Expression Rate Of Programmed Death Ligand 1 Research Articles

PD-L1 Expression on Tumor Cells Is Associated With a Poor Outcome in a Cohort of Caucasian Nasopharyngeal Carcinoma Patients.

Background: Nasopharyngeal carcinoma (NPC) is endemic in East Asia but rare in the western world. Programmed death ligand 1 (PD-L1) expression on NPC correlates with clinical outcomes. However, data for Caucasian NPC patients are missing. Thus, we performed this retrospective analysis for investigating the potential association of immune checkpoint protein expression with outcome parameters in Caucasian NPC patients.Methods: Fifty-five patients with NPC treated between 1993 and 2018 at the Medical University of Vienna were identified. After the exclusion of Asian patients, data on baseline demographic, tumor stage, overall survival (OS), and disease-free survival (DFS) of 30 patients were analyzed. Their tumor samples were stained and scored (low vs. high) for PD-L1, programmed death receptor 1 (PD-1), lymphocyte activating gene 3 (LAG3), and cluster of differentiation 8 (CD8) antibodies. Statistical analysis was performed with Kaplan-Meier plots and log-rank test. Estimated hazard ratios of dichotomized analysis were calculated, together with 95% confidence intervals and p-values of Wald tests.Results: PD-L1 expression was ≥50% in 6 (20%) patients, whereas 19 (63%) had ≥1% expression and 5 (17%) tumor samples were PD-L1-negative. While sex and age had no impact on DFS or OS, <50% PD-L1 expression on tumor cells (TC) was associated with a significantly longer OS (log rank test p = 0.037; HR 0.275; 95% CI 0.073–1.03). There was no influence on DFS (log rank test p = 0.34; HR 0.599; 95% CI 0.208–1.728). However, <10% PD-L1 expression on tumor infiltrating lymphocytes (TILs) was correlated with a worse DFS (log rank test p = 0.0057; HR 4.06; 95% CI 1.389–11.868). LAG3 expression or the number of TILs did not play any prognostic role in our population.Conclusion: The PD-L1 expression rate on Caucasians was comparable to that in Asian patients. Although these results have to be interpreted with caution due to the limited number of Caucasian patients available, our data suggest that ≥50% PD-L1 expression on TC is associated with a poor outcome, while ≥10% PD-L1 expression on TILs is correlated with improved DFS. A prospective biomarker analysis of a predefined Caucasian NPC subpopulation would be desirable in future trials.

PD-L1 EXPRESSION IN SUBTYPES OF ADENOCARCINOMA OF THE LUNG

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Programmed death-ligand 1 (PD-L1) inhibitors are group of new drugs proved efficacy in many kinds of cancer including non-small cell lung cancer(NSCLC). However, the response rate is only 20∼30%. Although immunohistochemical staining for PD-L1 is useful predictive biomarker of PD-1 and PD-L1 inhibitors, there are some limitations. One of the presumptive cause of discordance of PD-L1 expression and response to PD-1 and PD-L1 inhibitors is heterogeneity of tumor tissue. Clinical suspicion is one of most important factor of further evaluation, including rebiopsy. We examined whether PD-L1 expression is different in subtypes of adenocarcinoma of the lung to predict expression of PD-L1. METHODS: I examined tumor tissues of 195 patients who were operated during January 2007 and December 2018. PD-L1 staining was performed utilizing the DAKO FDA-approved PD-L1, 22C3 pharmDx™ protocol using the Dako Automated Link 48 platform. Pathologist examined tumor tissues after cutting tissue slides for viable tumor tissue. The specimen should be considered PD-L1 positive if tumor proportion score greater than 50% of the viable tumor cells exhibit membrane staining at any intensity. Adenocarcinoma was classified according to predominant growth pattern. RESULTS: Tumor samples showed PD-L1 staining positive were 20 out of 195(10.3%). In descending order of subtype of adenocarcinoma were signet ring cell type (50.0%), acinar type (15.0%), solid type (9.7%), nonmucinous lepidic type (7.8%), micropapillary type (0%). The rate of PD-L1 expression in older archival tissues is not lower compared with newer fresh samples. CONCLUSIONS: Overall expression rate of PD-L1 was lower than previously reported. Different subtypes of adenocarcinoma showed different ratio of PD-L1 positivity. CLINICAL IMPLICATIONS: There is tendency of higher rate of PD-L1 positive in histologic subtypes known as poor prognostic type. DISCLOSURES: No relevant relationships by Choonhee Son, source=Web Response

