Tracing tumor heterogeneity of pleomorphic carcinoma of the lung.

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is an aggressive and highly heterogeneous non-small-cell lung carcinoma whose underlying biology is still poorly understood. METHODS: Forty-two tumor areas from 20 PPC patients were microdissected, including 39 primary tumors and 3 metastases and the histologically distinct components were subjected to whole exome sequencing (WES) separately. We further performed in silico analysis of microdissected bulk RNAseq and methylation data of 28 samples from 14 PPC patients. We validated our findings using immunohistochemistry. RESULTS: The epithelial and the sarcomatoid components of PPCs shared a large number of genomic alterations. Most mutations in cancer driver genes were clonal and truncal between the two components of PPCs suggesting a common ancestor. The high number of alterations in the RTK-RAS pathway suggests that it plays an important role in the evolution of PPC. The metastases morphologically and genetically resembled the epithelial or the sarcomatoid components of the tumor. The transcriptomic and epigenetic profiles of the sarcomatoid components of PPCs with matched squamous-like or adenocarcinoma-like components differed from each other and they shared more similarities to their matched epithelial components. NCAM1/CD56 was preferentially expressed in the sarcomatoid component of squamous-like PPCs, whereas CDH1/E-Cadherin expression was downregulated in the sarcomatoid component of most PPCs. CONCLUSION: LUAD-like PPCs are mainly driven by RTK-RAS signaling, whereas epithelial-mesenchymal transition programs as highlighted by increased NCAM1 and decreased CDH1 expression govern the epithelial-sarcomatoid transition between the clonally related tumor components. Several alterations in PPCs pinpoint therapeutic opportunities.

Retrospective Analyses of PD-L1, LAG-3, TIM-3, OX40L Expressions and MSI Status in Gastroenteropancreatic Neuroendocrine Neoplasms.

We investigated expressions of PD-L1, LAG-3, TIM-3, and OX40L as immune checkpoint proteins, and MSI (repetitive short-DNA-sequences due to defective DNA-repair system) status were analyzed with immunohistochemistry from tissue blocks. Of 83 patients, PD-L1 expression was observed in 18.1% (n = 15) of the patients. None of the patients exhibited LAG-3 expression. TIM-3 expression was 4.9% (n = 4), OX40L was 22.9% (n = 19), and 8.4% (n = 7) of the patients had MSI tumor. A low-to-intermediate positive correlation was observed between PD-L1 and TIM-3 expressions (rho: 0.333, p < 0.01). Although PD-L1 expression was higher in grade 3 NET/NEC, MSI status was prominent in grade 1/2 NET.

Is flow cytometry useful in determining central nervous system involvement in patients with hematological malignancy? Analysis with a prospective cohort.

Central nervous system (CNS) involvement occurs in approximately 5-15% of patients in hematological malignancies. Early diagnosis and treatment is essential for a successful approach to CNS involvement. The gold standard method for diagnosis is cytological evaluation, but its sensitivity is low. Flow cytometry (FCM) from cerebrospinal fluid(CSF) is another method used to identify small groups of cells with abnormal phenotype. In our study, we compared FCM and cytological findings in the evaluation of CNS involvement in our patients with hematological malignancies. 90 patients [58 males, 32 females] were included in the study. CNS involvement was positive in 35(%38.9) patients, negative in 48(%53.3) patients, and suspicious (atypical) in 7(%7.8) patients by flow cytometry and it was positive in 24(%26.7) patients, negative in 63(%70) patients, and atypical in 3(%3.3) patients by cytology. While the sensitivity and specificity were found to be respectively 68.5% and 100% by cytology, it was found to be 94.2% and 85.4% by flow cytometry. Flow cytometry, cytology and MR findings were significantly correlated with each other in both prophylaxis (p < 0.001) and patients with prediagnosis of CNS involvement. Although the gold standard diagnostic method in the diagnosis of CNS involvement is cytological, its sensitivity is low and it can give false negative results at a rate of 20-60%. Flow cytometry is an ideal objective and quantitative method for identifying small groups of cells with abnormal phenotype. Flow cytometry can be used routinely in the diagnosis of CNS involvement in patients with hematological malignancies with cytology, since it can detect fewer malignant cells, has a higher sensitivity, and provides easy and faster results.

