[Non-small cell lung cancer in adults under 40 years of age]. / Cancers bronchiques non à petites cellules chez les adultes de moins de 40 ans : caractéristiques épidémiologiques, cliniques, histologiques et biologiques.

INTRODUCTION: Non-small cell lung cancers (NSCLC) are the most common lung cancers, withpeak incidence at 65years of age. These cancers rarely occur before the age of 40. METHODS: Based on an illustrative clinical case, a systematic review of the literature was conducted to study the epidemiological, clinical, histological, and biological characteristics of NSCLC in adults under 40years of age. Two equations were developed to search for articles on Medline and Scopus. RESULTS: Sixty-five articles were included in the review; 1.7% of patients were under 40years old, 50.7% were women, 66.7% presented adenocarcinoma, 51.9% were diagnosed at stage IV, 75% were non-smokers, 39.9% were exposed to other toxins, 33% had an EGFR mutation, 6.6% had a KRAS mutation, 25% had an ALK translocation, 73.7% were symptomatic, and over 75% had PS<2. CONCLUSION: NSCLC in patients under 40years of age presents characteristics different from those in older patients. Various factors are implicated, one example being lower exposure to tobacco, and they can influence the distribution of histological subtypes and the frequency of mutations.

Deferasirox's Anti-Chemoresistance and Anti-Metastatic Effect on Non-Small Cell Lung Carcinoma.

Clinically approved iron chelators, originally designed to address iron overload disorders, have emerged as potential anticancer agents. Deferasirox (Def), a tridentate iron chelator, has demonstrated antiproliferative effects in cancer. Background/Objectives: This study aims to elucidate the mechanism of action of Def and its impact on non-small cell lung carcinoma (NSCLC). Methods: NSCLC A549 cells were treated with Def to assess cytotoxicity, the effect on nuclear and mitochondrial pathways, and iron-containing proteins and genes to evaluate anti-metastasis and chemoresistance. A lung carcinoma mouse model was used for in vivo studies. Results: Our findings revealed that Def induced cytotoxicity, effectively chelated intracellular iron, and triggered apoptosis through the increase in phosphatidylserine externalization and caspase 3 activity. Additionally, Def caused G0/G1 cell cycle arrest by downregulating the ribonucleotide reductase catalytic subunit. Furthermore, Def perturbed mitochondrial function by promoting the production of reactive oxygen species and the inhibition of glutathione as a measurement of ferroptosis activation. Def demonstrated inhibitory effects on cell migration in scratch assays, which was supported by the upregulation of n-myc downstream-regulated gene 1 and downregulation of the epidermal growth factor receptor protein. Also, Def downregulated one of the main markers of chemoresistance, the ABCB1 gene. In vivo experiments using a lung carcinoma mouse model showed that Def treatment did not affect the animal's body weight and showed a significant decrease in tumor growth. Conclusions: This investigation lays the groundwork for unraveling Def action's molecular targets and mechanisms in lung carcinoma, particularly within iron-related pathways, pointing out its anti-metastasis and anti-chemoresistance effect.

Ovarian Cancer with TTF-1-positive Giant Pleural Dissemination.

Thyroid transcription factor 1 (TTF-1) is primarily expressed in lung and thyroid cancers, but it has also been observed in other cancers. A 60-year-old woman presented with worsening dyspnea, pleural effusion, lung metastases, a right ovarian tumor, and para-aortic intra-abdominal lymph node metastasis. Biopsies from the pleural dissemination revealed TTF-1-positive adenocarcinomas. To confirm the presence of the primary organ, biopsies were performed on a para-aortic intra-abdominal lymph node that ascended from the ovaries. An adenocarcinoma positive for TTF-1 was identified, thus confirming the diagnosis of ovarian cancer. Our findings revealed that TTF-1 positivity does not always signify a lung cancer origin.

Recommendation for Clinical T Staging in Patients with Non-Small Cell Lung Cancer: Volumetric Measurement: A Retrospective Study from Turkey.

