scholarly journals Programmed Death Ligand-1 Expression Is Associated With Poorer Survival in Anal Squamous Cell Carcinoma

Author(s):  
Ashley L. Monsrud ◽  
Vaidehi Avadhani ◽  
Marina B. Mosunjac ◽  
Lisa Flowers ◽  
Uma Krishnamurti

Context.— Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in invasive anal squamous cell carcinoma (ASCC). Objective.— To assess PD-L1 expression in patients with ASCC and correlate it with clinicopathologic factors and clinical outcomes. Design.— Fifty-one cases of ASCC were immunostained for PD-L1. PD-L1 expression by combined positive score and tumor proportion score was correlated with age, gender, HIV status, HIV viral load, CD4 count, stage, and outcomes. Kaplan-Meier curves for overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P < .05 was considered statistically significant). Results.— PD-L1 was positive in 24 of 51 cases (47%) by combined positive score and in 18 of 51 (35%) by tumor proportion score. The median cancer-specific survival and 5-year overall survival were significantly lower in PD-L1+ patients. Age, gender, HIV status, HIV viral load, stage, and cancer progression were not significantly different between the two groups. CD4 count of more than 200/μL was significantly higher in PD-L1+ patients. PD-L1+ status remained statistically significant for worse overall survival on multivariate analysis. Conclusions.— PD-L1+ status is an independent adverse prognostic factor for overall survival in ASCC. This study highlights the potential of PD-L1 targeted therapy in better management of ASCC.

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S66-S67
Author(s):  
A Monsrud ◽  
V Avadhani ◽  
M Mosunjac ◽  
U Krishnamurti

Abstract Introduction/Objective Upregulation of programmed death-ligand 1 (PD-L1), an immunoregulatory protein is associated with adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in anal squamous cell carcinoma. This study aims to correlate PD-L1 expression with clinicopathologic factors and clinical outcomes. Methods After IRB approval, formalin-fixed, paraffin embedded sections of 58 cases of anal invasive squamous cell carcinoma from 2010–2018 were immunostained for PD-L1 (Dako 22C3 monoclonal antibody). Of these, 51 cases could be evaluated for PD-L1 expression. Greater than 1% of tumor cells with partial or complete membrane staining was interpreted as PD-L1 positive (PD-L1 +). PD-L1 expression was correlated with age, sex, stage, HIV status, HIV viral load, CD4 count, disease progression, and cancer specific survival. Kaplan-Meier curves for overall survival (OS) were plotted and compared using the log rank test. Cox regression analysis was performed to identify significant prognostic factors (Two-tailed p< 0.05 was considered statistically significant). Results Of the 51 cases evaluated, PD-L1 was positive in 18/51 (35%) and negative in 33/51 (65%) cases. The median cancer specific survival (MCSS) was lower in PD-L1 positive cases (22 months) compared with PD-L1 negative cases (48 months), p=0.008. The number of cancer specific deaths was higher in the PD-L1 + group (50% vs. 30%), but not statistically significant (p= 0.23). Other factors that were not significantly different between the two groups were age, sex, stage, HIV status, HIV viral load, and number of patients with cancer progression. Patients with positive PD-L1 had worse OS (5yr OS: 41% for PD-L1 positive vs 64% for PD-L1 negative; p=0.02). On multivariate analysis, PD-L1 positive status remained statistically significant for worse OS, HR = 6.5 (95% CI 1.2–33.9), p=0.027. Conclusion The median cancer specific survival and 5-yr OS is significantly lower in the PD-L1 positive group. PD-L1 positive status is associated with a worse prognosis independent of stage, HIV status, HIV viral load, and CD4 count. The study highlights the potential of PD-L1 targeted therapy in better management of anal squamous cell carcinoma.


2020 ◽  
Vol 6 (8) ◽  
pp. FSO616
Author(s):  
Torben Steiniche ◽  
Morten Ladekarl ◽  
Jeanette Bæhr Georgsen ◽  
Simon Andreasen ◽  
Michael Busch-Sørensen ◽  
...  

Aim: PD-L1 expression and high levels of microsatellite instability (MSI-H) may predict response to checkpoint inhibitors, but their prevalence and prognostic value are unknown in many cancers. Methods: We retrospectively evaluated PD-L1 combined positive score (CPS) and MSI-H and their association with clinical outcomes among patients with ten advanced uncommon cancers. Results: 398 of 426 patients (93%) had a valid PD-L1 result; most (242; 61%) had CPS ≥1. Prevalence of MSI-H tumors was 8/360. Median overall survival was shorter among patients with PD-L1 CPS ≥1 tumors after first-line treatment (23.0 vs 39.7 months, p = 0.014). Conclusion: PD-L1 was commonly expressed in solid tumors, and CPS ≥1 was associated with shorter overall survival. Prevalence of MSI-H was low.


2021 ◽  
pp. 109352662110274
Author(s):  
Zahra Alipour ◽  
Kris Ann P Schultz ◽  
Ling Chen ◽  
Anne K Harris ◽  
Ivan A Gonzalez ◽  
...  

Introduction Pleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic DICER1 variants. We investigated checkpoint inhibitor markers including Programmed Death Ligand 1 (PD-L1), PD1, CD8 and tumor mutational burden (TMB) in PPB. Material and Methods Cases were collected from departmental archives and the International PPB/ DICER1 Registry. Immunohistochemistry (IHC) for PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) genes were performed. In addition, normal-tumor paired whole exome sequencing (WES) was performed in two cases. Results Twenty-five PPB cases were studied, consisting of Type I (n = 8, including 2 Ir), Type II (n = 8) and Type III (n = 9). PD-L1 combined positive score (CPS) of 1, 4 and 80 was seen in three (3/25, 12.0%) cases of Type II PPB with negative staining in the remaining cases. PD-1 and CD8 stains demonstrated positive correlation ( P < .05). The density of PD1 and CD8 in the interface area was higher than within tumor ( P < .05). The MMR proteins were retained. TMB was 0.65 mutations/Mb in type II PPB with high expression of PD-L1, and 0.94 mutations/Mb in one negative PD-L1 case with metastatic tumor. Conclusion A small subpopulation of PPB patient might benefit from checkpoint immunotherapy due to positive PD-L1 staining.


2020 ◽  
Vol 13 ◽  
pp. 2632010X2096484
Author(s):  
Sebnem Batur ◽  
Zeynep Ecem Kain ◽  
Emine Deniz Gozen ◽  
Nuray Kepil ◽  
Ovgu Aydin ◽  
...  

Aim: We aimed to show the immunohistochemical expression of programmed death ligand 1 (PD-L1) in laryngeal squamous cell carcinomas (SCCs). Materials and methods: The study includes 52 laryngeal SCC cases that underwent surgical resection. Immunohistochemical staining of PD-L1 (Clone 22C3) was applied to the sections obtained from paraffin blocks. Combined Positive Score (CPS) was evaluated as described in manuals. Tumor Proportion Score (TPS) was assessed by the percentage of positive tumor cells which were designated as positive if ⩾1% of the tumor cells showed membranous staining. Results: There were 35 cases (67.3%) having CPS < 1 and 17 cases (32.7%) having CPS ⩾ 1. There was no relationship between CPS, TPS, and the clinicopathological data. Conclusion: Further studies with a large number of advanced-stage cases are needed.


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