Activity

The aim of the study was to investigate the advantage of implementing next-generation sequencing (NGS) compared with quantitative polymerase chain reaction (qPCR) when performing routine molecular diagnostics in adenocarcinomas of the lung.

The study is a retrospective cross-sectional observational study of 1839 cytological and histological adenocarcinoma biopsies investigated for gene mutations from 2016 to 2018 at the Department of Pathology at Aarhus University Hospital. A total of 1169 samples were analyzed by qPCR for the presence of EGFR hotspot mutations from 2016 to 2017. A total of 670 samples were analyzed with NGS for the presence of EGFR mutations and other gene mutations in 2018.

The average frequency of EGFR mutations in the study population was 11.5%, with the highest frequency found in 2018, where NGS was implemented (10.8% in 2016, 11.5% in 2017, and 12.2% in 2018). Possible therapy resistance markers such as EGFR exon 20 mutations were found more commonly after NGS implementation, the difference being statistically significant (P=.015). In addition, NGS (2018) showed that 40.6% of the samples had KRAS mutations and 6.0% had BRAF mutations, mutations not commonly investigated in lung adenocarcinomas when qPCR is the method of choice. Amongthe EGFR-mutated samples analyzed with NGS, 13 contained a concurrent EGFR mutation, whereas three and two contained a concurrent KRAS and BRAF mutations, respectively.

With the implementation in a clinical setting, NGS identifies more uncommon but potentially clinically important EGFR mutations, unique combinations of EGFR mutations, and concurrent mutations in KRAS and BRAF.

With the implementation in a clinical setting, NGS identifies more uncommon but potentially clinically important EGFR mutations, unique combinations of EGFR mutations, and concurrent mutations in KRAS and BRAF.Renal cell tumors with oncocytic phenotypes represent a daily challenge, with several novel, emerging, and provisional entities enriching the diagnostic repertoire. Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), low-grade oncocytic tumor (LOT), and eosinophilic vacuolated tumor (EVT) have been recognized as unique entities, although their distinctive nature remains controversial. Although most of these tumors are sporadic, rare reports of similar tumors in tuberous sclerosis complex (TSC) have been published. We describe multifocal, often bilateral, tumors in six patients without personal or family history of syndromic diseases. More than 60 tumors in various combinations were identified in 10 nephrectomies and one biopsy encompassing ESC-RCC (n = 6), LOT (n = 14), EVT (n = 1), clear cell RCC with fibromyomatous stroma (n = 12), clear cell RCC (n = 2), angiomyolipomas (AMLs; n > 20), unclassified renal cell tumors (n = 2), papillary adenomas (n = 4), and renomedullary interstitial cell tumor (n = 1). TSC1 germline pathogenic mutations were confirmed in two patients. A tumor without germline testing in a third patient revealed TSC1 biallelic inactivation. Two additional patients had molecular testing, which excluded common renal mutations and syndromes. We provide the first evidence of co-existence in the same organ and unequivocal relatedness of ESC-RCC, EVT, and LOT. End-stage renal disease was present in three of six patients with precursor lesions to all above tumors within adjacent renal parenchyma. In conclusion, identification of multifocal tumors with TSC-like morphology, especially in association with AMLs, could be the first manifestation of clinically silent TSC guiding clinical recommendations for further genetic testing and/or treatment recommendations.Molecular findings in ovarian, fallopian tube, and peritoneal high-grade serous carcinoma (HGSCa) are emerging as potential prognostic indicators. The chemotherapy response score (CRS) has been proposed as a histologic-based prognostic factor in patients with HGSCa treated with neoadjuvant chemotherapy (NACT). No study details the relationship between the mutational landscape of HGSCa and the CRS. This study addresses this issue using next-generation sequencing (NGS). We retrospectively identified 25 HGSCas treated with NACT and pathology material available to calculate the CRS. All cases had NGS on the primary debulking specimen post-NACT. The three-tier Böhm CRS was applied to the omentum or adnexa and calculated as a combined score. Tumor mutation burden (TMB) and TP53 variant allele frequency (VAF) were calculated and used in correlative analysis. All cases had at least one mutation, most commonly TP53 (25 cases, 100%). Other mutations were BRCA2 (one case, 4%), ARID1A (two cases, 8%), and 1 (4%) of each B showed no correlation with the CRS. TP53 VAF and average per cell TP53 mutational load showed significant correlation with the CRS, whether graded on the adnexa or omentum or as a combined score, indicating concordance between molecular and histological findings following NACT.The peripersonal space (PPS), the space surrounding us, is found to have enhanced multisensory-motor representation in the brain. In this study, we investigate how approaching sounds stopping at different distances within the peripersonal space, and carrying emotional content (positive, negative, and neutral), modulate the preparation of action as performing a Step. Premotor reaction times were measured by means of anticipatory forces and muscular activations to capture action preparation, the kinematics of stepping was considered for defining action performance, and for each stimulus, the individual perceived level of arousal and valence was evaluated. In general, we found a prompter premotor reaction for closer sounds compared to the farther ones and the fastest reactions detected for the neutral sound at each distance. We interpreted this time facilitation for neutral sound due to the large frequency spectrum of the stimuli and the absence of affective component and semantical content to decode. Interestingly, while at the close distance, none difference was found between positive and negative emotional stimuli, at the far distance faster reactions were present for negative compared to the positive sounds indicating that when arousal is less enhanced individuals are able to differentiate the emotional content of a sound. The kinematics observed after action initiation sustained the anticipatory results by showing that larger steps were performed when reacting to close compared to far sounds, being perceived as more arousing, and this happened particularly for neutral and negative sounds. Entinostat Altogether, the results showed that action preparation is influenced by the vicinity and by the valence carried by looming auditory stimuli. For discriminating the stimuli valence, a certain distance, still within the PPS, is necessary; when instead stimuli are too close to the body valence discrimination is not performed.