Background: Currently, clinical T staging in non-small cell lung cancer (NSCLC) is based on the largest radiological diameter observed on computed tomography (CT). Under this system, tumors with varying shapes-such as spherical, amorphous, or spiculated tumors- can be assigned the same T stage even with different volumes. We aimed to propose a 3-dimensional (3D) volumetric staging system for NSCLC as an alternative to diameter-based T staging and to conduct comparative survival analyses between these methods. Methods: We retrospectively analyzed data from patients who underwent surgery for pT1-4N0M0 primary NSCLC between January 2018 and May 2022. Digital Imaging and Communications in Medicine data from patient CT scans were uploaded to 3D Slicer software for volumetric tumor measurement. Using the paired samples t-test or the Wilcoxon test, we compared the expected tumor volumes, calculated by tumor diameter, with the actual volumes measured by 3D Slicer. Receiver operating characteristic analysis was employed to determine the cut-off value for tumor volume. Kaplan-Meier analysis was utilized to assess overall survival, while the log-rank method was applied to compare survival differences between groups. The significance of changes in T stage was evaluated using the marginal homogeneity test. Results: The study included 136 patients. Significant differences were observed between expected and actual tumor volumes (p=0.01), and associated changes in T stage were also significant (p=0.04). The survival analysis performed using tumor volume (p=0.009) yielded superior results compared to that based on diameter (p=0.04) in paients with early tumor stage. Conclusion: T-factor staging based on tumor volume could represent an alternative staging method for NSCLC.

Software-assisted structured reporting and semi-automated TNM classification for NSCLC staging in a multicenter proof of concept study.

OBJECTIVES: In this multi-center study, we proposed a structured reporting (SR) framework for non-small cell lung cancer (NSCLC) and developed a software-assisted tool to automatically translate image-based findings and annotations into TNM classifications. The aim of this study was to validate the software-assisted SR tool for NSCLC, assess its potential clinical impact in a proof-of-concept study, and evaluate current reporting standards in participating institutions. METHODS: A framework for SR and staging of NSCLC was developed in a multi-center collaboration. SR annotations and descriptions were used to generate semi-automated TNM classification. The SR and TNM classification tools were evaluated by nine radiologists on n = 20 representative [18F]FDG PET/CT studies and compared to the free text reporting (FTR) strategy. Results were compared to a multidisciplinary team reference using a generalized linear mixed model (GLMM). Additionally, participants were surveyed on their experience with SR and TNM classification. RESULTS: Overall, GLMM analysis revealed that readers using SR were 1.707 (CI: 1.137-2.585) times more likely to correctly classify TNM status compared to FTR strategy (p = 0.01) resulting in increased overall TNM correctness in 71.9% (128/178) of cases compared to 62.8% (113/180) FTR. The primary source of variation in classification accuracy was explained by case complexity. Participants rated the potential impact of SR and semi-automated TNM classification as positive across all categories with improved scores after template validation. CONCLUSION: This multi-center study yielded an effective software-assisted SR framework for NSCLC. The SR and semi-automated classification tool improved TNM classification and were perceived as valuable. CRITICAL RELEVANCE STATEMENT: Software-assisted SR provides robust input for semi-automated rule-based TNM classification in non-small-cell lung carcinoma (NSCLC), improves TNM correctness compared to FTR, and was perceived as valuable by radiology physicians. KEY POINTS: SR and TNM classification are underutilized across participating centers for NSCLC staging. Software-assisted SR has emerged as a promising strategy for oncologic assessment. Software-assisted SR facilitates semi-automated TNM classification with improved staging accuracy compared to free-text reports in NSCLC.

Discrepancy Between Liquid Biopsy and Tumor Next-Generation Sequencing Due to Low Tumor Fraction in a Patient With Lung Adenocarcinoma.

Tumor next-generation sequencing (NGS) is the gold standard molecular testing for driver genomic alterations in patients with advanced non-small cell lung cancer (NSCLC). However, it requires a biopsy, which is an invasive procedure. In contrast, a liquid biopsy is a minimally invasive test that measures circulating tumor DNA (ctDNA) in the plasma and can be also used for molecular profiling. We report a case of a patient with stage IV metastatic lung adenocarcinoma with a negative liquid biopsy for tumor-derived genomic alterations but positive tissue NGS for mutations, including a driver KRASG12C mutation. The discrepancy between the two results can be attributed to low levels of ctDNA determined by tumor fraction below 1%, which prevents the liquid biopsy assay from detecting genomic alterations when the tumor shedding into the blood is below the detection threshold. It is well known in the literature that false negative liquid biopsies are possible, but a significant finding this case highlights is the clinical importance of tumor fraction in a liquid biopsy report. We conclude that patients with a liquid biopsy with low tumor fraction need further testing with tumor NGS to determine the presence of driver genomic alterations.

