Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors
Abstract Background In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring method...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-06-01
|
| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-020-01303-9 |
| _version_ | 1819117114865221632 |
|---|---|
| author | Hua Guo Qingqing Ding Yun Gong Michael Z. Gilcrease Min Zhao Jun Zhao Dawen Sui Yun Wu Hui Chen Hui Liu Jinxia Zhang Erika Resetkova Stacy L. Moulder Wei-Lien Wang Lei Huo |
| author_facet | Hua Guo Qingqing Ding Yun Gong Michael Z. Gilcrease Min Zhao Jun Zhao Dawen Sui Yun Wu Hui Chen Hui Liu Jinxia Zhang Erika Resetkova Stacy L. Moulder Wei-Lien Wang Lei Huo |
| author_sort | Hua Guo |
| collection | DOAJ |
| description | Abstract Background In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant. Methods Using FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors. Results In the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups. Conclusions Our findings indicate that the three scoring methods with a 1% cutoff are different in their sensitivity for PD-L1 expression and their associations with clinicopathologic factors. Scoring by TCIC is the most sensitive way to identify PD-L1-positive breast cancer by immunohistochemistry. As a prognostic marker, our study suggests that PD-L1 is associated with worse clinical outcome, most often shown by the IC score; however, the other scores may also have clinical implications in some subgroups. Large clinical trials are needed to test the similarities and differences of these scoring methods for their predictive values in anti-PD-1/PD-L1 therapy. |
| first_indexed | 2024-12-22T05:27:50Z |
| format | Article |
| id | doaj.art-29a330368cbc48e28aed14ab596d3b71 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-22T05:27:50Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-29a330368cbc48e28aed14ab596d3b712022-12-21T18:37:32ZengBMCBreast Cancer Research1465-542X2020-06-0122111810.1186/s13058-020-01303-9Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factorsHua Guo0Qingqing Ding1Yun Gong2Michael Z. Gilcrease3Min Zhao4Jun Zhao5Dawen Sui6Yun Wu7Hui Chen8Hui Liu9Jinxia Zhang10Erika Resetkova11Stacy L. Moulder12Wei-Lien Wang13Lei Huo14Department of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Biostatistics, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Pathology, The University of Texas MD Anderson Cancer CenterAbstract Background In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant. Methods Using FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors. Results In the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups. Conclusions Our findings indicate that the three scoring methods with a 1% cutoff are different in their sensitivity for PD-L1 expression and their associations with clinicopathologic factors. Scoring by TCIC is the most sensitive way to identify PD-L1-positive breast cancer by immunohistochemistry. As a prognostic marker, our study suggests that PD-L1 is associated with worse clinical outcome, most often shown by the IC score; however, the other scores may also have clinical implications in some subgroups. Large clinical trials are needed to test the similarities and differences of these scoring methods for their predictive values in anti-PD-1/PD-L1 therapy.http://link.springer.com/article/10.1186/s13058-020-01303-9PD-L122C3ImmunohistochemistryScoring methodsBreast cancerTumor-infiltrating lymphocytes |
| spellingShingle | Hua Guo Qingqing Ding Yun Gong Michael Z. Gilcrease Min Zhao Jun Zhao Dawen Sui Yun Wu Hui Chen Hui Liu Jinxia Zhang Erika Resetkova Stacy L. Moulder Wei-Lien Wang Lei Huo Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors Breast Cancer Research PD-L1 22C3 Immunohistochemistry Scoring methods Breast cancer Tumor-infiltrating lymphocytes |
| title | Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors |
| title_full | Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors |
| title_fullStr | Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors |
| title_full_unstemmed | Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors |
| title_short | Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors |
| title_sort | comparison of three scoring methods using the fda approved 22c3 immunohistochemistry assay to evaluate pd l1 expression in breast cancer and their association with clinicopathologic factors |
| topic | PD-L1 22C3 Immunohistochemistry Scoring methods Breast cancer Tumor-infiltrating lymphocytes |
| url | http://link.springer.com/article/10.1186/s13058-020-01303-9 |
| work_keys_str_mv | AT huaguo comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT qingqingding comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT yungong comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT michaelzgilcrease comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT minzhao comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT junzhao comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT dawensui comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT yunwu comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT huichen comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT huiliu comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT jinxiazhang comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT erikaresetkova comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT stacylmoulder comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT weilienwang comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors AT leihuo comparisonofthreescoringmethodsusingthefdaapproved22c3immunohistochemistryassaytoevaluatepdl1expressioninbreastcancerandtheirassociationwithclinicopathologicfactors |