Lobectomy is the standard surgical approach for early-stage non-small cell lung cancer (NSCLC), while segmentectomy has gained increasing attention as a parenchyma-sparing alternative. Recent randomized prospective trials have demonstrated comparable survival outcomes between the two procedures in patients with peripherally located, node-negative NSCLC ≤ 2 cm. This study aimed to compare survival outcomes between segmentectomy and lobectomy in patients with T1N0 NSCLC. We conducted a retrospective, multicenter study using data from six thoracic surgery clinics across Türkiye. Initially, 317 patients who underwent segmentectomy and 252 who underwent lobectomy were identified. After 1:1 propensity score matching with a 20

Background:Single-port (SP) robotic platforms aim to reduce surgical trauma by allowing all instruments through a single incision. In thoracic surgery, SP experience has been reported mainly via subxiphoid or subcostal routes, whereas the intercostal approach and heterogeneous case series remain scarce. We report an initial technical feasibility experience with intercostal SP robotic thoracic surgery, the first reported from Turkey. Methods:This single-center retrospective review included the first 10 consecutive patients who underwent thoracic surgery with the da Vinci SP Surgical System via a standardized intercostal approach (single 2-4 cm incision at the midaxillary line, approximately the sixth intercostal space; March 13-April 28, 2026). Procedures comprised anatomic and wedge lung resections, esophageal surgery, and mediastinal/paraesophageal mass excision. This is presented as an initial technical experience rather than a comparative outcomes study; the primary endpoint was technical feasibility. Results:Ten patients (seven women and three men; mean age: 57 years, range: 44-68) underwent pulmonary resection (n = 5), esophageal surgery (n = 3), and mediastinal/paraesophageal mass excision (n = 2). All procedures were completed through a single intercostal incision, with no additional incision, no conversion, and no instrument clash. Mean operative time was 48.6 minutes (pulmonary/mediastinal) and 67 minutes (thoracic phase and esophageal); mean docking time was 4.4 minutes. Mean blood loss was 68 ± 32 mL, mean chest tube duration was 2.2 ± 1.3 days, and mean length of stay was 2.8 ± 1.4 days. Four patients underwent synchronous SP abdominal procedures. No complications, reinterventions, or 30-day mortality occurred. Conclusion:In this small, highly selected initial series performed by an experienced team, intercostal SP robotic thoracic surgery appeared technically feasible across a range of thoracic procedures. Given the limited sample size and retrospective design, these findings should be regarded as hypothesis-generating; larger prospective studies are needed before conclusions regarding safety or comparative outcomes can be drawn.

Purpose/Objective: To evaluate the safety and failure patterns of consolidative hypofractionated thoracic radiotherapy (RT) following induction chemoimmunotherapy in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). Materials/Methods: This retrospective study included 34 patients treated between 2019 and 2025. All patients received induction chemoimmunotherapy followed by consolidative hypofractionated RT based on multidisciplinary tumor board recommendations. The primary endpoint was local recurrence (LR); secondary endpoints were regional recurrence (RR), distant metastasis (DM), overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. Results: Median age was 64 years, and median PD-L1 expression was 20%. Most patients had stage III disease; squamous cell carcinoma (56%) and adenocarcinoma (38%) were the predominant histologies. The most common systemic regimen was carboplatin/paclitaxel plus nivolumab, with a median of four induction cycles. Post-induction response was complete in 21%, partial in 62%, stable in 12%, and progressive in 6%. Median RT dose was 52.5 Gy in 15 fractions, and maintenance immunotherapy was administered in 79%. At a median follow-up of 16.7 months, using cumulative incidence functions with death treated as a competing event, the 1- and 2-year cumulative incidences of local failure were 6.9% and 14.7%, respectively. The corresponding cumulative incidences of regional failure were 10.2% and 18.8%, while distant metastasis incidences were 15.9% and 39.2%. No isolated local or regional recurrences occurred. One- and two-year OS rates were 86% and 81%, and corresponding PFS rates were 76% and 54%. No grade 4-5 RT-related toxicity occurred; one grade 5 immune-related pneumonitis was observed. Conclusions: Consolidative hypofractionated RT following chemoimmunotherapy appears feasible and associated with favorable outcomes, supporting further prospective investigation.