Rapidly worsening lung adenocarcinoma due to diffusely spreading lymphangitic carcinomatosis: A case report.

Lymphangitic carcinomatosis is a metastatic disease with a poor prognosis and poorly understood pathophysiology. We present a case of rapidly worsening lung adenocarcinoma with diffusely spreading cancerous lymphangitis in lung, mediastinum, retroperitoneum, and gastrointestinal tract. Our findings suggest cancer dissemination in this patient was predominantly caused by direct lymphatic invasion.

Deep learning to estimate response of concurrent chemoradiotherapy in non-small-cell lung carcinoma.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is a crucial treatment for non-small cell lung carcinoma (NSCLC). However, the use of deep learning (DL) models for predicting the response to CCRT in NSCLC remains unexplored. Therefore, we constructed a DL model for estimating the response to CCRT in NSCLC and explored the associated biological signaling pathways. METHODS: Overall, 229 patients with NSCLC were recruited from six hospitals. Based on contrast-enhanced computed tomography (CT) images, a three-dimensional ResNet50 algorithm was used to develop a model and validate the performance in predicting response and prognosis. An associated analysis was conducted on CT image visualization, RNA sequencing, and single-cell sequencing. RESULTS: The DL model exhibited favorable predictive performance, with an area under the curve of 0.86 (95% confidence interval [CI] 0.79-0·92) in the training cohort and 0.84 (95% CI 0.75-0.94) in the validation cohort. The DL model (low score vs. high score) was an independent predictive factor; it was significantly associated with progression-free survival and overall survival in both the training (hazard ratio [HR] = 0.54 [0.36-0.80], P = 0.002; 0.44 [0.28-0.68], P < 0.001) and validation cohorts (HR = 0.46 [0.24-0.88], P = 0.008; 0.30 [0.14-0.60], P < 0.001). The DL model was also positively related to the cell adhesion molecules, the P53 signaling pathway, and natural killer cell-mediated cytotoxicity. Single-cell analysis revealed that differentially expressed genes were enriched in different immune cells. CONCLUSION: The DL model demonstrated a strong predictive ability for determining the response in patients with NSCLC undergoing CCRT. Our findings contribute to understanding the potential biological mechanisms underlying treatment responses in these patients.

Diagnostic accuracy of CT and PET/CT radiomics in predicting lymph node metastasis in non-small cell lung cancer.

OBJECTIVES: This study evaluates the accuracy of radiomics in predicting lymph node metastasis in non-small cell lung cancer, which is crucial for patient management and prognosis. METHODS: Adhering to PRISMA and AMSTAR guidelines, we systematically reviewed literature from March 2012 to December 2023 using databases including PubMed, Web of Science, and Embase. Radiomics studies utilizing computed tomography (CT) and positron emission tomography (PET)/CT imaging were included. The quality of studies was appraised with QUADAS-2 and RQS tools, and the TRIPOD checklist assessed model transparency. Sensitivity, specificity, and AUC values were synthesized to determine diagnostic performance, with subgroup and sensitivity analyses probing heterogeneity and a Fagan plot evaluating clinical applicability. RESULTS: Our analysis incorporated 42 cohorts from 22 studies. CT-based radiomics demonstrated a sensitivity of 0.84 (95% CI: 0.79-0.88, p < 0.01) and specificity of 0.82 (95% CI: 0.75-0.87, p < 0.01), with an AUC of 0.90 (95% CI: 0.87-0.92), indicating no publication bias (p-value = 0.54 > 0.05). PET/CT radiomics showed a sensitivity of 0.82 (95% CI: 0.76-0.86, p < 0.01) and specificity of 0.86 (95% CI: 0.81-0.90, p < 0.01), with an AUC of 0.90 (95% CI: 0.87-0.93), with a slight publication bias (p-value = 0.03 < 0.05). Despite high clinical utility, subgroup analysis did not clarify heterogeneity sources, suggesting influences from possible factors like lymph node location and small subgroup sizes. CONCLUSIONS: Radiomics models show accuracy in predicting lung cancer lymph node metastasis, yet further validation with larger, multi-center studies is necessary. CLINICAL RELEVANCE STATEMENT: Radiomics models using CT and PET/CT imaging may improve the prediction of lung cancer lymph node metastasis, aiding personalized treatment strategies. RESEARCH REGISTRATION UNIQUE IDENTIFYING NUMBER (UIN): International Prospective Register of Systematic Reviews (PROSPERO), CRD42023494701. This study has been registered on the PROSPERO platform with a registration date of 18 December 2023. https://www.crd.york.ac.uk/prospero/ KEY POINTS: The study explores radiomics for lung cancer lymph node metastasis detection, impacting surgery and prognosis. Radiomics improves the accuracy of lymph node metastasis prediction in lung cancer. Radiomics can aid in the prediction of lymph node metastasis in lung cancer and personalized treatment.