Expression of programmed death ligand 1 in liver cancer and its clinical significance

Objective To investigate the expression of programmed death ligand 1 (PD-L1) in liver cancer tissues and its clinical significance. Methods The expression levels of PD-L1 in 110 liver cancer tissues, including 95 cases of hepatocellular carcinoma and 15 cases of cholangiocarcinoma were detected by using immunohistochemical staining method, and the relationship between PD-L1 expression and the clinicopathological characteristics of patients with hepatocellular carcinoma was analyzed. Results Immunohistochemistry results showed that the positive rate of PD-L1 in liver cancer tissues was 69.1% (76/110), and the positive rate of membrane and cytoplasm was 46.4% (51/110) and 22.7% (25/110), respectively. The positive rate of PD-L1 expression in hepatocellular carcinoma was higher than that in cholangiocarcinoma [78.9% (75/95) vs. 6.7% (1/15)], and the difference was statistically significant (χ 2 = 31.693, P 0.05). Further analysis showed that protein expression localization of PD-L1 was closely related to the pathological grade in hepatocellular carcinoma (P = 0.013). Conclusion The positive expression of PD-L1 in hepatocellular carcinoma is closely associated with depth of invasion and TNM stage, which provides a theoretical basis for the immunotherapy of liver cancer targeting PD-L1. Key words: Liver neoplasms; Programmed death ligand 1; Immunohistochemistry

Association Between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma.

Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score ≥1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4%) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4% and 57.9% (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95% confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40%) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.

Frequency of discordance in programmed death ligand 1 (PD-L1) expression between primary tumors and paired distant metastases in advanced cancers: A systematic review and meta-analysis.

e14290 Background: Randomized trials have demonstrated that PD-L1 expression in tumor cells predicts for response to PD-1 or PD-L1 checkpoint inhibitors in advanced cancers. However, the frequency of discordance in PD-L1 expression between primary tumors and paired distant metastases is currently unclear. We aimed to determine the discordance rate of PD-L1 expression between primary tumor and paired distant metastases in advanced cancers. Methods: We searched MEDLINE and EMBASE for eligible studies. We noted the discordance rate (positive-to-negative or vice versa) and performed subgroup analyses based on the PD-L1 expression in primary tumor, locations of primary tumor and distant metastases, positivity thresholds and type of antibody used for testing. We used QUADAS-2 tool to assess the methodologic quality of the included studies. We performed the meta-analysis using the logistic-normal random effects model. Results: We identified 11 eligible studies including 351 cases of lung, colorectal, breast and ovarian cancers. Nine studies were judged to have low risk of bias in their methodological quality. The overall discordance rate in PD-L1 expression between primary tumor and paired distant metastases was 28% (95% confidence interval (CI) = 18-41) with significant heterogeneity among the studies (chi-square test P-value &lt; 0.0001). There was no statistically significant differences in discordance rates between the subgroups: PD-L1-positive (40%, 95% CI = 21-63) vs PD-L1-negative primary tumors (21%, 95% CI = 12-34), lung primary (31%, 95% CI = 14-55) vs colorectal/ breast/ ovarian primary (27%, 95% CI = 19-37), central nervous system metastases (22%, 95% CI = 8-47) vs liver/ lung/ pleural/ peritoneum metastases (34%, 95% CI = 24-46); 1% (23%, 95% CI 16-33) vs 5% positivity threshold (33%, 95% CI 11-68); E1L3N (42%, 95% CI 10-82) vs SP142 antibody (27%, 95% CI 20-36). Conclusions: The discordance in PD-L1 expression between primary tumors and paired distant metastases is close to 30%, which could potentially affect response to immunotherapy. Further works exploring the mechanisms and impact of this discordance are warranted.