e20053 Background: Recurrence risk after curative-intent surgery in early-stage (I–II) NSCLC remains heterogeneous. We developed and externally validated a machine-learning model to improve recurrence risk stratification for personalized postoperative management. Methods: We retrospectively evaluated a cohort of 724 patients with stage I–II NSCLC who underwent curative-intent resection. Recurrence was defined as radiologic and/or pathologic evidence of relapse, and a total of 52 patients experienced disease recurrence. A Random Forest (RF) classifier was trained using 11 routinely collected variables and benchmarked against Logistic Regression (LR) within a nested cross-validation pipeline to prevent data leakage. MICE imputation was performed strictly within the cross-validation folds. The independent external cohort (n = 50) was intentionally enriched (25 recurrence/25 no recurrence) to enable stable discrimination testing. Clinical utility was assessed via Decision Curve Analysis (DCA), and interpretability was established using SHapley Additive exPlanations (SHAP). Results: Median follow-up was 4.2 years. The Random Forest model outperformed Logistic Regression in both internal (ROC-AUC 0.704 vs 0.64) and external validation (ROC-AUC 0.71 vs 0.57). In internal out-of-fold analysis, the RF model achieved a sensitivity of 73.1% and specificity of 63.5% at a Youden-optimal threshold of 0.41. External validation demonstrated a consistent ROC-AUC of 0.71 (95% CI: 0.56–0.85). SHAP analysis identified tumor size, FEV1/FVC ratio, STAS, T-stage, and necrosis as the most influential predictors of recurrence. DCA showed superior net clinical benefit compared to "treat-all" or "treat-none" strategies. Conclusions: Our interpretable Random Forest model demonstrates stable discrimination and external validation using standard clinical data. This approach may support risk-adapted surveillance and guide postoperative decision-making, warranting prospective multicenter validation.

Background/Objectives: Despite advances in the TNM staging system, prognostic heterogeneity persists in early-stage non-small cell lung cancer (NSCLC). Lymphatic invasion (LI) is a known marker of aggression, but its independent significance in the critical, low-risk Stage I, N0 subgroup-typically ineligible for adjuvant therapy-remains poorly defined. We hypothesized that LI acts as a powerful, yet hidden, risk factor in this highly favourable cohort. Methods: This retrospective cohort study included 988 consecutive patients who underwent curative anatomical resection for NSCLC. All patients underwent complete resection with pathologically confirmed negative surgical margins (R0 resection). Cases were staged according to the 9th Edition of the TNM Classification of Malignant Tumours (TNM-9) and grouped as LI-positive or LI-negative. A critical subgroup analysis focused on 347 truly low-risk patients (TNM Stage I, N0, no vascular or pleural invasion). Overall survival (OS) was evaluated using the Kaplan-Meier method and multivariable Cox proportional hazards models. Results: In the entire cohort (n = 988), LI was present in 40.9% of cases. LI positivity was an independent predictor of worse OS in multivariable analysis (HR: 1.520, 95% CI: 1.004-2.301, p = 0.048). In the low-risk subgroup (n = 347), the presence of LI resulted in a drastic survival divergence, with 5-year OS declining from 96.1% (LI-negative) to 83.8% (LI-positive). Multivariable analysis confirmed LI as an independent adverse prognostic factor in this subgroup (HR: 4.002, 95% CI: 1.567-10.221, p = 0.004). Conclusions: Lymphatic invasion is a robust, independent adverse prognostic factor in resected NSCLC. LI may identify a subset of early-stage N0 NSCLC patients who warrant closer postoperative surveillance and prospective evaluation for adjuvant treatment strategies. Validation in prospective cohorts is required before LI can be formally integrated into staging algorithms or treatment guidelines.