Current status and quality of prognosis prediction models of non-small cell lung cancer constructed using computed tomography (CT)-based radiomics: a systematic review and radiomics quality score 2.0 assessment.

Background: Radiomics extracts specific quantitative data from medical images and explores the characteristics of tumors by analyzing these representations and making predictions. The purpose of this paper is to review computed tomography (CT)-based radiomics articles related to prognostic outcomes in non-small cell lung cancer (NSCLC), assess their scientificity and quality by the latest radiomics quality score (RQS) 2.0 scoring criteria, and provide references for subsequent related studies. Methods: CT-based radiomics studies on NSCLC prognosis published from 1 November 2012 to 30 November 2022 in English were screened through the databases of the Cochrane Library, Embase, and PubMed. By excluding criteria such as non-original studies, small sample sizes studies, positron emission tomography (PET)/CT only, and methodological studies only, 17 studies in English were included. The RQS proposed in 2017 is a quality evaluation index specific to radiomics following the PRISMA guidelines, and the latest update of RQS 2.0 has improved the scientificity and completeness of the score. Each checkpoint either belongs to handcrafted radiomics (HCR), deep learning, or both. Results: The 17 included studies covered most treatments for NSCLC, including radiotherapy, chemotherapy, surgery, radiofrequency ablation, immunotherapy, and targeted therapy, and predicted outcomes such as overall survival (OS), progression-free survival (PFS), distant metastases, and disease-free survival (DFS). The median score rate for the included studies was 28%, with a range of 12% to 44%. The quality of studies in HCR is not high, and only 4 studies have been validated with independent cohorts. Conclusions: The value of radiomics studies needs to be increased, such that clinical application will be possible, and the field of radiomics still has much room for growth. To make prediction models more reliable and stable in forecasting the prognosis of NSCLC and advancing the individualized treatment of NSCLC patients, more clinicians must participate in their development and clinical testing.

Are 19del and L858R really different disease entities?

Clinicians have recognized the similarities and differences between the two subtypes of common epidermal growth factor receptor (EGFR) mutations, but actual treatment strategies have not yet changed. The L858R mutation can be understood by considering the pharmacological conformational plasticity of the receptor protein and the presence of other co-occurring mutations, whether subtypes of EGFR or non-EGFR mutations and differences in downstream signaling pathways. As long as we know that molecular differences lead to biological differences, it is a challenge for all of us that our treatment strategies must change.

[Box: see text].

Tetraspanin 3 promotes NSCLC cell proliferation via regulation of ß1 integrin intracellular recycling.

BACKGROUND: The involvement of tetraspanins in cancer development has been widely implicated. In this study, the function and molecular mechanisms of tetraspanin 3 (TSPAN3) in non-small cell lung cancer (NSCLC) cells were explored. METHODS: Tissue samples from patients diagnosed with NSCLC were analyzed by immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) to indicate the involvement of TSPAN3 in cancer progression. In the meantime, we also performed exhaustive mechanistic studies using A549 and H460 cells in vitro through a variety of methods including western blotting, real-time PCR, immunofluorescent staining, coimmunoprecipitation, cell proliferation assay, and nocodazole (NZ) washout assay. Proper statistical analysis was implemented wherever necessary in this study. RESULTS: TSPAN3 was found to be highly expressed in lung cancer cells and tissues. Moreover, high levels of TSPAN3 positively correlated with poor differentiation, lymph node involvement, advanced pathological tumor-node-metastasis stage, and poor prognosis in patients with NSCLC. TSPAN3 showed potential to promote the proliferation of NSCLC cells in vitro and in vivo. Specifically, TSPAN3 was found to interact with ß1 integrin via the LEL domain, thereby facilitating the sorting of ß1 integrin into Rab11a endosomes and promoting ß1 integrin recycling and upregulation. CONCLUSIONS: Our findings reveal TSPAN3 may represent a potentially valuable therapeutic target for NSCLC.