Programmed Death Ligand 1 (PD-L1) Expression in Epithelial Ovarian Cancer: A Comparison of Type I and Type II Tumors

Objective:To examine the expression of programmed death ligand 1 (PD-L1) in type I and type II epithelial ovarian cancers (EOC) and its associations with outcomes. Methods:Records of 132 women with EOC were reviewed. Immunostaining of PD-L1 was performed with formalin-fixed, paraffin-embedded specimens. Expression of PD-L1 was classified into four categories (0; 1+; 2+; 3+) according to intensity of expression. Expression of PD-L1 ≥2+ was deemed to be high. Results:Of the 132 women, 75 (56.8%) and 57 (43.2%) women had type I and type II tumors, respectively. Approximately 70% of cases exhibited high PD-L1 expression. There was no significant difference in the rate of high PD-L1 expression between the two EOC types (65.3% versus 59.6%). In type I tumors, high PD-L1 expression was associated with more advanced stages (51.0% versus 34.6%), greater recurrence (46.9% versus 26.9%), and shorter median progression-free survival (27 months versus 62 months) than low expression. In type II tumors, there were no apparent differences between high and low expression of PD-L1 in terms of the percentage of advanced-stage tumors (82.6% versus 79.4%), recurrence (56.5% versus 58.8%), and median progression-free survival (21 months versus 24 months). Conclusion:high PD-L1 expression is associated with worse oncological outcomes in type I EOC. This finding emphasizes the merit of further studies to confirm this promising result and to determine the potential role of PD-L1 blockade therapy in type I EOC.

Imunoterapia no Cancro do Pulmão de Não Pequenas Células Doença Avançada: A Propósito de Dois Casos Clínicos

À luz dos conhecimentos atuais, o tratamento de imunoterapia no cancro do pulmão de não pequenas células doença avançada apresenta os melhores resultados nos doentes com expressão de programmed death ligand 1 (PD-L1) positiva.Apresentamos dois casos clínicos diferentes, ambos de sucesso: o primeiro referente a um doente do sexo masculino, 91 anos, com expressão de PD-L1 de 90% e com elevada taxa de resposta ao tratamento de imunoterapia com pembrolizumab na dose de 200 mg, a cada 3 semanas; no segundo caso trata-se de uma doente do sexo feminino, de 47 anos, com expressão de PD-L1 negativa e em que a imunoterapia foi usada como segunda linha, após se verificar progressão sob tratamento com quimioterapia, tendo-se verificado também neste caso uma resposta completa com o uso de atezolizumab, na dose de 1200 mg, a cada 3 semanas.

PD-L1 expression is related with prognosis of small cell lung cancer

Objective: To explore the correlation between programmed death ligand 1 (PD-L1) expression and clinicopathological features and prognosis of small cell lung cancer (SCLC). Methods: The clinicopathological data of 64 patients with small cell lung cancer from January 2013 to December 2016 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed in this study. The correlation between PD-L1 expression and the clinicopathological features and prognosis of SCLC was analyzed. Results: Immunohistochemical staining revealed that PD-L1 expression was observed in 60.9% (39/64) of patients with small cell lung cancer. PD-L1 expression was significantly related to stages (P<0.001). Univariate analysis showed that the median overall survival of PD-L1 negative group was longer than PD-L1 positive group (16 months vs 14 months, P<0.001). Median progression-free survival of PD-L1 negative group was longer than PD-L1 positive group(15 months vs 9 months, P<0.000 1). In multivariate analysis, PD-L1 positive was significantly correlated with inferior progression-free survival (P=0.006). Conclusions: PD-L1 expression rate was high in small cell lung cancer. PD-L1 expression was an independent predictor for poor prognosis of patients with small cell lung cancer.