INTRODUCTION:The standard concurrent chemoradiotherapy (c-CT) regimen for limited-stage small cell lung cancer (LS-SCLC) has historically been 45 Gy in 30 twice-daily (BID) fractions. Recent findings by Yu et al. suggest that dose escalation up to 54 Gy may improve overall survival (OS) without increasing toxicity. However, real-world evidence on the safety and efficacy of dose escalation using modern radiotherapy techniques remains limited. This study aimed to evaluate survival outcomes and treatment tolerability in LS-SCLC patients treated with dose-escalated BID radiotherapy using the simultaneous integrated boost (SIB) technique. MATERIALS AND METHODS:Patients with LS-SCLC who received c-CT and BID radiotherapy with SIB-based dose escalation (54Gy/30fr) were retrospectively analyzed. All treatment planning was performed with Intensity-Modulated Radition Therapy using heterogeneity correction after 4D-CT simulation. The primary endpoint was OS; secondary endpoints included disease-free survival (DFS) and treatment-related toxicities. RESULTS:From March 2010 to December 2024, 66 patients were included. Median age was 65 years, with a median follow-up of 31 months. Median OS was 53 months and median DFS 18 months. Grade 3 acute esophagitis occurred in 7.6%, and grade 3 pneumonitis in 3%. No grade ≥4 toxicities were observed. No grade ≥4 toxicities were reported. CONCLUSION:Dose-escalated BID radiotherapy using SIB was effective and well tolerated, yielding favorable local control. However, distant metastases remained the predominant failure pattern, limiting the OS benefit compared with the 62.4 months reported by Yu et al. Interpretation should consider the retrospective design, treatment heterogeneity over a decade, and potential selection biases.

Tumor extracellular matrices (ECM) exhibit aberrant changes in composition and mechanics compared to normal tissues. Proteoglycans (PG) are vital regulators of cellular signaling in the ECM with the ability to modulate receptor tyrosine kinase (RTK) activation via their sulfated glycosaminoglycan (sGAG) side chains. However, their role on tumor cell behavior is controversial. Here, it is demonstrated that PGs are heavily expressed in lung adenocarcinoma (LUAD) patients in correlation with invasive phenotype and poor prognosis. A bioengineered human lung tumor model that recapitulates the increase of sGAGs in tumors in an organotypic matrix with independent control of stiffness, viscoelasticity, ligand density, and porosity, is developed. This model reveals that increased sulfation stimulates extensive proliferation, epithelial-mesenchymal transition (EMT), and stemness in cancer cells. The focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K) signaling axis is identified as a mediator of sulfation-induced molecular changes in cells upon activation of a distinct set of RTKs within tumor-mimetic hydrogels. The study shows that the transcriptomic landscape of tumor cells in response to increased sulfation resembles native PG-rich patient tumors by employing integrative omics and network modeling approaches.

This study examines the effects of the bundle of antimicrobial stewardship measures for prophylactic antibiotics among thoracic surgery patients. A local protocol, based on current guidelines starting from December 2014, was developed by the Infection Control and Thoracic Surgery Teams. The effects of this protocol were assessed by monitoring a total of 1380 patients before and after its implementation from January 1, 2011, to December 31, 2022.

Extracellular matrix (ECM)-derived hydrogels are in demand for use in lung tissue engineering to mimic the native microenvironment of cells in vitro. Decellularization of native tissues has been pursued for preserving organotypic ECM while eliminating cellular content and reconstitution into scaffolds which allows re-cellularization for modeling homeostasis, regeneration, or diseases. Achieving mechanical stability and understanding the effects of the decellularization process on mechanical parameters of the reconstituted ECM hydrogels present a challenge in the field. Stiffness and viscoelasticity are important characteristics of tissue mechanics that regulate crucial cellular processes and their in vitro representation in engineered models is a current aspiration. The effect of decellularization on viscoelastic properties of resulting ECM hydrogels has not yet been addressed. The aim of this study was to establish bovine lung tissue decellularization for the first time via pursuing four different protocols and characterization of reconstituted decellularized lung ECM hydrogels for biochemical and mechanical properties. Our data reveal that bovine lungs provide a reproducible alternative to human lungs for disease modeling with optimal retention of ECM components upon decellularization. We demonstrate that the decellularization method significantly affects ECM content, stiffness, and viscoelastic properties of resulting hydrogels. Lastly, we examined the impact of these aspects on viability, morphology, and growth of lung cancer cells, healthy bronchial epithelial cells, and patient-derived lung organoids.