Incorporation of whole-body metabolic tumor burden into current prognostic models for non-small cell lung cancer patients with spine metastasis.

BACKGROUND CONTEXT: Numerous prognostic models are utilized for surgical decision and prognostication in metastatic spine tumors. However, these models often fail to consider the whole-body tumor burden into account, which may be crucial for the prognosis of metastatic cancers. A potential surrogate marker for tumor burden, whole-body metabolic tumor burden (wMTB), can be calculated from total lesion glycolysis (TLG) obtained from 18F-Fludeoxyglucose positive emission tomography (18F-FDG PET) images. PURPOSE: We aimed to improve prognostic power of current models by incorporating wMTB for non-small cell lung cancer (NSCLC) patients with spine metastases. DESIGN: Retrospective analysis using a review of electrical medical records and survival data. PATIENT SAMPLE: In this study, we included 74 NSCLC patients with image proven spine metastases. OUTCOME MEASURES: Increase in Integrated Discrimination Improvement (IDI) index after incorporation of wMTB into prognostic scores. METHODS: Enrolled patients' baseline data, cancer characteristics and survival status were retrospectively collected. Five widely used prognostic scores (Tomita, Katagiri, Tokuhashi, Global Spine Tumor Study Group [GSTSG], New England Spine Metastasis Score [NESMS]), and TLG indexes were calculated for all patients. The relationships among survival time, prognostic models and TLG values were analyzed. Improvement of prognostic power was validated by incorporating significant TLG index into significant current models. RESULTS: Among current prognostic models, Tomita (EGFR wild-type), Katagiri, GSTSG and Tokuhashi were significantly related to patient survival. Among TLG indexes, LogTLG3 was significantly related to survival. Incorporation of LogTLG3 into significant prognostic models resulted in positive IDI index until 3 years in all models. CONCLUSION: This study showed that incorporation of wMTB improved prognostic power of current prognostic models of metastatic spine tumors.

Real-world overall survival after alternative dosing for pembrolizumab in the treatment of non-small cell lung cancer: A nationwide retrospective cohort study with a non-inferiority primary objective.

BACKGROUND: High and increasing expenses on pembrolizumab ask for more cost-effective and sustainable treatment strategies to improve affordability of healthcare. Therefore, a part of the Dutch hospitals implemented an alternative, partially lower, weight-based dosing protocol for pembrolizumab. This provided the unique opportunity to compare the overall survival (OS) of the alternative pembrolizumab dosing protocol to standard dosing using a nationwide registry in non-small cell lung cancer (NSCLC) patients. METHODS: This is a retrospective cohort study with a non-inferiority primary objective. Forty hospitals in the Dutch Medication Audit and Dutch Lung Cancer Audit treated 1966 patients with NSCLC with first line pembrolizumab (mono- or combination therapy) between Jan 1st 2021, and Mar 31st, 2023. Alternative weight-based pembrolizumab dosing (100/150/200 mg Q3W or 200/300/400 mg Q6W) was administered to 604 patients, and 1362 patients received standard pembrolizumab dosing (200 mg Q3W or 400 mg Q6W). A Cox proportional hazard model with selected covariates was used to compare the OS between alternative and standard dosing protocols. The non-inferiority margin was set at a hazard ratio (HR) of 1.2 for OS. Non-inferiority is established by showing that the upper limit of the 95 % confidence interval (CI) of the HR of OS is smaller or equal to 1.2. RESULTS: Distribution of age (66.7 years +/-9.4), sex (45 % female) and treatment combinations were similar for both groups, comorbidity score was higher in the standard group. Median daily dose in the alternative dosing group was 22 % lower compared to the standard dosing group, 7.14 mg/day (interquartile range (IQR):5.48-8.04 mg/day) vs. 9.15 mg/day (IQR:8.33-9.52 mg/day), respectively. Alternative dosing was non-inferior to standard dosing regarding overall survival (adjusted HR 0.83, 95 %CI:0.69-1.003). CONCLUSION: This large, retrospective real-world analysis supports the hypothesis that the alternative, partially lower pembrolizumab dosing protocol in NSCLC maintains treatment effectiveness while reducing treatment costs.