Expression and clinical significance of costimulatory molecule B7-H4 and programmed death ligand 1 in bladder cancer

Objective To detect the expression of costimulatory molecules B7-H4 and programmed death ligand 1(PD-L1) in bladder cancer, and to explore the correlation between them and clinicopathological features of bladder cancer. Methods Immunohistochemical staining was used to detect the expression of B7-H4 and PD-L1 in 98 cases of bladder urothelial carcinoma, which were confirmed by pathology from August 2014 to December 2015 in our hospital. There were 23 females, aged 45-82 years, with an average age of 67.8 years. Among them, 42 cases of adjacent normal tissues were used as controls. The clinical stage, histological grade and recurrence of bladder cancer were collected, and the correlation between them was analyzed. Results The positive rates of B7-H4 and PD-L1 in bladder urothelial carcinoma were 54.1% (53/98) and 59.2% (58/98), respectively, and there was no expression in normal bladder tissues (P<0.05). The positive expression rate of B7-H4 in muscle invasive bladder cancer (MIBC) patients was higher than that in non-muscle invasive bladder cancer (NMIBC) [73.5% (25/34) vs. 43.8% (28/64), P=0.005]. The positive expression rate of B7-H4 in high-grade patients was higher than that of low-grade [70.0%(21/30) vs. 47.1%(32/68), P=0.036]. The expression rate of B7-H4 in high-risk group was higher than that of low-intermediate risk group [ 57.1%(20/35) vs. 27.6%(8/29), P=0.018]. The positive expression rate of PD-L1 in patients with MIBC was higher than that in NMIBC [79.4% (27/34) vs. 48.4% (31/64), P=0.003]. The PD-L1 expression rate of histological high-level group was higher than that of low-level group [ 73.3% (22/30) vs. 52.9% (36/68)], but the difference was not statistically significant (P=0.058). The PD-L1 expression rate in high-risk group was 68.6% (24/35), and also higher than low-middle group 24.1% (7/29) (P<0.05). There was a positive correlation between the expression of B7-H4 and PD-L1 in bladder urothelial carcinoma (r=0.318, P=0.002). The combined recurrence rate of the two groups was significantly higher than that of the negative expression of the two groups [66.7% ( 14/21) vs. 30.8% (8/26), P=0.014]. Conclusions The expression of B7-H4 and PD-L1 is up-regulated in bladder urothelial carcinoma, which is closely related to the clinical stage, histological grade, risk classification and recurrence of NMIBC. Key words: Costimulatory molecule; B7-H4; Programmed death-ligand 1; Bladder urothelial carcinoma

Abstract 3927: Clinicopathologic features and immune microenvironment of non-small cell lung cancer with primary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors

Abstract Background: Approximately 20-30% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) activating mutations are not responsive to EGFR-tyrosine kinase inhibitors (TKIs). Although, primary resistance to EGFR-TKI is attributed to various genetic alterations, little is known about the clinical and immunopathological features of patients with primary resistance. The tumor immune microenvironment including tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) has been reported to play an important role in tumor progression in NSCLC. However, few studies have directly focused on the relationship between the tumor immune microenvironment and primary resistance to EGFR-TKI. Materials and Methods: Characteristics of 124 NSCLC patients with EGFR mutations who received EGFR-TKI were analyzed. Primary resistance was defined as disease progression within 3 months after EGFR-TKI treatment. Tumor specimens obtained before EGFR-TKI treatment were assessed for the density of TILs expressing CD4 or CD8, and for the expression rate of PD-L1 on tumor cells and tumor-infiltrating immune cells, immunohistochemically. Results: Primary resistance was observed in 13.7% (17/124) of patients. Smoking Tobacco correlated significantly with primary resistance compared to non-primary resistance. Lower density of total TILs and negative PD-L1 expression as per immunohistochemical analysis correlated significantly with primary resistance. Moreover, immune ignorant phenotype of tumor microenvironment, negative PD-L1 expression with low TIL density, was significantly observed in primary resistance. Conclusions: Smoking and immune ignorance in the tumor microenvironment might result in primary resistance to EGFR-TKIs. Citation Format: Yuta Takashima, Jun Sakakibara-Konishi, Yutaka Hatanaka, Kanako C. Hatanaka, Yoshihito Ohhara, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Yoshihiro Matsuno, Masaharu Nishimura. Clinicopathologic features and immune microenvironment of non-small cell lung cancer with primary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3927.