Comparison of PD-L1 and VISTA expression status in primary and recurrent/refractory tissue after (chemo)radiotherapy in head and neck cancer.

BACKGROUND: PD-L1 and VISTA are thought to play a role in escape from the immune system, tumor progression, and treatment response in tumoral tissue. The current study aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on PD-L1 and VISTA expression in head and neck cancers. METHODS: PD-L1 and VISTA expression were compared between the primary biopsy taken at the time of diagnosis and refractory tissue biopsies of patients who received definitive CRT or recurrent tissue biopsies of patients who had surgery followed by adjuvant RT or CRT. RESULTS: In total, 47 patients were included. Radiotherapy had no effect on the expression levels of PD-L1 and VISTA in patients with head and neck cancer (p = 0.542 and p = 0.425, respectively). A positive correlation was found between PD-L1 and VISTA expression (p < 0.001; r = 0.560). PD-L1 and VISTA expression in the first biopsy were found to be significantly higher in clinical lymph node-positive patients compared to node-negative patients (PD-L1 p = 0.038; VISTA p = 0.018). The median overall survival of patients with ≥ 1% VISTA expression in the initial biopsy was significantly shorter than that of patients with < 1% VISTA expression (52.4 vs. 110.1 months, respectively; p = 0.048). CONCLUSION: It was found that PD-L1 and VISTA expression did not change with RT or CRT. Further studies are needed to evaluate the relationship of PD-L1 and VISTA expression with RT and CRT.

LAG-3 expression in tumor microenvironment of triple-negative breast cancer.

BACKGROUND: This study aimed to evaluate the expression of lymphocyte activation gene-3 (LAG-3) and its relationship with programmed cell death ligand-1 (PD-L1) in triple-negative breast cancer (TNBC). METHODS: : LAG-3 and PD-L1 was evaluated in tumor-infiltrating lymphocytes (TILs) using immunohistochemistry (IHC). The chi-square test was used to estimate the associations between LAG-3, PD-L1 and clinicopathological characteristics. Correlation between LAG-3 stromal TIL (sTIL), LAG-3 intraepitelial TIL (iTIL) and PD-L1 was assessed with using the Spearman's correlation coefficient. Survival analysis was performed using the Kaplan-Meier method. RESULTS: The percentages of LAG-3 sTIL+, LAG-3 iTIL+, PD-L1+ tumor cells and PD-L1+ inflammatory cells were 52%, 42%, 14% and 70%, respectively. A strong positive correlation between LAG-3 sTIL and LAG-3 iTIL (r = 0.874, p < 0.001) and a moderate positive correlation between LAG-3 sTIL and PD-L1 (r = 0.584, p < 0.001) were found. LAG-3 and PD-L1 status did not significantly affect overall survival (OS) (HR: 0.56 (95% CI: 0.15-2.11) (p = 0.397), HR: 2.70 (95% CI: 0.56-13.02) (p = 0.215), respectively). DISCUSSION: High levels of LAG-3 and PD-L1 expression were detected in patients with TNBC. Although their contribution to survival could not be determined, the high expression rates of PD-L1 and LAG-3 may help identify the subgroup of TNBC that would benefit from immunotherapy.

Could PD-L1 positivity be associated with venous thrombosis in patients with non-small cell lung cancer?