Five-year outcomes with first-line nivolumab plus ipilimumab with 2 cycles of chemotherapy versus 4 cycles of chemotherapy alone in patients with metastatic non-small cell lung cancer in the randomized CheckMate 9LA trial.

BACKGROUND: We report 5-year efficacy and safety outcomes from CheckMate 9LA in patients with metastatic non-small cell lung cancer (mNSCLC) and exploratory analyses in key patient subgroups. METHODS: Adults with stage IV/recurrent NSCLC and no sensitizing EGFR/ALK alterations were randomized to receive nivolumab plus ipilimumab with chemotherapy (n = 361) or chemotherapy (n = 358). Outcomes were assessed in all randomized patients and subgroups. RESULTS: With 57.3 months' minimum follow-up, patients continued to derive overall survival (OS) benefit with nivolumab plus ipilimumab with chemotherapy over chemotherapy (HR, 0.73; 95% CI, 0.62-0.85; 5-year OS rates, 18% vs. 11%), regardless of tumor programmed death ligand 1 (PD-L1) expression (PD-L1 < 1%, 22% vs. 8%; PD-L1 ≥ 1%, 18% vs. 11%), histology (squamous, 18% vs. 7%; non-squamous, 19% vs. 12%), or presence of baseline brain metastases (20% vs. 6%). Five-year duration of response (DOR) rates were 19% versus 8% with nivolumab plus ipilimumab with chemotherapy versus chemotherapy, with consistent benefit across subgroups. Patients who discontinued nivolumab plus ipilimumab with chemotherapy due to treatment-related adverse events had a 5-year OS rate of 37%. Five-year progression-free survival and DOR rates in 5-year survivors were 55% versus 38% and 59% versus 46%, respectively. No new safety signals were observed in 5-year survivors, regardless of the number of ipilimumab doses received. CONCLUSION: This 5-year update supports the long-term, durable OS benefit and improved 5-year survivorship with nivolumab plus ipilimumab with chemotherapy over chemotherapy in patients with mNSCLC, regardless of tumor PD-L1 expression or histology. GOV REGISTRATION: NCT03215706.

Epidermal growth factor receptor-mutated lung carcinomas with insufficient response to epidermal growth factor receptor inhibitors.

Administration of single-agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a standard treatment option for metastatic non-small cell lung carcinomas with EGFR exon 19 deletions (ex19del) and L858R substitutions. However, there is a significant interpatient heterogeneity with regard to the degree of the response and its duration. Patients with EGFR ex19del mutation, TP53 wild-type, good performance status, low tumor burden and no circulating tumor DNA (ctDNA) at baseline have the best chances to derive pronounced benefit from TKI therapy. In contrast, subjects with EGFR L858R substitution, mutated TP53, poor overall condition, high tumor volume and detectable ctDNA are generally poor responders to EGFR inhibitors. ctDNA dynamics in the first days or weeks of treatment allows reliable identification of patients, who are very unlikely to derive clinically meaningful benefit from single-agent TKIs. These patients are candidates for clinical trials, which may involve the addition of chemotherapy and antiangiogenic drugs to patients, who failed to achieve immediate benefit from TKI monotherapy.

[Box: see text].

Correlation between Periostin Expression and Pro-Angiogenic Factors in Non-Small-Cell Lung Carcinoma.

