Significance of PD‑L1 clones and C‑MET expression in hepatocellular carcinoma
Affiliations: Sunchun Sarang Hospital, Suncheon‑si, Jeollanam‑do 57993, Republic of Korea, Department of Pathology, College of Medicine, Chosun University, Donggu, Gwangju 61453, Republic of Korea
- Published online on: April 5, 2019 https://doi.org/10.3892/ol.2019.10222
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Programmed cell death ligand 1 (PD‑L1) is an essential immune checkpoint protein implicated in immune evasion by malignant tumors. Overexpression of programmed cell death protein 1 (PD‑1) and its ligand PD‑L1 is associated with poor prognosis in various types of cancer. Recently, multiple advances have occurred in the area of cancer immunotherapy. Inhibiting the ligation of PD‑1 by PD‑L1 has been the major focus of anti‑tumor immunotherapy. In diagnostic pathology, it has become crucial to detect PD‑L1+ tumor cases using a validated immunohistochemistry (IHC) approach. Preliminary data demonstrate that C‑MET promotes survival of some (e.g., renal) cancer types through regulation of PD‑L1. However, C‑MET expression, and its association with PD‑L1, has not been well‑characterized in the context of hepatocellular carcinoma (HCC), and no anti‑HCC immunotherapy is currently available in Korea. Therefore, it is crucial to investigate the expression of C‑MET and PD‑L1, and their association with clinicopathologic factors, to facilitate the development of targeted treatments for HCC. PD‑L1 expression was examined in tumor cells (TC) and immune cells (IC) of 70 patient‑derived HCC specimens using IHC. Two anti‑PD‑L1 monoclonal antibodies (MAbs), SP263 and SP142, were utilized. Additionally, TC C‑MET expression was assessed. Correlations between PD‑L1 expression (as identified by both MAbs), C‑MET expression and clinicopathologic factors were assessed. More PD‑L1+ cases were identified via SP263 than via SP142 when assessing both TC and IC; in the former group, SP236 identified 14/70 positive cases, while SP142 identified only 2/70. In the latter group, SP236 identified 49/70 positive cases, while SP142 identified 30/70. Both MAbs demonstrated a higher frequency of PD‑L1 expression by IC than TC. The Edmondson‑Steiner grade statistically correlated with a higher frequency of SP236‑detected TC PD‑L1 expression. C‑MET was significantly associated with advanced tumor size and was positively correlated with SP263‑detected PD‑L1 expression in TC. These results suggest that C‑MET may serve a role in regulating PD‑L1 expression in HCC. Furthermore, while SP263 generally exhibited a higher sensitivity for PD‑L1 detection, concordance in PD‑L1+ case detection between the two different MAbs was generally good. These background data may be helpful in the development of targeted anti‑HCC immunotherapy focused on PD‑L1 or C‑MET, and in evaluating selection criteria for target populations best suited to such treatments.