The risk of venous thromboembolism (VTE) is increased in non-small cell lung cancer (NSCLC), and defining at-risk patients is important. Thus, we aimed to assess the association between programmed cell death ligand 1 (PD-L1) expression and VTE [pulmonary embolism (PE), deep venous thrombosis (DVT)] in NSCLC. In this retrospective, observational multicentre study, 369 patients with NSCLC who had PD-L1 immunohistochemistry based on biopsies taken between January 2017 and December 2019, were divided as PD-L1-positive (n = 181) and -negative (n = 188) groups, and low-positive (n = 99) and high-positive (n = 82) PD-L1 groups. Among all population, 12.5% of them developed a VTE during a median follow-up of 474 days. The rates of DVT, PE, and PE + DVT were 5.7%, 6% and 0.8%, respectively. VTE (15.5% vs. 9.5%) and DVT (3.8% vs. 7.4%) were similar between two groups, while PE was significantly higher in PD­L1-positive group than those in PD-L1-negative group (11.1% vs 1%, p < 0.001). There were no significant differences between low- and high-positive groups in terms of VTE (14.1% vs. 17%), PE (12.1% vs. 9.8%), and DVT (2% vs. 6.1%). In the multivariate analysis, multiple metastases (Hazard ratio [HR] 4.02; 95% confidence interval [Cl] 1.18-13.63; p = 0.07) and PD-L1 positivity was associated with an increased PE risk (HR 8.39; 95% Cl 2.07-34.07; p = 0.003). In conclusion, PD-L1 positivity may be of important role in predicting the increased risk of PE in patients with NSCLC and thereby may be used to define patients likely to benefit from thromboprophylaxis.

Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma.

Evoked from asbestos-induced inflammation, pleural mesothelioma represents a fatal diagnosis. Therapy ranges from nihilism to aggressive multimodality regimens. However, it is still unclear who ultimately benefits from which treatment. We aimed to re-challenge inflammatory-related biomarkers' prognostic value in times of modern immune-oncology and lung-sparing surgery. The biomarkers (leukocytes, hemoglobin, platelets, neutrophils, lymphocytes, monocytes, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), C-reactive protein (CRP)) and clinical characteristics (age, sex, histology, therapy) of 98 PM patients were correlated to overall survival (OS). The median OS was 19.4 months. Significant OS advantages (Log-Rank) were observed in multimodal treatment vs. others (26.1 vs. 7.2 months, p < 0.001), surgery (pleurectomy/decortication) vs. no surgery (25.5 vs. 3.8 months, p < 0.001), a high hemoglobin level (cut-off 12 g/dL, 15 vs. 24.2 months, p = 0.021), a low platelet count (cut-off 280 G/L, 26.1 vs. 11.7 months, p < 0.001), and a low PLR (cut-off 194.5, 25.5 vs. 12.3 months, p = 0.023). Histology (epithelioid vs. non-epithelioid, p = 0.002), surgery (p = 0.004), CRP (cut-off 1 mg/dL, p = 0.039), and platelets (p = 0.025) were identified as independent prognostic variables for this cohort in multivariate analysis (Cox regression, covariates: age, sex, histology, stage, CRP, platelets). Our data verified the previously shown prognostic role of systemic inflammatory parameters in patients treated with lung-sparing surgery within multimodality therapy.

Effect of neoadjuvant therapy on tumor tissue PD-L1 and VISTA expression levels in non-small-cell lung cancer.

Background: PD-L1 and VISTA are important checkpoint control stations and play an immunomodulatory role in patients with non-small-cell lung cancer. Method: The expression levels of PD-L1 and VISTA between pre- and post-treatment tumor tissue were compared. Results: While PD-L1 expression was >1% in 35% of patients before neoadjuvant therapy, PD-L1 expression was >1% in 65% of patients after treatment (p = 0.004). VISTA expression was >1% in 41% of patients before treatment, and this rate was 65% after treatment (p = 0.025). Conclusion: Chemotherapy and chemoradiotherapy can be used as immunizers by increasing PD-L1 and VISTA expression levels.

Primary Subretinal Hydatid Cyst Presenting as Leukocoria in a Child.

PURPOSE: To describe a case of subretinal hydatid cyst presenting as leukocoria and treated with limbal vitrectomy. METHODS: A single case report demonstrated by multimodal imaging. RESULTS: An otherwise healthy 28-month-old boy was admitted to our hospital with a complaint of leukocoria and underwent combined lensectomy and vitrectomy under albendazole therapy due to vitreous space-occupying subretinal cyst. Systemic workup showed no involvement in other organs. Cyst content was adequately aspirated with a 39-gauge needle, the cyst wall was freed from surrounding attachments to the retina and the nasal choroid and was extracted through a limbal incision using a cryoprobe. Nasal retinotomy and retinectomy area was lasered and tamponaded with silicone oil. Histopathologic examination confirmed the diagnosis of hydatid cyst disease. Silicone oil was removed at postoperative 3rd month. Retina stayed attached and the patient had a fix and follow vision under contact lens and amblyopia treatment during the 21 months follow-up period. CONCLUSION: This is the youngest subretinal hydatid cyst case in the literature. Large subretinal hydatid cyst may rarely cause leukocoria in children without any involvement in other organs. Vitrectomy with limbal approach and 39G needle-assisted cyst fluid aspiration and cryo-extraction appears to be a safe and successful surgical option in such cases.

