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Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms
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- Sigurjonsdottir, Gudbjörg (författare)
- Lund University,Lunds universitet,Medicinsk onkologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Bröstcancer Proteogenomik,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Medical oncology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Breast cancer Proteogenomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
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- De Marchi, Tommaso (författare)
- Lund University,Lunds universitet,Medicinsk onkologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Bröstcancer Proteogenomik,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Medical oncology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Breast cancer Proteogenomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Region Skåne
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- Ehinger, Anna (författare)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Region Skåne
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- 2023
- 2023
- Engelska.
- Ingår i: Breast Cancer Research. - 1465-5411 .- 1465-542X. ; 25:1
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Background: Immunohistochemical (IHC) PD-L1 expression is commonly employed as predictive biomarker for checkpoint inhibitors in triple-negative breast cancer (TNBC). However, IHC evaluation methods are non-uniform and further studies are needed to optimize clinical utility. Methods: We compared the concordance, prognostic value and gene expression between PD-L1 IHC expression by SP142 immune cell (IC) score and 22C3 combined positive score (CPS; companion IHC diagnostic assays for atezolizumab and pembrolizumab, respectively) in a population-based cohort of 232 early-stage TNBC patients. Results: The expression rates of PD-L1 for SP142 IC ≥ 1%, 22C3 CPS ≥ 10, 22C3 CPS ≥ 1 and 22C3 IC ≥ 1% were 50.9%, 27.2%, 53.9% and 41.8%, respectively. The analytical concordance (kappa values) between SP142 IC+ and these three different 22C3 scorings were 73.7% (0.48, weak agreement), 81.5% (0.63) and 86.6% (0.73), respectively. The SP142 assay was better at identifying 22C3 positive tumors than the 22C3 assay was at detecting SP142 positive tumors. PD-L1 (CD274) gene expression (mRNA) showed a strong positive association with all two-categorical IHC scorings of the PD-L1 expression, irrespective of antibody and cut-off (Spearman Rho ranged from 0.59 to 0.62; all p-values < 0.001). PD-L1 IHC positivity and abundance of tumor infiltrating lymphocytes were of positive prognostic value in univariable regression analyses in patients treated with (neo)adjuvant chemotherapy, where it was strongest for 22C3 CPS ≥ 10 and distant relapse-free interval (HR = 0.18, p = 0.019). However, PD-L1 status was not independently prognostic when adjusting for abundance of tumor infiltrating lymphocytes in multivariable analyses. Conclusion: Our findings support that the SP142 and 22C3 IHC assays, with their respective clinically applied scoring algorithms, are not analytically equivalent where they identify partially non-overlapping subpopulations of TNBC patients and cannot be substituted with one another regarding PD-L1 detection. Trial registration The Swedish Cancerome Analysis Network - Breast (SCAN-B) study, retrospectively registered 2nd Dec 2014 at ClinicalTrials.gov; ID NCT02306096.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- 22C3
- Concordance
- Gene expression
- Immunohistochemistry
- Patient outcome
- PD-L1
- SP142
- TILs
- Triple-negative breast cancer
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- ref (ämneskategori)
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