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Integrative analysis of PD ‐L1 DNA status, mRNA status and protein status, and their clinicopathological correlation, in diffuse large B‐cell lymphoma
Author(s) -
Sun Chenbo,
Jia Yijun,
Wang Weige,
Bi Rui,
Wu Lijing,
Bai Qianming,
Zhou Xiaoyan
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13765
Subject(s) - messenger rna , immunohistochemistry , diffuse large b cell lymphoma , cancer research , microbiology and biotechnology , pd l1 , biology , in situ hybridization , clinical significance , lymphoma , pathology , cancer , medicine , gene , immunology , genetics , immunotherapy
Aims The protein expression of programmed death‐ligand 1 ( PD ‐L1) has been recognised as being a biomarker for poor prognosis in diffuse large B‐cell lymphoma ( DLBCL ). The aims of this study were to determine PD ‐L1 DNA status and mRNA status, and to explore whether they contribute to protein expression and their clinicopathological correlation in DLBCL . Methods and results In this study, we used fluorescence in‐situ hybridisation, RNA in‐situ hybridisation and immunohistochemistry to determine PD ‐L1 status at three different levels in 287 DLBCL samples with follow‐up. Their correlation and clinical pathological relevance were also analysed. Our results showed that 1.7% (3/175) of patients had PD ‐L1 DNA amplification, 19.9% (57/287) had high PD ‐L1 mRNA expression, and 11.8% (34/287) had high PD ‐L1 protein expression. Both mRNA and protein expression of PD ‐L1 were significantly higher in non‐germinal centre B‐cell‐like ( GCB ) DLBCL than in GCB DLBCL ( P < 0.05). In addition, the patients with high PD ‐L1 mRNA or high PD ‐L1 protein expression but no PD ‐L1 DNA amplification had significantly poorer overall survival ( OS ) than those with low PD ‐L1 expression ( P < 0.05). Furthermore, we found that PD ‐L1 mRNA and PD ‐L1 protein expression were highly correlated ( P = 0.012), which was observed in all three samples with DNA amplification. Conclusions PD ‐L1 DNA amplification is a rare event, PD ‐L1 mRNA is the main contributor to the high PD ‐L1 protein expression, and the latter two will serve as important biomarkers for predicting the prognosis of DLBCL patients and selecting them for immunotherapy.