Eltrombopag may induce bone marrow fibrosis in allogeneic hematopoietic stem cell transplant recipients with prolonged thrombocytopenia.

Poor graft function (PGF) and secondary failure of platelet recovery (SFPR) are significant causes of transplant related morbidity and mortality. Although thrombopoietin receptor agonists (TPO-RA), particularly Eltrombopag (EPAG), have been reported to be efficacious in the treatment of prolonged thrombocytopenia, potential long term adverse effects remain to be elucidated. This retrospective study was performed to determine the efficacy and toxicity profile of TPO-RAs in allogeneic hematopoietic stem cell transplant (alloHCT) recipients. Medical records of 27 patients [median age: 55(21-73) years; male/female: 15/12] who received posttransplant EPAG for SFPR or PGF were analysed. Eltrombopag was started on day 110(33-670) after transplant. Median initial dose was 25(25-50) mg/day which was properly escalated to a maximum dose of 75(50-100) mg/day. Duration of the treatment was median 120(31-377) days. Overall response rate (ORR) was 59.3% in the study population. Time-to-treatment response was 42(3-170) days. Mild-to-moderate bone marrow fibrosis was detected in the posttreatment biopsies of 12/22 patients (54.5%), 9 of whom did not represent any grade of myelofibrosis in their inital biopsies. The grade of posttreatment fibrosis was significantly increased when time-to-treatment response was longer (p = 0.008). Long term use of TPO-RAs may be considered as a potential cause of myelofibrosis in alloHCT recipients.

Histologic and Immunohistochemical Evaluation of Radiosurgery in Strabismus Surgery in a Rabbit Model.

PURPOSE: The aim of this study was to evaluate the use of monopolar radiosurgery (MRS) assisted strabismus surgery and to compare its histologic and immunohistochemical wound healing outcomes with conventional surgery. METHODS: Superior rectus muscle resection was performed on 30 white rabbits with three different surgical muscle cutting techniques: monopolar radiosurgery (MRS group), conventional scissors preceded by bipolar electrocautery (BEC group), and conventional scissors with no cauterization (control group). Degree of tissue injury, bleeding, inflammation, and fibrosis, as well as wound healing rate (CD68+ cell number), were evaluated. RESULTS: In CS group, hemorrhage scores were significantly higher than those in the other groups (MRS group: Z = 5.182; p < 0.001 and BEC group: Z = 4.463; p < 0.001) and MRS group had lower scores than BEC group; however, the difference was not significant (Z = 1.423; p = 0.211). The tissue injury score in BEC group was higher when compared with MRS, and the difference was statistically significant (p = 0.028). Median inflammation scores at days 1 and 21 were lowest in MRS group, but the difference was not statistically significant among groups (day 1; p = 0.115, day 21; p = 0.095). The median fibrosis score was higher in the control group, when compared with MRS, and the difference was statistically significant (muscle-sclera; p = 0.011 and muscle-conjunctiva: p = 0.003). The macrophage score (number of CD68+ cells) was lowest in CS group; however, the difference was not significant (p = 0.657). CONCLUSIONS: Monopolar radiosurgery is a novel method for strabismus surgery and provides equivalent hemostasis effects and wound healing properties, compared with conventional methods, and enhances surgeon comfort, as muscle incisions are made in one step with clean surgical area.

Pediatric EBV Positive Mucocutaneous Ulceration in Stomach a Rare Entity.