BACKGROUND:Lung cancer is known as the most common and highly metastatic form of cancer worldwide. Tumour node metastasis (TNM) staging is the gold standard classification system for the decision-making process for appropriate treatment. Particularly N status has the most important prognostic value in the absence of distant metastasis. Traditional diagnostic methods are capable of detecting metastasis; however, they may fail to detect micrometastasis, which plays a role in disease recurrence and patients' long-term survival. Occult micrometastasis can change the tumour's TNM staging and, consequently, the patient's treatment regimen.METHODS:The median number of three lymph node tissues were collected from 30 patients who underwent surgery for non-small cell lung cancer. Lymph node tissues were collected from different lymph node stations according to the location of the patient's tumour. CK19, EpCAM and CEACAM5 gene expressions were analysed in tissues using quantitative real-time polymerase chain reaction to detect micrometastasis in distant lymph nodes.RESULTS:Triple positivity was seen in 26 out of 30 patients which 19 patients were upstaged from N0 to N2. While survival was not significantly affected between upstaged and non-upstaged patients, patients upstaged with multiple-station N2 had a significantly higher recurrence and lower survival compared to single-station N2.CONCLUSION:A combination of CK19, EpCAM and CEACAM5 gene expressions in lymph nodes can be used to identify micrometastasis which postoperatively may be used as a tool to predict patients' recurrence and survival.

Turkey stretches from the Balkans to the Middle East and is among the larger countries in terms of land area and population (Fig. 1). Turkey’s population of approximately 85 million people encompasses a diverse genomic, ethnic, and cultural heritage with roots from several empires and civilizations dating back to the Paleolithic age. According to the GLOBOCAN 20201 registry, lung cancer (LC) comprises 17.6% of all cancer types. It ranks highest in Turkey, with 41,000 new cases in 2020 and an age-adjusted incidence rate of 41.7 and 8.7 per 100,000 for men and women, respectively.

Recently, there has been a growing interest on the role of mitochondria in metastatic cascade. Several reports have shown the preferential utilization of glycolytic pathway instead of mitochondrial respiration for energy production and the pyruvate dehydrogenase (PDH) has been considered to be a contributor to this switch in some cancers. Since epithelial mesenchymal transition (EMT) is proposed to be one of the significant mediators of metastasis, the molecular connections between cancer cell metabolism and EMT may reveal underlying mechanisms and improve our understanding on metastasis. In order to explore a potential role for PDH inhibition on EMT and associated drug resistance, we took both pharmacological and genetic approaches, and selectively inhibited or knocked down PDHA1 by using Cpi613 and shPDHA1, respectively. We found that both approaches triggered morphological changes and characteristics of EMT (increase in mesenchymal markers). This change was accompanied by enhanced wound healing and an increase in migration. Interestingly, cells were more resistant to many of the clinically used chemotherapeutics following PDH inhibition or PDHA1 knockdown. Furthermore, the TGFβRI (known as a major inducer of the EMT) inhibitor (SB-431542) together with the PDHi, was effective in reversing EMT. In conclusion, interfering with PDH induced EMT, and more importantly resulted in chemoresistance. Therefore, our study demonstrates the need for careful consideration of PDH-targeting approaches in cancer treatment.

BACKGROUND:The term radiologic subsolid lung nodule (SLN) represents a heterogeneous group of non-neoplastic and neoplastic lesions. Intraoperative evaluation (IO) is often required to differentiate and diagnose. The current study aims to investigate the feasibility and reliability of scrape cytology (SC) and radiologic solid size correlation for the IO diagnosis of SLNs.METHODS:Sixty-eight patients with SLN signs were eligible to take part in the study due to intraoperatively prepared SC slides. We managed to complete the blind radiologic solid size measurement and cytologic evaluation retrospectively. Cases were grouped into three categories based on their cytological features: Group-0 (Benign), Group-1 (mild atypical features), and Group-2 (severe atypical features/unequivocally carcinoma). IO diagnoses were given by combining the radiologic solid size and cytological findings.RESULTS:Cytological features of Group-1 were observed in 100%, 93%, 32.5%, and 17% of the AIS, MIA, IA, and benign lesions, respectively. Cytological features of Group-2 were observed in 67.5%, and 7% of the IA and MIA, respectively. By combining cytology with radiologic solid size, 100%, 85%, 71%, and 83% of the AIS, IA, MIA, and benign lesions respectively were diagnosed correctly. Fifteen (15%) percent of the IA cases were underdiagnosed as MIA since their radiological solid sizes were less than 0.5 cm with cytological features of Group-1. Conversely, 29% of the MIA cases were overdiagnosed as IA since their radiological solid sizes were greater than 0.5 cm.CONCLUSION:SLNs should be handled with caution in terms of IO management. SC and radiologic solid size correlation both provide a practical and tissue-protecting approach for the IO evaluation of SLNs, ensuring a high consistency between IO and definitive diagnosis.

