tumor atelectasis gives rise to a solid appearance in pulmonary adenocarcinomas on hr ct

Abstract Introduction Ground glass opacities on HR-CT scan, if malignant on histological examination, correlate with adenocarcinoma in situ. Solid appearance on HR-CT is often considered an invasive component. This study aims to compare radiological features on HR-CT and histological features of primary adenocarcinomas in resection specimens in order to demonstrate the presence of tumor atelectasis in ground glass nodules, part solid and solid nodules. Materials and Methods HR-CT imaging was evaluated, and lung nodules were classified as ground glass nodule, part solid nodule and solid nodule, while adenocarcinomas were classified according to WHO classification. Lepidic growth pattern with collapse was considered if reduction of air in the histological section was present, with maintained pulmonary architecture (without signs of pleural or vascular invasion). Results Radiological and histological features were compared in 47 lesions of 41 patients. The number of ground glass, part solid and solid nodules were 2, 8 and 37, respectively. Lepidic growth pattern with collapse was observed in both ground glass nodules, 7 out of 8 (88%) part solid and 24 out of 37 (65%) solid lesions. Remarkably, more than 50% of adenocarcinomas with solid appearance on HR-CT showed a pre-existing pulmonary architecture with adenocarcinoma with a predominant lepidic growth pattern. In these cases, the solid component can be explained by tumor related collapse in vivo (tumor atelectasis on radiology). Conclusion Tumor atelectasis is a frequent finding in pulmonary adenocarcinomas and results in solid appearance on HR-CT. A solid appearance on HR-CT can not only be attributed to invasion, as has been the assumption until now

Identification of protein biomarkers for prediction of response to platinum-based treatment regimens in patients with non-small cell lung cancer

The majority of patients with resected stage II-IIIA non-small cell lung cancer (NSCLC) are treated with platinum-based adjuvant chemotherapy (ACT) in a one-size-fits-all approach. However, a significant number of patients do not derive clinical benefit, and no predictive patient selection biomarker is currently available. Using mass spectrometry-based proteomics, we have profiled tumour resection material of 2 independent, multi-centre cohorts of in total 67 patients with NSCLC who underwent ACT. Unsupervised cluster analysis of both cohorts revealed a poor response/survival sub-cluster composed of ~ 25% of the patients, that displayed a strong epithelial-mesenchymal transition signature and stromal phenotype. Beyond this stromal sub-population, we identified and validated platinum response prediction biomarker candidates involved in pathways relevant to the mechanism of action of platinum drugs, such as DNA damage repair, as well as less anticipated processes such as those related to the regulation of actin cytoskeleton. Integration with pre-clinical proteomics data supported a role for several of these candidate proteins in platinum response prediction. Validation of one of the candidates (HMGB1) in a third independent patient cohort using immunohistochemistry highlights the potential of translating these proteomics results to clinical practice.</p

RNA isolation for transcriptomics of human and mouse small skin biopsies

<p>Abstract</p> <p>Background</p> <p>Isolation of RNA from skin biopsies presents a challenge, due to the tough nature of skin tissue and a high presence of RNases. As we lacked the dedicated equipment, i.e. homogenizer or bead-beater, needed for the available RNA from skin isolation methods, we adapted and tested our zebrafish single-embryo RNA-isolation protocol for RNA isolation from skin punch biopsies.</p> <p>Findings</p> <p>We tested our new RNA-isolation protocol in two experiments: a large-scale study with 97 human skin samples, and a small study with 16 mouse skin samples. Human skin was sampled with 4.0 mm biopsy punches and for the mouse skin different punch diameter sizes were tested; 1.0, 1.5, 2.0, and 2.5 mm. The average RNA yield in human samples was 1.5 μg with an average RNA quality RIN value of 8.1. For the mouse biopsies, the average RNA yield was 2.4 μg with an average RIN value of 7.5. For 96% of the human biopsies and 100% of the mouse biopsies we obtained enough high-quality RNA. The RNA samples were successfully tested in a transcriptomics analysis using the Affymetrix and Roche NimbleGen platforms.</p> <p>Conclusions</p> <p>Using our new RNA-isolation protocol, we were able to consistently isolate high-quality RNA, which is apt for further transcriptomics analysis. Furthermore, this method is already useable on biopsy material obtained with a punch diameter as small as 1.5 mm.</p

Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE trial

Contains fulltext : 87305.pdf (publisher's version ) (Open Access

The impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of predictive PD-L1 immunohistochemistry in lung cancer

OBJECTIVES: Programmed death-ligand 1 (PD-L1) is the only approved predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). However, predictive PD-L1 immunohistochemistry is subject to interobserver variability. We hypothesized that a pathologist's personality influences the interobserver variability and diagnostic accuracy of PD-L1 immunoscoring. MATERIALS AND METHODS: Seventeen pathologists performed PD-L1 immunoscoring on 50 resected NSCLC tumors in three categories (<1%;1-49%;≥50%). Also, the pathologists completed a certified personality test (NEO-PI-r), assessing five personality traits: neuroticism, extraversion, openness, altruism and conscientiousness. RESULTS: The overall agreement among pathologists for a series of 47 tumors was substantial (kappa = 0.63). Of these, 23/47 (49%) tumors were entirely negative or largely positive, resulting in a kappa value of 0.93. The remaining 24/47 (51%) tumors had a PD-L1 score around the cutoff value, generating a kappa value of 0.32. Pathologists with high scores for conscientiousness (careful, diligent) had the least interobserver variability (r = 0.6, p = 0.009). Also, they showed a trend towards higher sensitivity (74% vs. 68%, p = 0.4), specificity (86% vs. 82%, p = 0.3) and percent agreement (83% vs. 79%, p = 0.3), although not significant. In contrast, pathologists with high scores for neuroticism (sensitive, anxious) had significantly lower specificity (80% vs. 87%, p = 0.03) and percent agreement (78% vs. 85%, p = 0.03). Also, a trend towards high interobserver variability (r = -0.3, p = 0.2) and lower sensitivity (68% vs. 74%, p = 0.3) was observed, although not significant. Pathologists with relatively high scores for conscientiousness scored fewer tumors PD-L1 positive at the ≥ 1% cut-off (r = -0.5, p = 0.03). In contrast, pathologists with relatively high scores for neuroticism score more tumors PD-L1 positive at ≥ 1% (r = 0.6, p = 0.017) and ≥ 50% cut-offs (r = 0.6, p = 0.009). CONCLUSIONS: This study is the first to demonstrate the impact of a pathologist's personality on the interobserver variability and diagnostic accuracy of immunostaining, in the context of PD-L1 in NSCLC. Larger studies are needed for validation of these findings