Epstein Barr virus (EBV) related lymphoproliferative diseases may occur in immunocompromised patients or patients with a history of drug use causing immunodeficiency. EBV positive mucocutaneous ulceration in the new classification of lymphoproliferative diseases in 2016 is very rare in children. Involvement occurs in the skin, oral mucosa, and gastrointestinal system. Gastric involvement is very rare in the literature. There is no case of gastric involvement in children. There are no specified modalities in the treatment of EBV positive mucocutaneous ulceration. We presented our pediatric patient with ataxia telangiectasia who presented with abdominal pain and difficulty swallowing and diagnosed with EBV positive mucocutaneous ulceration in the stomach. We started brentuximab vedotin during the treatment process, and complete remission was achieved after 6 cures of treatment. Our patient is the first case of EBV positive mucocutaneous ulceration in the pediatric case series.

"How long does crizotinib work? a rare case of recurrent inflammatory myofibroblastic tumor".

Inflammatory myofibroblastic tumors (IMTs) are mesenchymal solid tumors, in which anaplastic lymphoma kinase (ALK) gene rearrangement might be detected. A 48-year-old female presented with IMT of lung, treated with surgery. After a 39-month disease-free survival metastatic recurrence was occurred involving soft tissues both infra- and supradiaphragmatic regions. The biopsies obtained from metastatic regions confirmed the recurrence with ALK rearrangement in immunohistochemistry. Initial partial response observed early in treatment course remained as a stable disease with crizotinib treatment. Although an excellent outcome with overall survival of 57 months was observed in our case, there is not enough information about survivals with crizotinib and the treatment options beyond progression. Therefore, every individual case has a unique value paving the way for more effective treatment.

Dose-related effects of dexmedetomidine on sepsis-initiated lung injury in rats.

BACKGROUND: Sepsis is one of the leading causes of death in intensive care units. Dexmedetomidine is a sedative agent with anti-inflammatory properties. This study is designed to differentiate the impact of two different doses of dexmedetomidine on lung injury induced by sepsis. METHODS: Adult male Wistar rats were randomly divided into four groups: sham (n = 6), control (n = 12), 5DEX (n = 12), and 10DEX (n = 12). Cecal ligation puncture (CLP) was applied for sepsis initiation. The 5DEX group received 5 µg.kg-1.h-1 and the 10DEX group received 10 µg.kg-1.h-1 dexmedetomidine intravenous infusions for a 1-hour period. Six hours after CLP, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and intercellular adhesion molecule-1 (ICAM-1) levels were analyzed in blood samples. Twenty-four hours after CLP, lung samples from the remaining rats were collected for the measurement of myeloperoxidase (MPO) activity, histological examination, and TdT- (terminal deoxynucleotidyl transferase) mediated fluorescent-dUTP labeling staining for apoptosis detection. RESULTS: Serum cytokine release, MPO activity, and apoptosis in the lung were significantly increased in the CLP group compared with the sham and dexmedetomidine groups (p < 0.05). TNF-α, ICAM-1, and MPO were significantly lower in the 10DEX group compared with both 5DEX and control groups, while IL-1ß, total injury score, and apoptotic cell count had significantly lower values in both 10DEX and 5DEX groups compared with the control group (p < 0.05). CONCLUSION: Dexmedetomidine administration played a protective role against CLP-induced lung injury. High-dose dexmedetomidine was needed for suppressing the leukocyte-mediated lung injury and apoptosis of lung tissue.

The effect of EML4-ALK break-apart ratio on crizotinib outcomes in non-small cell lung cancer harboring EML4-ALK rearrangement.

PURPOSE: Anaplastic lymphoma kinase (ALK) gene rearrangement exists in approximately 3-7% of non-small cell lung cancer (NSCLC) and more than 15% split or isolated red signals among 50 tumor nuclei scored in the FISH analysis defines as ALK-positive. The previous studies showed that the high EGFR mutational load related to better outcomes in EGFR mutant NSCLC. Therefore, we aimed to investigate the effect of the ALK break-apart ratio on treatment outcome in metastatic ALK-positive NSCLC. METHODS: The patients (pts) who ALK-positive and treated with crizotinib were retrospectively enrolled. The 30%, 40%, 50%, 60%, and 70% break-apart ratios were determined as a threshold value, and each of these was evaluated separately. Based on the results of these analyses, we detected the optimal threshold value and also performed further investigations. RESULTS: A total of 70 patients were enrolled in the study. The most significant decrease in the risk of the progression or death was detected at the 50% threshold value and it was accepted as the optimal threshold. The median PFS was 17.9 vs. 7.06 months (mo) in the pts with high ALK rearrangement than low (HR: 0.43, 95% CI 0.24-0.76, p 0.004). The median OS was also significant longer in high ALK rearrange group (44.6 mo vs. 16.8 mo; HR: 0.37, 95% Cl 0.1883-0.7315; p 0.004). The intracranial progression during crizotinib treatment was significantly frequent in the pts with high ALK rearrangement (62.5-32.5%, P 0.039) DISCUSSION: In this study, we found that the high break-apart ratio can predict the extent of benefit from targeted therapy in ALK-positive NSCLC patients. Based on the results of this study, the percentage of the ALK rearrangement can be used to predict treatment outcome and to choose the optimal targeted agent in the treatment of metastatic ALK-positive NSCLC.

