Chao Li1, Cheng Huang2, Tony S Mok3, Wu Zhuang2, Haipeng Xu2, Qian Miao2, Xirong Fan2, Weifeng Zhu4, Yunjian Huang2, Xiandong Lin5, Kan Jiang2, Dan Hu4, Xiaohui Chen6, Peisha Huang7, Gen Lin8. 1. Department of Pathology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, People's Republic of China; Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, People's Republic of China. 2. Department of Thoracic Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, People's Republic of China. 3. The State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong. 4. Department of Pathology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, People's Republic of China. 5. Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, People's Republic of China; Department of Molecular Pathology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, People's Republic of China. 6. Department of Thoracic Surgery, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, People's Republic of China. 7. Fujian Medical University, Fujian, People's Republic of China. 8. Department of Thoracic Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, People's Republic of China. Electronic address: lingen197505@163.com.
Abstract
INTRODUCTION: The extent to which intratumoral heterogeneity of programmed death ligand 1 (PD-L1) expression causes discordance of PD-L1 expression between paired samples remains unclear. Here, PD-L1 status was compared between whole sections from NSCLCs and the corresponding tissue microarrays (TMAs) serving as surrogate biopsy specimens. METHODS: PD-L1 expression was evaluated by 22C3 immunohistochemistry assay on 190 archival surgical specimens and matched to the TMA results. PD-L1 expression was determined by the tumor proportion score (TPS) and classified as TPS lower than 1%, TPS of 1% to 49%, and TPS of 50% or higher. Agreement statistics were used. RESULTS: The percentage of PD-L1 expression on tumor cells differed greatly between individual TMAs and matched surgical specimens. When PD-L1 TPS was adopted, a total of 36 of 190 discordance cases (18.9%) were observed, with a κ-value of 0.630 between paired samples. The TMAs underestimated or overestimated PD-L1 status in 19 of 36 (52.8%) and 17 of 36 (47.2%) of the matched surgical specimens, respectively (p = 0.118). The discordance rate was much lower in cases with a PD-L1 TPS lower than 1% compared with in cases with a TPS of 1% to 49% and TPS of 50% or higher (18.4% versus 56.7% and 43.3%, p < 0.001). When a TPS of 50% or higher was used as the cutoff, the discordance rate of PD-L1 TPS less than 50% was further reduced to 7.5%. Such discrepancies were due mainly to intratumoral heterogeneity of PD-L1 expression and nonsignificant association with clinicopathological features. CONCLUSIONS: PD-L1 expression in TMAs correlates moderately well with that in the corresponding surgical specimens, indicating that evaluating PD-L1 expression in diagnostic biopsy specimens could be misleading in defining sensitivity to pembrolizumab treatment yet may be reliable as a way to exclude patients with a PD-L1 TPS less than 50% from first-line pembrolizumab treatment.
INTRODUCTION: The extent to which intratumoral heterogeneity of programmed death ligand 1 (PD-L1) expression causes discordance of PD-L1 expression between paired samples remains unclear. Here, PD-L1 status was compared between whole sections from NSCLCs and the corresponding tissue microarrays (TMAs) serving as surrogate biopsy specimens. METHODS:PD-L1 expression was evaluated by 22C3 immunohistochemistry assay on 190 archival surgical specimens and matched to the TMA results. PD-L1 expression was determined by the tumor proportion score (TPS) and classified as TPS lower than 1%, TPS of 1% to 49%, and TPS of 50% or higher. Agreement statistics were used. RESULTS: The percentage of PD-L1 expression on tumor cells differed greatly between individual TMAs and matched surgical specimens. When PD-L1 TPS was adopted, a total of 36 of 190 discordance cases (18.9%) were observed, with a κ-value of 0.630 between paired samples. The TMAs underestimated or overestimated PD-L1 status in 19 of 36 (52.8%) and 17 of 36 (47.2%) of the matched surgical specimens, respectively (p = 0.118). The discordance rate was much lower in cases with a PD-L1 TPS lower than 1% compared with in cases with a TPS of 1% to 49% and TPS of 50% or higher (18.4% versus 56.7% and 43.3%, p < 0.001). When a TPS of 50% or higher was used as the cutoff, the discordance rate of PD-L1 TPS less than 50% was further reduced to 7.5%. Such discrepancies were due mainly to intratumoral heterogeneity of PD-L1 expression and nonsignificant association with clinicopathological features. CONCLUSIONS:PD-L1 expression in TMAs correlates moderately well with that in the corresponding surgical specimens, indicating that evaluating PD-L1 expression in diagnostic biopsy specimens could be misleading in defining sensitivity to pembrolizumab treatment yet may be reliable as a way to exclude patients with a PD-L1 TPS less than 50% from first-line pembrolizumab treatment.
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