Background As Immune checkpoint inhibitors (ICPIs) are changing the standard-care in lung cancer with good clinical activities and durable responses, its indication must be based on the appropriate patient selection once only a fraction of patients has a response to these costly drugs. In larger cohorts the expression of programmed cell death–ligand 1 (PD-L1) has been associated with good clinical response of ICPIs in lung adenocarcinoma where the rate of high PD-L1 expression (defined as PD-L1tumor proportion score ≥ 50%) is ~ 30%, but once rare studies are available addressing the frequency of PD-L1 in populations outside those cohorts, we aimed to report the prevalence of PD-L1 and the frequency of patients with high PD-L1 expression utilizing data from a major pathology laboratory in Northeastern Brazil. Methods We retrospectively evaluated the PD-L1 expression in 158 surgically resected primary lung adenocarcinoma including 158 with anaplastic lymphoma kinase (ALK) expression. PD-L1 and ALK expression were evaluated by immunohistochemical analysis with the SP263 and D5F3 assays, respectively. Results Of the 158 samples analyzed, 94 (59.5%) had a PD-L1 tumor proportion score (TPS) < 1%, 38 (24.0%) had a PD-L1 TPS of 1–49% and 26 (16.5%) had a PD-L1 TPS of ≥50%. ALK expression was detected in 21 (13.3%) of the 158 tumor samples and 5 (3.2%) of them had a PD-L1 TPS of ≥50%. Conclusion The frequency of strong PD-L1 expression was lower than that previously reported in the trials where PD-L1 expression was used as a biomarker for patient selection. Also, considering that a subset of patients with ALK positivity had a strong PD-L1 expression, further studies will be required to examine the efficacy of PD-1/PD-L1 inhibitors in such patients.

Objective: To investigate the histological subtypes and mutational profiles of non-small cell lung cancer in Brazil, looking for correlations among histological subtypes, expression of anaplastic lymphoma kinase (ALK), EGFR mutation status, and programmed death-ligand 1 (PD-L1) expression. Methods: We evaluated 173 specimens obtained from patients with lung adenocarcinoma in northeastern Brazil. Expression of PD-L1 and ALK was evaluated by immunohistochemistry; EGFR mutation status was evaluated by sequencing. We categorized the histological subtypes in accordance with the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Results: The most common histological subtypes of lung adenocarcinoma were solid predominant (in 46.8%), acinar predominant (in 37.0%), and lepidic predominant (in 9.8%). ALK expression was detected in 10.4% of the samples, and 22.0% of the tumors harbored EGFR mutations. The most common EGFR mutation was an exon 21 L858R point mutation (in 45.5%), followed by an exon 19 deletion (in 36.3%). The tumor proportion score for PD-L1 expression was ≥ 50% in 18.2% of the samples, 1-49% in 32.7%, and 0% in 49.5%. The solid predominant subtype was significantly associated with wild-type EGFR status (p = 0.047). Positivity for PD-L1 expression was not found to be significantly associated with ALK expression or EGFR mutation status. Conclusions: Our results suggest that the molecular profile of non-small cell lung cancer in northeastern Brazil differs from those of populations in other regions of the country, with ALK positivity being higher than the other biomarkers. Further studies including clinical and genetic information are required to confirm these differences, as well as studies focusing on populations living in different areas of the country.

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BackgroundGlycogen Synthase Kinase-3 beta (GSK-3β) regulates diverse cell functions including metabolic activity, signaling and structural proteins. GSK-3β phosphorylates target pro-oncogenes and regulates programmed cell death-ligand 1 (PD-L1). This study investigated the correlation between GSK-3β expression and clinically relevant molecular features of lung adenocarcinoma (PDL1 score, PTEN expression and driver mutations).MethodsWe evaluated 95 lung cancer specimens from biopsies and surgical resections. Immunohistochemistry was performed to analyze the expression of GSK-3β, PTEN, and PDL1. Epidemiological data, molecular characteristics and staging were evaluated from medical records. The histologic classification was performed by an experienced pulmonary pathologist.ResultsMost patients were female (52.6%) and the majority had a positive smoking history. The median age was 68.3 years, with individuals over 60 years accounting for 82.1%. The predominant histological subtype was adenocarcinoma (69.5%), followed by squamous cell carcinoma (20.0%). GSK-3β expression in tumors was cytoplasmic with a dotted pattern and perinuclear concentration, with associated membranous staining. Seven (7.3%) tumors had associated nuclear expression localization. Seventy-seven patients (81.1%) had advanced clinical-stage tumors. GSK-3β was positive in 75 tumors (78%) and GSK3-positive tumors tended to be diagnosed at advanced stages. Among stage III/IV tumors, 84% showed GSK3 positivity (p= 0.007). We identified a statistically significant association between GSK-3β and PTEN in the qualitative analysis (p 0.021); and when comparing PTEN to GSK-3β intensity 2+ (p 0.001) or 3+ expression (&gt; 50%) – p 0.013. GSK-3β positive tumors with a high histological score had a worse overall survival.ConclusionWe identified the histological patterns of GSK-3β expression and evaluated its potential as marker for overall survival, establishing a simple histological score to measure the evaluated status in resected tissues. The use of GSK-3β expression as an immune response biomarker remains a challenge. Future studies will seek to explain the role of its interaction with PTEN.

Purpose To develop and validate a chest cavity simulator for teaching video-assited thoracic surgery (VATS). Methods The first phase of the study consisted of developing a chest cavity simulator. A quasi-experimental study was performed in the second phase, and 25 surgeons and residents participated in a three-stage pulmonary suture experiment. The videos were recorded and timed. Generalized linear regression models for repeated measures were used to analyze the outcome change over time. Results The chest cavity simulator consists of a console simulating the left hemithorax. Among the participants, 96% rated the design, visual aspect, positioning ergonomics, and triangulation of the portals as very good or excellent (face validity). There was a decrease in suturing time in step 1 from 435.7 ± 105 to 355.6 ± 76.8 seconds compared to step 3 (p = 0.001). The evaluation of the simulation effectiveness and performance (content validity) was rated as very good or excellent by 96% ofparticipants. The most experienced surgeon showed significant reduction in procedure time (p = 0.021) (construct validity). Conclusions The thoracic cavity simulator is realistic, showing content and construct validity, and can be used in VATS training. The simulation model allowed skill gain in the endoscopic suture.