scholarly journals Harmonization of PD-L1 Immunohistochemistry and mRNA Expression Scoring in Metastatic Melanoma: A Multicenter Analysis

2021 ◽  
Author(s):  
Marie Darmon-Novello ◽  
Julien Adam ◽  
Laurence Lamant ◽  
Maxime Battistella ◽  
Nicolas Ortonne ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Intraclass Correlation ◽  
Daily Practice ◽  
Programmed Death ◽  
Multicenter Analysis ◽  
Positive Score ◽  
Specimen Quality ◽  
Standardized Method ◽  
Good Concordance ◽  
Combined Positive Score

Abstract Background: Melanoma is a type of cancer with robust response to immunotherapy. Programmed death ligand 1 (PD-L1) testing is not required to treat patients, but most studies have demonstrated correlations between PD-L1 expression and treatment response using various assays and scoring methods. This multicenter study aimed to harmonize PD-L1 immunohistochemistry (IHC) and scoring in melanoma. To provide a reference for PD-L1 expression independent of the IHC protocol, PD-L1 mRNA expression was determined via RNAscope, then compared to IHC.Methods: Standardized PD-L1 assays (22C3, 28–8, SP142, and SP263) and laboratory-developed tests (clone QR1 and 22C3) were evaluated on three IHC platforms using a training set of 7 cases. mRNA expression was determined via RNAscope (CD274/PD-L1 probe) and analyzed by image analysis. PD-L1 IHC findings were scored by seven blinded pathologists using the tumor proportion score (TPS), combined positive score (CPS), and MELscore. After the study, a standardized method was proposed; this was validated by three blinded pathologists on a set of 40 metastatic melanomas that were stained using three protocols.Results: Concordances among various antibody/platforms were high across antibodies (e.g., intraclass correlation coefficient [ICC] > 0.80 for CPS), except for SP142. Two levels of immunostaining intensities were observed: high (QR1 and SP263) and low (28–8, 22C3, and SP142). Reproducibilities across pathologists were higher for QR1 and SP263 (ICC ≥ 0.87 and ≥ 0.85 for TPS and CPS, respectively). QR1, SP263, and 28-8 showed the highest concordance with mRNA expression (ICC ≥ 0.81 for CPS). Accordingly, we proposed a standardized method for PD-L1 immunodetection and scoring, then tested it on 40 metastatic melanomas. This method included analysis of specimen quality (e.g., host-tumor interface and pigmentation). Concordances among antibodies were excellent for all criteria, and concordances among pathologists were better for the MELscore than for other scores.Conclusion: Harmonization of PD-L1 staining and scoring in melanomas with good concordance is achievable using the PD-L1 IHC protocols applied to other cancers; this reproducible approach can simplify daily practice. Our proposal for a PD-L1 standardized methodology has higher reproducibility across pathologists for clinical and research use.

Molecular comparison between peritoneal metastases (PM) and primary gastric (GC) and gastroesophageal junction (GEJ) cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4053-4053
Author(s):  
Matthew K Stein ◽  
Joanne Xiu ◽  
Michael Gary Martin ◽  
Axel Grothey ◽  
Philippe Prouet ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Programmed Death ◽  
Signet Ring ◽  
Tumor Mutational Burden ◽  
Molecular Comparison ◽  
Positive Score ◽  
The Mean ◽  
Combined Positive Score ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

4053 Background: PM from GC or GEJ portend a poor prognosis and molecular differences are ill defined. Methods: We compared genomic profiles of primary (P) GC and GEJ with PM patients (pts) and other metastases (OM) sent to Caris Life Sciences. Testing comprised immunohistochemistry (IHC) including programmed death ligand 1 (PD-L1) combined positive score (CPS), copy number alterations (CNA), 592-gene next-generation sequencing (NGS), microsatellite instability (MSI) and tumor mutational burden (TMB). Results: 1366 cases were identified: 1041 GC (707 P, 98 PM, 236 OM) and 325 GEJ (248 P, 5 PM, 72 OM). PM were increased in GC versus GEJ (9% v. 2%, p < 0.0001). 91% GC and 93% GEJ were adenocarcinoma (AD); GC were more likely signet ring (SR) histology versus GEJ (11% v. 3%, p < 0.0001) and GC PM were more likely SR versus other OM or P (13% v. 12% v. 7%, p = 0.067). The mean age of PM pts (57 years) was younger than primary GC (63, p = 0.002) and OM (61; p = 0.044). More PM GC pts were female than P or OM (48% v. 35% v. 34%, p = 0.03). No molecular profiling differences were seen between GEJ and GC pts and they were combined for analysis; findings from 1246 AD pts are shown below (see Table). OM (9%, p = 0.041) had more CNA in CCNE1 than PM (2%, p = 0.041) or P (5%, p = 0.002). Conclusions: Compared to P and OM GC, PM pts were younger, more likely female and had a higher incidence of SR histology. PD-L1, HER2 IHC and ERBB2 CNA were reduced in PM versus P, suggesting novel therapeutic targets are needed. [Table: see text]

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 &lt; .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.

812 PROGRAMMED CELL DEATH PROTEIN 1/PROGRAMMED DEATH LIGAND 1 AND HLA-CLASS I ARE POTENTIAL THERAPEUTIC TARGETS IN ESOPHAGEAL NEUROENDOCRINE CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Satoshi Ya Masthita ◽  
Hiroyuki Abe ◽  
Hiroharu Yamashita ◽  
Koichi Yagi ◽  
Yasuyuki Seto ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Therapeutic Targets ◽  
Tumor Infiltrating Lymphocytes ◽  
Hla Class I ◽  
Class I ◽  
Neuroendocrine Neoplasm ◽  
Programmed Death ◽  
Positive Score ◽  
Combined Positive Score ◽  
Infiltrating Lymphocytes

Abstract   Esophageal neuroendocrine carcinoma (NEC) is a rare and aggressive subtype with a poor prognosis. Pembrolizumab was recommended for the treatment of PD-L1 positive tumors in esophageal cancer and the combined positive score (CPS) was reported to be a better predictor of efficacy compared to the tumor proportion score (TPS). We investigated the expression profile of potential therapeutic targets (PD-L1, HLA class I, Mismatch repair (MMR) proteins) and tumor infiltrating lymphocytes (TILs) in esophageal NEC. Methods 15 NECs of the esophagus including mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) with squamous cell carcinoma (SCC) component were investigated in the study. The expression of PD-L1 (quantitatively evaluated by CPS and TPS), HLA class I, and MMR protein expression were examined immunohistochemically. TIL abundance was examined semiquantitatively by observation of H&E slides. Results Nine (60%) showed a CPS ≥ 1, five (33%) showed a CPS ≥10, and five cases showed a TPS ≥1. Survival analysis showed a significantly longer overall survival in the CPS ≥1 group than in the CPS &lt;1 group. Deficiency of MMR protein was not observed in any cases. HLA-Class I expression was retained in 10 (67%), and loss of HLA-Class I was significantly correlated with frequent lymph node metastasis, high TNM Stage, and low TIL. Three showed both PD-L1 CPS ≥ 10 and high TIL. Conclusion In esophageal NEC, PD-L1 positivity and preserved HLA-Class I expression were frequently observed, and PD-L1 CPS ≥ 1 was significantly associated with the better prognosis of esophageal NEC. Therefore, the PD-1/PD-L1 pathway and HLA-class I are thought to be potential therapeutic targets in esophageal neuroendocrine carcinoma.

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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