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

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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number69
JournalBreast Cancer Research
Volume22
Issue number1
DOIs
StatePublished - Jun 23 2020

Keywords

  • 22C3
  • Breast cancer
  • Immunohistochemistry
  • PD-L1
  • Race/ethnicity
  • Scoring methods
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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