack expression of oestrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2, limiting targeted therapeutic options. Basal‐like breast cancer is defined by the expression of genes in the outer/basally located epithelial layer of mammary glands, including those encoding cytokeratin (CK) 5 and CK14, and epidermal growth factor receptor (EGFR). SRY‐box transcription factor 10 (SOX10), for which there is a readily available immunohistochemical stain, is expressed in a subset of breast cancers, particularly triple‐negative carcinomas. In this study, we sought to: (i) assess the association between SOX10 expression and intrinsic molecular subtypes as defined by Prediction Analysis of Microarray 50 (PAM50) gene expression; and (ii) compare the performance of SOX10 with that of other surrogate markers of the basal‐like subtype, including CK5, EGFR, nestin, and inositol polyphosphate 4‐phosphatase type II (INPP4B). Methods and results: SOX10 immunostaining was performed on tissue microarrays constructed from a contemporary series enriched for ER‐negative and weakly ER‐positive cancers that had also undergone PAM50 gene profiling. A total of 211 cases were informative for both SOX10 immunohistochemistry and PAM50 subtype, including 103 basal‐like cancers. Staining for SOX10 was positive in 73 of 103 basal‐like cancers and in only two of 108 cancers of other subtypes (P < 0.001), resulting in a sensitivity of 70.9% and a specificity of 98.1%. SOX10 was more specific than the other tested basal markers, and the results were independent of ER status. Conclusions: SOX10 is a moderately sensitive, but highly specific, immunohistochemical biomarker for the basal‐like intrinsic subtype of breast cancer, which, unlike other commonly used immunohistochemical biomarkers, is independent of hormone receptor status. [ABSTRACT FROM AUTHOR]

Abstract Background Schools are the most frequent target for intervention programs aimed at preventing child obesity; however, the overall effectiveness of these programs has been limited. It has therefore been recommended that interventions target multiple ecological levels (community, family, school and individual) to have greater success in changing risk behaviors for obesity. This study examined the immediate and short-term, sustained effects of the Switch program, which targeted three behaviors (decreasing children's screen time, increasing fruit and vegetable consumption, and increasing physical activity) at three ecological levels (the family, school, and community). Methods Participants were 1,323 children and their parents from 10 schools in two states. Schools were matched and randomly assigned to treatment and control. Measures of the key behaviors and body mass index were collected at baseline, immediately post-intervention, and 6 months post-intervention. Results The effect sizes of the differences between treatment and control groups ranged between small (Cohen's d = 0.15 for body mass index at 6 months post-intervention) to large (1.38; parent report of screen time at 6 months post-intervention), controlling for baseline levels. There was a significant difference in parent-reported screen time at post-intervention in the experimental group, and this effect was maintained at 6 months post-intervention (a difference of about 2 hours/week). The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant. At the 6-month follow-up, parent-reported screen time was significantly lower, and parent and child-reported fruit and vegetable consumption was significantly increased. There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group. The intervention effects were moderated by child sex (for fruit and vegetable consumption, physical activity, and weight status), family involvement (for fruit and vegetable consumption), and child body mass index (for screen time). The perception of change among the experimental group was generally positive with 23% to 62% indicating positive changes in behaviors. Conclusion The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children's fruit and vegetable consumption and minimizing screen time. The Switch program offers promise for use in youth obesity prevention.

Abstract Background Although several previous projects have attempted to address the issue of child obesity through school-based interventions, the overall effectiveness of school-based programs on health-related outcomes in youth has been poor. Thus, it has been suggested that multi-level interventions that aim to influence healthy lifestyle behaviors at the community, school and family levels may prove more successful in the prevention of childhood obesity. Methods/Design This paper describes the rationale, design, and implementation of a community-, school-, and family-based intervention aimed at modifying key behaviors (physical activity, screen time (Internet, television, video games), and nutrition) related to childhood obesity among third through fifth graders in two mid-western cities. The intervention involves a randomized study of 10 schools (5 intervention and 5 control schools). The intervention is being conducted during the duration of the academic year – approximately 9 months – and includes baseline and post-intervention measurements of physical activity, dietary intake, screen time and body composition. Discussion We hope this report will be useful to researchers, public health professionals, and school administrators and health professionals (nurses and physical/health educators) seeking to develop similar prevention programs. It is obvious that more collaborative, inter-disciplinary, multi-level work is needed before a proven, effective intervention package to modify behaviors related to childhood obesity can be generally recommended. It is our hope that SWITCH is a step in that direction. Trial Registration ClinicalTrials.gov NCT00685555

Introduction Indigenous people face poor health outcomes in comparison with the Canadian population [1,2]. In remote indigenous communities, the health impacts of historical and systemic disadvantage are compounded by geographic [...]

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Copyright of Canadian Journal of Pathology is the property of Canadian Association of Pathologists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Kevin Callan, wrongly imprisoned for the alleged murder of his four-year-old stepdaughter, has sympathy for the many hundreds of prisoners who he believes have also been wrongly convicted. Callan feels particular sympathy for British-born murderer Nick Ingram who was executed in Georgia, in case he was also innocent. Callan fought for his own release by seeking medical knowledge to show the child did not die because of shaking, as claimed in court, but because of brain injury incurred by a fall. Callan was convicted of the crime, even though the child's mother gave evidence in his favour.