Expression and clinical significance of programmed death ligand 1 in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) has the highest incidence of all types of head and neck cancer in China. The present study aimed to investigate the association between the expression of programmed death ligand 1 (PD-L1) in NPC tissues and clinicopathological features, as well the outcomes for NPC patients. In addition, the association between tissue expression of PD-L1 and immune components in peripheral blood was assessed. The expression of PD-L1 was determined by immunohistochemistry, while immune indexes were determined by ELISA and flow cytometry. The positive expression rate of PD-L1 in NPC patients was 29.2%, and the PD-L1 expression levels were associated with distant metastasis (P=0.010) and the T-stage of the primary tumor (P=0.032). The expression of PD-L1 was associated with the distant metastasis-free survival of NPC patients (P=0.006). In addition, a statistically significant association of PD-L1 expression with Epstein-Barr virus viral capsid antigen IgA (EBV VCA-IgA; P=0.046) and with CD3-CD19+ cells (P=0.014) was identified. These results indicated that PD-L1 may be a potential prognostic biomarker for NPC patients, and that EBV VCA-IgA and CD3-CD19+ cells may be useful for predicting PD-L1 expression when its levels cannot be detected due to the lack of a tumor tissue sample.

Clonality analysis of synchronous gastro-oesophageal junction carcinoma and distal gastric cancer by whole-exome sequencing.

Gastro-oesophageal junction (GEJ) carcinoma and distal gastric cancer (GC) have distinct epidemiology and clinical features and their relationship is uncertain. Synchronous multiple gastric cancers located mostly at proximal and distal sites provide rare specimens for investigating the comprehensive genomic relationships among these cancers in the context of identical genetic circumstances. Formalin-fixed, paraffin-embedded (FFPE) samples from 12 patients with synchronous GEJ carcinoma and distal GC were collected in this study. Whole-exome sequencing (WES) was performed using normal tissues as a control. Mutational profiling, clonality analysis, a detailed clinico-pathological review, determination of MSI status, EBER in situ hybridization (ISH), and programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunohistochemical staining were performed. Twenty-three of the 24 samples were microsatellite-stable (MSS). Subclonal analysis revealed that nine pairs of GEJ and distal GC tumours in neoadjuvant chemotherapy naïve patients developed independently from different origins. Two patients who received neoadjuvant chemotherapy shared clonal origins with highly similar somatic alterations. The remaining one patient who shared a rare mutation died within 6.2 months at the N3 stage. However, the enriched pathway identified from the overall mutation spectra in distal GC and GEJ carcinoma showed the close relationship of these cancers. Thus, although these cancers may have similar characteristics, histopathological and genetic profiling from single tumour specimens may still underestimate the mutational burden and somatic heterogeneity of multiple GCs. In addition, this series of cases also showed a PD-L1 expression rate of 58.3% and 66.7% in distal GC and GEJ carcinoma, respectively, with all the cases expressing PD-1. This result suggests the potential benefit of immunotherapeutic treatments. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Predictive role of PD-L1 expression in the response of renal Medullary carcinoma to PD-1 inhibition

BackgroundRenal medullary carcinoma is one of the rarest malignancies arising from the kidney. Despite various aggressive therapeutic regimens, mortality remains significantly high (95%) with a median overall survival of 5 months. Furthermore, the scarcity of this malignancy renders randomized clinical trials impossible. We examined the expression of programmed death ligand 1 (PD-L1) in two new renal medullary carcinoma cases, investigated their responses to the PD-L1 inhibitor nivolumab and explored the predictive role of the rate of PD-L1 expression in such response.Case presentationTwo African-American patients (male and female) with sickle cell trait who presented to our center with hematuria and flank pain were diagnosed with metastatic renal medullary carcinoma. PD-L1 was expressed at rate of 25% and 60% in patient 1 and 2 respectively. Following nephrectomy, they were started on nivolumab. Patient 1 initially responded to the treatment with regression of metastatic lesions. However, following this early response, patient 1 who has been receiving nivolumab for more than 15 months, was noted to have a disease progression. Patient 2 had disease progression after 3 months of nivolumab therapy.ConclusionsAlthough PD-L1 is expressed in these patients with renal medullary carcinoma, response to nivolumab was only observed in patient 1 whose tumor has the lowest rate of PD-L1 expression. This may suggest that in RMC, response to PD-L1 inhibition therapy may not correlate with the rate of PD-L1 expression.