OBJECTIVES Whether acute phase and immune responses are minimally affected following minimally invasive lung surgery needs further investigation. We performed a pilot study to evaluate the immune profile of patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracic surgery lobectomies for the treatment of suspicious or known stage I non-small-cell lung cancer. METHODS Blood samples were taken preoperatively and 3 and 24 h postoperatively were analysed for C-reactive protein, glucose, cortisol, tumour necrosis factor alpha (TNF-α), interleukin 8 (IL-8) and interleukin 10 (IL-10) levels. TNF-α, IL-8 and IL-10 were also measured in lung tissues. T (CD4, CD8), B (CD19) and natural killer (CD56, CD16) cell counts and natural killer cell functions were analysed using a flow cytometry-based assay before and after surgery. RESULTS Minimally invasive surgery (robot-assisted thoracic surgery + video-assisted thoracoscopic surgery) significantly decreased IL-10 (P = 0.016) levels after surgery. No significant differences were detected in TNF-α (P = 0.48) and IL-8 (P = 0.15) levels before and after surgery. C-reactive protein (P < 0.001), cortisol (P < 0.001) and glucose levels (P < 0.001) increased significantly after surgery. Lymphocyte, total T cell, CD3+CD4+ and CD3+CD8+ CD16+CD56+ cell counts were significantly lower on postoperative day 1. CONCLUSION There seems to be a dynamic balance between pro- and anti-inflammatory cytokines and immune cells following minimally invasive lobectomy.

BACKGROUND:We aimed to assess the feasibility and short-term clinical outcomes of surgical procedures for cancer at an institution using a coronavirus disease 2019 (COVID-19)-free surgical pathway during the peak phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.MATERIALS AND METHODS:This was a single-center study, including cancer patients from all surgical departments, who underwent elective surgical procedures during the first peak phase between March 10 and June 30, 2020. The primary outcomes were the rate of postoperative SARS-CoV-2 infection and 30-day pulmonary or non-pulmonary related morbidity and mortality associated with SARS-CoV-2 disease.RESULTS:Four hundred and four cancer patients fulfilling inclusion criteria were analyzed. The rate of patients who underwent open and minimally invasive procedures was 61.9% and 38.1%, respectively. Only one (0.2%) patient died during the study period due to postoperative SARS-CoV2 infection because of acute respiratory distress syndrome. The overall non-SARS-CoV2 related 30-day morbidity and mortality rates were 19.3% and 1.7%, respectively; whereas the overall SARS-CoV2 related 30-day morbidity and mortality rates were 0.2% and 0.2%, respectively.CONCLUSIONS:Under strict institutional policies and measures to establish a COVID-19-free surgical pathway, elective and emergency cancer operations can be performed with acceptable perioperative and postoperative morbidity and mortality.

PURPOSE:The benefit of adjuvant chemotherapy for tumors smaller than 4 cm is not clear. We aimed to evaluate the prognostic impact of adjuvant platin-based chemotherapy in high-risk stage I patients with non-small cell lung cancer (NSCLC).METHODS:This cooperative group study included 232 NSCLC patients who underwent curative surgery for stage I disease with tumor size 2-4 cm. Re ults: Median age at presentation was 63 years (range 18-90). The mean tumor size was 29.6 ± 7.3 mm. The frequency of patients with specified risk factors were: visceral pleural effusion (VPI): n: 82 (36.6%); lymphovascular invasion (LVI): n: 86 (39.1%); Grade 3: n: 48 (32.7%); Solid micropapillary pattern (SMP): n: 70 (48.3%). Adjuvant platin-based chemotherapy was administered to 51 patients. During a median follow-up period of 50.5 months 68 patients (29.3%) developed recurrence, 54 (23.3%) died from any cause and 38 (16.4%) of them died of lung cancer. Patients who received chemotherapy compared with the non-chemotherapy group had a longer 5-years relapse-free survival (RFS) (84.5 vs 61.1%). Also on multivariate analysis, adjuvant chemotherapy was a significant independent prognostic factor for RFS.CONCLUSION:Adjuvant platin-based chemotherapy should be considered for patients with small tumors with adverse risk factors. Key words: adjuvant chemotherapy, lung cancer, oncology, lymphovascular invasion, solid-micropapillary pattern, platinum-based therapy.

