Expression level and prognostic value of PD-L1 in microsatellite instability-high gastric cancer

Abstract

Objective: To study the clinicopathological features and PD-L1 expression of microsatellite instability-high (MSI-H) gastric cancer. Methods: The clinicopathological data of the 2 472 patients who had undergone radical surgical resection and been performed immunohistochemical staining of four major mismatch repair (MMR) proteins (MLH1, PMS2, MSH2 and MSH6) from March 2014 to December 2018 at Peking University Cancer Hospital were collected. One hundred and seventy-one patients showed mismatch repair-deficient (dMMR), and microsatellite instability of these patients were detected with polymerase chain reaction (PCR). Then, taken PCR results as the standard, PD-L1 was assessed using immunohistochemistry (IHC) in the MSI-H gastric cancers. Results: MSI-H (vs. MSI-L) in gastric cancers was associated with female gender, advanced age, gastric-antrum location, intestinal type, lesion diameter exceeding 5 cm, absence of lymph node metastasis and positive PD-L1 expression (P<0.05, respectively). Combined positive score (CPS) was an independent risk factor (P=0.026, HR=8.385, 95%CI=1.293-54.367). Although no relationship between PD-L1 expression pattern and prognosis was observed,"diffuse-pattern" of the PD-L1 expression was related to lymphatic-vascular invasion (P=0.007) and infiltration depth (P=0.04). Among the patients with MSI-H and PD-L1 positive gastric cancer, the patients who experienced recurrence or died all had the pattern of "diffuse" PD-L1 expression. Also, regarding the expression level and staining pattern of PD-L1, the metastasis lesion of lymph node had a high coincidence with primary site (P=0.45). Conclusions: MSI-H gastric cancer shows distinctive clinicopathological characteristics. The CPS can be used as a prognostic indicator in MSI-H gastric cancers, while the "diffuse-pattern" of PD-L1 expression could possibly be used as a prognostic indicator. The patients with advanced gastric cancer could obtain the expression level and staining pattern of PD-L1 using the biopsy material of metastatic lesions.