Relationship between expression of PD-L1 and tumor angiogenesis, proliferation, and invasion in glioma.

Programmed death ligand 1 (PD-L1) is highly expressed in many cancers. We investigated the expression of PD-L1 and its relationship with vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 and KI-67 expression in 64 patients with primary glioma. The expression rate of PD-L1 in glioma patients was 78.12%. PD-L1 levels correlated with the tumor grade (p = 0.013), VEGF status (p = 0.002) and KI-67 status (p = 0.002). In addition, PD-L1 levels correlated positively with VEGF (r = 0.314, p = 0.011) and KI-67 (r = 0.391, p = 0.001) levels when the data were treated as continuous variables. This is the first report suggesting that PD-L1 is important for glioma angiogenesis and proliferation. Thus, further research should be conducted to assess the combination of targeted VEGF therapy and anti-PD-L1 immunotherapy for the treatment of glioma.

Expression of programmed death-ligand 1, topoisomerase IIα and p16 proteins in cervical cancer and their significances

Objective To analyze the expression of programmed death ligand 1 (PD-L1), p16 proteins and DNA topoisomerase Ⅱα (TOPOⅡα) in cervical cancer and their clinical significances. Methods A total of 181 paraffin-embedded operating specimens and the biopsy including 106 cervical squamous cell carcinoma, 30 high grade cervical intraepithelial neoplasia (CIN), 30 low grade CIN and 33 normal cervical were selected from January 2014 to December 2015. An immunohistochemical EnVision method was used to detect the expression of PD-L1, p16 and TOPOⅡα. Results The positive rate of PD-L1 expression in cervical squamous cell carcinoma was 66.0% (70/106), but it was not expressed in high grade CIN, low grade CIN and normal cervical tissues, the differences were statistically significant (all P= 0.000). Whereas, in squamous cell carcinoma, the positive rate of PD-L1 in poor differentiation group [77.3% (51/66)] was higher than that in middle or high differentiation group [56.5% (21/40)], and the difference was statistically significant (χ2= 7.02,P= 0.01). According to the FIGO stage, the positive rate in stage Ⅰ-Ⅱ group [54.9% (28/51)] was lower than that in stage Ⅲ-Ⅳ group [76.4% (42/55)], and the difference was statistically significant (χ2= 5.47, P= 0.02). But there was no statistical significance in lesion size or lymph node metastasis (both P > 0.05). The positive rate of p16 in cervical squamous cell carcinoma was 99.1% (105/106), in high grade CIN was 86.7% (26/30), in low grade CIN was 26.7% (8/30), and no expression in normal cervical tissues, the differences were statistically significant (all P 0.05). The positive expression rate of TOPOⅡα in cervical squamous cell carcinoma was 97.2% (103/106), compared with that in high grade CIN [73.3% (22/30)], low grade CIN [66.7% (20/30)], and normal cervical tissues (no expression), the differences were statistically significant (all P= 0.000). But there was no significant difference in the positive expression rate of TOPO Ⅱα between high grade and low grade CIN (χ2= 0.32, P= 0.570). The expression of TOPOⅡα had no relationship with histological differentiation, FIGO stage, lesion size and lymph node metastasis (all P > 0.05). Conclusion The expression of PD-L1, p16 and TOPOⅡα is associated with the invasion of cervical cancer.PD-L1 may be an immune checkpoint for the treatment of patients with invasive cervical cancer. Key words: Uterine cervical neoplasms; DNA topoisomerases, type Ⅱ; Programmed death ligand 1; Genes, p16

Correlation of PD-L1 with VEGF and KI-67 index in patients with primary glioma.