PD-L1 expression in immune cells is a favorable prognostic factor for nasopharyngeal carcinoma.

BACKGROUND: Programmed death-ligand 1 (PD-L1) has been determined as a reliable prognostic factor for various malignancies. In this study, we aimed to determine the prognostic effect of PD-L1 expression in tumor-infiltrating immune cells (TIICs) of nasopharyngeal carcinoma (NPC) patients. METHODS: Seventy patients diagnosed with non-metastatic NPC were included in the study. PD-L1 expression on immune cells was analyzed by immunohistochemical method. Patients were categorized into two groups according to the PD-L1 expression level in TIICs (level of PD-L1 staining ≥5% positive vs <5% negative). RESULTS: Median follow-up period was 34 months (range = 1 - 188). 1 and 2 years survival rate were found as 75% and 63% in PD-L1 negative TIICs group (47%), and 85% and 83% in PD-L1 positive TIICs group (53%), respectively. PD-L1 positivity in immune cells (ICs) was detected in 53% of the patients. The survival rate was found better in the PD- L1 positive group compared to the negative group (P = 0.049). DISCUSSION: In conclusion, the survival rate was found significantly better in the PD-L1 positive TIICs group, compared to the negative group.

Clinicopathological and Prognostic Significance of the EML4-ALK Translocation and IGFR1, TTF1, Napsin A Expression in Patients with Lung Adenocarcinoma.

OBJECTIVE: Patients with lung adenocarcinoma who harbor ALK gene rearrangements can demonstrate significant clinical benefit with ALK tyrosine kinase inhibitors. Insulin-like growth factor receptor 1 (IGFR1) is a cellular membrane receptor that is overexpressed in many tumors. It plays an important role in cancer progression and is associated with increased postoperative recurrence and poorer disease-free survival. The aim of this study was to determine the EML4-ALK mutation and IGFR1 expression in lung adenocarcinoma and analyze their prognostic value. MATERIAL AND METHOD: In this study, we analyzed the EML4-ALK mutation using the FISH and IHC techniques in 251 lung adenocarcinoma (203 primary resections, 48 metastasectomies) cases. Correlative analyses were performed between the EML4-ALK mutation, the IGFR1, TTF1, and NapsinA expression, and the clinicopathologic factors in lung adenocarcinomas. RESULTS: The EML4-ALK mutation was observed in 3.8% of the cases and it was associated with the solid pattern, signet ring cell morphology, and larger tumor size. IGFR1 expression was identified in 49% of the cases and most of the ALK-mutated cases were also expressing the IGFR1 protein (66%). IGFR1 expression frequency was increased in metastasectomy specimens. CONCLUSION: A solid signet-ring cell pattern or mucinous cribriform pattern was present at least focally in all ALK-positive tumors, consistently with the literature. In addition, IGFR1 expression levels showed an increase in the EML4-ALK-mutated cases in our series, but the clinical significance of this finding should be supported by larger series and survival analysis. Our findings show that IGFR1 expression may be useful as a poor prognostic marker in patients with lung adenocarcinoma.

Programmed death ligand-1 expression levels, clinicopathologic features, and survival in surgically resected sarcomatoid lung carcinoma.