The role of periostin (POSTN) in remodeling the microenvironment surrounding solid tumors and its effect on the tumor cells in non-small-cell lung carcinoma (NSCLC) have not yet been fully understood. The aim of this study was to determine the relationship between POSTN expression (in tumor cells [NSCLC cells] and the tumor stroma) and pro-angiogenic factors (CD31, CD34, CD105, and VEGF-A) and microvascular density (MVD) in NSCLC. In addition, these associations were analyzed in individual histological subtypes of NSCLC (SCC, AC, and LCC) and their correlations with clinicopathological factors and prognosis were examined. Immunohistochemistry using tissue microarrays (TMAs) was used to assess the expression of POSTN (in tumor cells and cancer-associated fibroblasts [CAFs]) and the pro-angiogenic factors. A significant positive correlation was found between the expression of POSTN (in cancer cells/CAFs) and the expression of the analyzed pro-angiogenic factors (CD31, CD34, CD105, and VEGF-A) and MVD in the entire population of patients with NSCLC and individual histological subtypes (AC, SCC). In addition, this study found that POSTN expression (in tumor cells/CAFs) increased with tumor size (pT), histopathological grade (G), and lymph-node involvement (pN). In addition, a high expression of POSTN (in tumor cells and CAFs) was associated with shorter survival among patients with NSCLC. In conclusion, a high expression of POSTN (in cancer cells and CAFs) may be crucial for angiogenesis and NSCLC progression and can constitute an independent prognostic factor for NSCLC.

Cytomorphological Features as a Subtyping Tool of Non-Small-Cell Lung Cancer in Brushing Bronchoscopic Samples.

Background and Objective: Nowadays, the separation of adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) is crucial given that there are new specific targeted therapies. So, the aim of this study was to examine the differences in cytomorphological features between ADC and SCC in bronchoscopic brush samples. Material and Methods: The retrospective study was conducted over a 3-year period at Western Balkan University Hospital. All brushing samples were analysed. According to the histopathological report, patients were classified into ADC and SCC groups. The cytomorphological features analysed in 95 samples were presence of necrosis, cell distribution, nuclear atypia, size of nuclei, and visibility of nucleoli. Statistical analysis was performed in JASP, and P values <0.05 were considered significant. Results: The necrotic background was more frequent in SCC samples. Small clusters sized ≤200 µm were found in 17.95% of samples from the SCC group and 53.57% in the ADC group. Large clusters sized >400 µm were found in 43.59% in the SCC group, while in the ADC group, it was found in 5.36%. There were no differences in nuclear atypia between groups. Nuclei that were >5x lymphocyte size were found more often in samples from ADC than in the SCC group (37.50 vs 10.25%). In 89.75% of samples from the SCC group, nuclei were ≤5x lymphocyte sizes, while in the ADC group, the percentage was 63.5%. Nucleoli were more often visible in samples from the ADC group compared to the SCC group (92.86% vs 64.10%, P < 0,05). Conclusions: Small clusters, large nuclei, and visible nucleoli were more frequent in the ADC group (P < 0.05), while large clusters, small nuclei, and invisible nucleoli were more frequent in the SCC group (P < 0.05).

Methodological and TNM Focus-Based Comparison of EGFR Mutation Status in Non-Small-Cell Lung Carcinomas.

Background: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung carcinomas (NSCLC) are a frequent class of driver mutations, and tyrosine kinase inhibitor (TKI) therapy provides considerable clinical benefits. Using the most effective and also easiest method for EGFR analysis is cost-effective and time-saving. In this study, we aimed to determine which method could be more effective by comparing the incidences of EGFR mutations in cytological and histological samples which were obtained by different methods also, whether there was a difference in the incidences of EGFR mutations between the primary foci, mediastinal lymph nodes, and distant metastatic foci. Materials and Methods: We retrospectively reviewed 420 cases of cytological materials, small biopsies, and surgical samples reported as NSCLC underwent EGFR analysis in our department between 2016 and 2022. We collected the data and interpreted the results from two different perspectives. Results: We identified 36 EGFR mutations in 362 biopsies (9.94%) and 17 in 58 cytology samples (29.31%). There is a significant difference between the two methods (P = 0.01*). We observed 38 EGFR mutations in 320 primary foci (11.87%), 7 EGFR mutations in 36 mediastinal or subcarinal lymph nodes (19.44%), and 8 EGFR mutations in 64 distant metastatic foci (12.50%). A significant difference was also observed in pleural samples (P = 0.005*). Conclusion: We observed more successful results with cell blocks obtained from liquid-based cytological specimens than with formalin-fixed, paraffin-embedded tissues obtained from resection or otherwise in our clinical routine. Our study results highlight the benefits of cytological specimens in molecular treatments and current therapy modalities.

Corrigendum: Proteasome inhibitor YSY01A abrogates constitutive STAT3 signaling via down-regulation of Gp130 and JAK2 in human A549 lung cancer cells.

[This corrects the article DOI: 10.3389/fphar.2017.00476.].