94 Background: The treatment strategies for glioma, especially glioblastoma multiforme, are not effective. The programmed death ligand 1 (PD-L1) immune escape and increased angiogenesis may be two of the underlying sources of treatment resistance. However, the relationship between these pathways in human glioma is still unknown. Methods: Data for 64 patients with primary glioma recorded from June 2007 to December 2013 in Shan Dong Cancer Hospital were immunohistochemically evaluated for the expressions of PD-L1, VEGF, MMP-9 and KI-67 index. Image ProPlus software was used to quantify the mean optical density (MOD) of the immunohistochemical image. Results: PD-L1 expression was observed in 65.22% of low-grade glioma and 90.24% of high-grade glioma, respectively. The whole expression rate of PD-L1 in glioma was 81.25%. The expression of PD-L1 is significantly related to pathological grade ( p &lt;0.001), VEGF ( p= 0.017) and KI-67 index ( p= 0.009). The mean of PD-L1 MOD in High-grade group was 0.1144±0.02754, higher than that in low-grade group, 0.005129±0.001441 ( p= 0.004). In addition, Expression of VEGF, MMP-9 and KI-67 was significantly different between low-grade and high-grade gliomas ( p= 0.008, 0.04, 0.004 for VEGF, MMP-9 and KI-67, respectively). When analyzed as a continuous variable, the expressions of PD-L1 was positively correlated with VEGF (r = 0.392, p= 0.001) and KI-67 (r = 0.388, p= 0.001). Conclusions: These data suggest, for the first time, that PD-L1 play an important role in glioma angiogenesis and proliferation potential, providing the possibility for considering additional combinations of targeted VEGF therapies and anti-PD-L1 immunotherapy for the treatment of human brain glioma.

Prognostic significance of programmed death-1 and programmed death-ligand 1 expression in patients with esophageal squamous cell carcinoma.

AimsTo evaluate the expression of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) and their clinical and prognostic significance in primary esophageal squamous cell carcinoma (ESCC).ResultsThe expression rate of PD-1 and PD-L1 in ESCC was 33.5% (117/349) and 41.4% (222/536), respectively. PD-L1 expression differed significantly by tumor location, grade, lymph node metastases, and disease stage (P < 0.05). Moreover, its expression was associated with the disease free survival (DFS). Patients with positive PD-L1 expression had reduced risk for disease relapse compared to those without PD-L1 expression (Hazard ratio [HR] = 0.75, 95% confidence interval [CI]: 0.56–1.00, P = 0.048). Kaplan-Meier curves showed the similar result, P = 0.047. However, there was no significant correlation between PD-1 expression and clinicopathological factors or outcome in ESCC (P > 0.05).MethodsThe expression of PD-1 and PD-L1 was assessed by immunohistochemistry on tissue microarrays from 536 primary ESCC who underwent surgery during January 2008 and April 2012 in Zhejiang Cancer Hospital. Chi-square test and Cox proportional hazards regression were employed to analyze the associations between their expressions and clinicopathological variables and survival.ConclusionsOur results suggested that PD-L1 could be a favorable indicator of prognosis in ESCC.

The prevalence and clinicopathological features of programmed death-ligand 1 (PD-L1) expression: a pooled analysis of literatures.

Background & AimsProgrammed death-ligand 1 (PD-L1) has been recognized as a critical and promising target in therapies that direct immune escape of cancers. However, its association with aggressive clinicopathological features in solid tumors remains unclear. We investigated this question by synthesizing published articles.MethodsElectronic databases were searched for relevant studies. Outcomes of interest included age, gender, tumor size, tumor size, lymph node metastasis and tumor cell differentiation.ResultsA total of 61 studies involving 17 types of malignancies were included. The overall expression rate of PD-L1 was 44.5% (95% CI, 37.5% to 51.6 %). Patients with regional lymph node metastases (OR 1.38; P < 0.01), large size tumor (OR 1.89; P < 0.01) or poor differentiated tumors (OR 1.71; P < 0.01) were associated with higher PD-L1 expression rate. However, no significant association was observed between young and elder patients (OR 1.04; P = 0.58), or male and female patients (OR 1.13; P = 0.06). A numerically higher PD-L1 expression rate was detected in polyclonal antibodies (57.2%) than monoclonal antibodies (39.6%). In addition, the PD-L1 expression rate reported by studies from Asian areas (52.3%) was numerically higher than those from non-Asian areas, namely Caucasians (32.7%).ConclusionsThis meta-analysis indicated that patients with larger tumors, regional lymph node metastases, or poor-differentiated tumors were associated with a higher PD-L1 expression rate; in addition the expression rate of PD-L1 in Asians might be higher than that of Caucasians. This information might be useful in screening candidates for relevant tests and treatments.