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

2021 ◽  
Author(s):  
Ashley L. Monsrud ◽  
Vaidehi Avadhani ◽  
Marina B. Mosunjac ◽  
Lisa Flowers ◽  
Uma Krishnamurti
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Viral Load ◽  
Hiv Status ◽  
Hiv Viral Load ◽  
Anal Squamous Cell Carcinoma ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Positive Score ◽  
Combined Positive Score

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.

PD-L1 Expression is Associated with Poorer Survival in Anal Squamous Cell Carcinoma: Analysis from an Urban Public Hospital

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S66-S67
Author(s):  
A Monsrud ◽  
V Avadhani ◽  
M Mosunjac ◽  
U Krishnamurti
Keyword(s):  
Squamous Cell Carcinoma ◽  
Viral Load ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cd4 Count ◽  
Hiv Status ◽  
Hiv Viral Load ◽  
Cancer Specific Survival ◽  
Anal Squamous Cell Carcinoma ◽  
Cox Regression Analysis

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.

scholarly journals Association of programmed death ligand 1 expression with prognosis among patients with ten uncommon advanced cancers

2020 ◽  
Vol 6 (8) ◽  
pp. FSO616
Author(s):  
Torben Steiniche ◽  
Morten Ladekarl ◽  
Jeanette Bæhr Georgsen ◽  
Simon Andreasen ◽  
Michael Busch-Sørensen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Value ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Positive Score ◽  
Combined Positive Score ◽  
First Line Treatment

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.

scholarly journals PD-L1 Testing in Gastric Cancer by the Combined Positive Score of the 22C3 PharmDx and SP263 Assay with Clinically Relevant Cut-offs

2020 ◽  
Vol 52 (3) ◽  
pp. 661-670 ◽  
Author(s):  
Yujun Park ◽  
Jiwon Koh ◽  
Hee Young Na ◽  
Yoonjin Kwak ◽  
Keun-Wook Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Interobserver Variability ◽  
Tissue Microarrays ◽  
High Agreement ◽  
Programmed Death Ligand 1 ◽  
Positive Expression ◽  
Percent Agreement ◽  
Programmed Death ◽  
Positive Score ◽  
Combined Positive Score

Purpose We provide a comparison between 22C3 pharmDx and SP263 assay, for evaluating programmed death ligand 1 (PD-L1) expression in advanced gastric cancer (GC) patients.Materials and Methods The PD-L1 immunohistochemistry by 22C3 pharmDx and SP263 assays was performed in the center of the tumor (CT) and invasive margin (IM) in 379 GC tissues using tissue microarrays and interpreted as combined positive score (CPS) and tumor proportion score (TPS). Of the total samples, 55 samples were independently reviewed by five pathologists.Results The two assays showed a high correlation in both the CPS and TPS. At a CPS ≥ 1 cut-off, 219 (57.8%) and 231 (60.9%) GCs were positive for PD-L1 with the 22C3 and SP263 assays, and at ≥ 10 cut-off, 37 (9.8%) and 36 (9.5%) GCs were positive, respectively. The overall percent agreement (OPA) was greater than 90% with CPS ≥ 1 and ≥ 10 cut-offs, and TPS ≥ 1% and ≥ 10% cut-offs. There was higher OPA between the two assays with a CPS cut-off ≥ 10 (99.2%) than ≥ 1 (94.7%). The percent agreement between the CT and IM was higher with a CPS cut-off ≥ 10 (92.9%) than ≥ 1 (77.6%). Patient with positive expression at CPS ≥ 5 cut-off had a significantly better outcomes in both assays. Interobserver variability among five pathologists was higher than the assay variability.Conclusion Two assays for PD-L1 expression in GC showed high agreement. These results provide guidance for selecting eligible patients with GC for pembrolizumab treatment.

scholarly journals Simultaneous upper and lower urinary tract invasive Lymphoepithelioma-like carcinoma with programmed death-ligand 1 full expression on combined positive score

2020 ◽  
Vol 31 ◽  
pp. 101201
Author(s):  
Che-Hsueh Yang ◽  
Yi-Sheng Lin ◽  
Wei-Chun Weng ◽  
Yen-Chuan Ou ◽  
Chao-Yu Hsu ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Lower Urinary Tract ◽  
Programmed Death Ligand 1 ◽  
Full Expression ◽  
Programmed Death ◽  
Positive Score ◽  
Combined Positive Score ◽  
Lower Urinary

Programmed Death Ligand 1 Expression and Related Markers in Pleuropulmonary Blastoma

2021 ◽  
pp. 109352662110274
Author(s):  
Zahra Alipour ◽  
Kris Ann P Schultz ◽  
Ling Chen ◽  
Anne K Harris ◽  
Ivan A Gonzalez ◽  
...  
Keyword(s):  
Metastatic Tumor ◽  
Pleuropulmonary Blastoma ◽  
Type I ◽  
Type Ii ◽  
Programmed Death Ligand 1 ◽  
Dna Mismatch ◽  
Programmed Death ◽  
Tumor Mutational Burden ◽  
Positive Score ◽  
Combined Positive Score

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.

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