AIM: To determine the programmed death ligand-1 (PD-L1) expression rates in sarcomatoid lung carcinomas and to compare clinicopathologic features and survival rates of PD-L1-positive and negative patients. METHODS: PD-L1 expression was evaluated in 65 surgically resected sarcomatoid carcinomas. The clinicopathologic features of cases with PD-L1-positive and negative tumors were compared. Kaplan-Meier survival analysis was performed. Multiple Cox proportional hazard regression analysis was performed to determine independent predictors of overall survival. RESULTS: PD-L1 antibody positivity was found in 72.3% of surgically resected sarcomatoid lung carcinomas. Regarding histopathologic subtypes, PD-L1 expression was positive in 80.4% of pleomorphic carcinomas, 62.5% of spindle- and/or giant-cell carcinomas, and 16.7% of carcinosarcomas. Pleural invasion was observed in 68.1% of PD-L1-positive cases and 27.8% of PD-L1-negative cases (P = 0.008). No difference in survival was found between PD-L1-positive and -negative tumors. The only factor significantly associated with poor survival was the pathological stage of the tumor. CONCLUSIONS: This study reveals a high rate of PD-L1 positivity in a large number of sarcomatoid lung carcinoma cases with pleomorphic carcinoma, spindle- and/or giant-cell carcinoma, and carcinosarcoma subtypes. The only significantly different clinicopathologic feature in PD-L1-positive cases is pleural invasion. PD-L1 positivity is not a significant predictor of survival in sarcomatoid lung carcinomas.

Good prognostic factor in patients with nonmetastatic nasopharyngeal carcinoma: Programmed death ligand-1 expression in tumor cells.

PURPOSE: Programmed death ligand-1 (PD-L1) is the main ligand for programmed death-1 (PD-1), and is one of the major targets for cancer immunotherapy. Only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). There is a controversial association between PD-L1 expression and survival in NPC. This study aimed at defining any potential association between PD-L1 expression in tumor cells (TCs) and prognosis in NPC. PATIENTS AND METHODS: A total of seventy NPC patients treated between January 2008 and December 2016 were included in the study. PD-L1 expression was assessed by immunohistochemistry (IHC) in tumor specimens. The IHC assay was considered positive if ≥5% of TCs are stained. Clinicopathological variables were documented. Variables included in the analysis were PD-L1 expression, clinicopathological characteristics, and prognosis. RESULTS: The estimated 5-year overall survival (OS) rate was 62%. Nearly 55.7% (n = 39) of the TCs tested positive for PD-L1 expression. No associations were found between the level of PD-L1 in TCs and clinicopathological characteristics. Comparisons between patients with PD-L1-positive tumors and PD-L1-negative tumors revealed that OS was statistically significantly longer in patients with PD-L1-positive tumors as assessed by the univariate Cox regression analysis (hazard ratio [HR], 0.378; 95% confidence interval, 0.158-0.905; P = 0.029) and Kaplan-Meier curves (P = 0.023). CONCLUSION: PD-L1 expression is an important prognostic factor in NPC. PD-L1 expression positively correlates with survival.

The association of clinicopathologic features and peripheral blood parameters with high PD-L1 expression in non-small cell lung cancer.

INTRODUCTION: Programmed death ligand 1 (PD-L1) is a marker that widely used for prediction of response to immunotherapy. Dynamic alteration of PD-L1 expression are the major problems for reflection of the actual status of the PD-L1. So, we aimed to investigate the factors that may be associated with PD-L1 expression in lung cancer. MATERIALS AND METHODS: The patients diagnosed with non-small cell lung cancer were enrolled, retrospectively. The patients were stratified according to PD-L1 expression level as ≥ 50% and < 50%. RESULT: Totally, 217 patients were enrolled. The clinicopathologic features were similar between two groups, except the amount of cigarette consumption. Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and systemic immune-inflammmotry index were found significantly lower in PD-L1 ≥ 50% (p< 0.001, p= 0.006 and p= 0.003, respectively) and also negatively correlated with PD-L1 level (rho= -0.255, p< 0.001; rho= -0.17, p= 0.013; rho= - 0.185, p= 0.006, respectively). CONCLUSIONS: According to the results of our study, peripheral blood parameters can be used to the prediction of the high PD-L1 expression and can be used for reflection of current PD-L1 expression.