Purpose In lung adenocarcinoma cases, 'spread through air spaces' (STAS) is a new indicator of invasion and directly related to disease survival. The aim of our study is to establish whether a preoperatively performed 18F-Fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging data can predict the presence of STAS in cases with lung adenocarcinoma and thus predict the decision for the type of surgery and adjuvant chemotherapy. Materials and methods Between 2000 and 2019, we retrospectively analyzed 63 patients with lung adenocarcinoma cases that had undergone lobectomy or pneumonectomy. Semiquantitative parameters were calculated and metabolic tumor volume (MTV)/CT volume (CTV) ratio was recorded from FDG PET/CT data. The pathological samples from these patients were evaluated for STAS. All these values were evaluated for their correlation with the alveolar spread. Results There was no statistically significant correlation to be found between CTV, MTV, total lesion glycolysis (TLG), standardized uptake value (SUV)(max), SUVmean and STAS (P > 0.05). However, MTV/CTV ratio above 1 had statistically more alveolar spread. In the group with an MTV ratio above 1, STAS positivity was 27 (75%), and 9 (25%) did not have STAS, whereas these were 6 (22.2%) patients who had STAS, and 21 (77.8%) did not have STAS in the group with below 1 (P < 0.001). Conclusions In the preoperative PET study inoperable lung adenocarcinoma cases, MTV/CTV ratio higher than 1 was found to predict STAS positivity. As a result, it was found that it provided significant clinical additional information regarding the need for a surgical approach (lobar resection instead of sublobar) and adjuvant chemotherapy.

Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common adult leukemia. The coexistence of CLL and papillary thyroid carcinoma (PTC) is extremely rare. PTC sometimes shows microscopic vascular invasion but rarely cause a tumor thrombus in the internal jugular vein (IJV). It is also rare to find both differentiated and poorly differentiated types of thyroid cancer in the same metastatic location. We report a case of 63-year-old Turkish man with history of CLL who had CLL/SLL involvement and PTC metastasis in the same lymph node. Additionally, there was macroscopic metastasis to the IJV with poorly differentiated areas in the removed tumor thrombus. Patient was treated with total thyroidectomy, left radical neck dissection, resection of the left IJV segment that contained the tumor thrombus and radioactive iodine (RAI) therapy. Furthermore, metastatic lesions were found in the brain, lung and bone. Radiotherapy and chemotherapy were performed. However, our patient died approximately 12 months after thyroidectomy. To our knowledge, our present report is the first description with its current features.

Background/aim:Programmed death ligand-1 (PD-L1) is a predictive marker for immunotherapeutic agents. However, heterogeneous staining of PD-L1 can cause false-negative results. The aim of this study is to evaluate the importance of histological patterns on PD-L1 staining heterogeneity in lung adenocarcinomas (LAC).Materials and methods:PD-L1 immunohistochemistry (IHC) stain was performed to two different tissue cores of 128 LAC cases, and cut-off values are given for grouping the cases according to the percentage of staining (1%-10%, 11%-49%, 50%-100%). Staining rates between cores were compared and analyzed by their histological patterns. Also, the relation of the PD-L1 expression with the clinicopathological characteristics of the cases was analyzed.Results:Overall, PD-L1 expression was observed in 53 of 128 cases (41.4%, 1% cut-off), 23.5% of them were positive at 10% cut-off and 14.1% at 50% cut-off. PD-L1 expression was significantly related to the high grade micropapillary and solid patterns of adenocarcinomas (p:0.01). Staining cut-offs were mostly similar between cores (43/50, 86%) (k:0.843). However, 14% of them were positive only in one core (7 of 50). This false negativity was mostly related to the histological patterns.Conclusion:Our data reveal the heterogeneous staining of PD-L1 expression, also micropapillary and solid patterns show higher rates of PDL expression. Therewithal, these findings also highlight the importance of taking into consideration of histological patterns, when choosing a paraffin block for the PDL1.