Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein-Barr virus status, and cancer genome alterations in metastatic gastric cancer.

Abstract

BACKGROUND:

Recently, the U.S. Food and Drug Administration approved pembrolizumab for patients (pts) with PD-L1-positive metastatic gastric cancer (MGC) based on 22C3 immunohistochemistry (IHC) assay. However, little is known about detailed clinicopathological features of 22C3 PD-L1 expression in MGC.

PATIENTS AND METHODS:

Pts with histologically confirmed MGC were eligible for this prospective observational study. PD-L1 expression (22C3) on tumor cell (TC) or immune cell (IC) and mismatch repair (MMR) were analyzed by IHC. Epstein-Barr virus (EBV) was detected by in situ hybridization. The expressions of tyrosine kinase receptors (RTKs) and cancer genome alterations were evaluated by IHC or next-generation sequencing.

RESULTS:

A total of 225 pts were analyzed in this study. PD-L1 expression on TC, PD-L1 on IC, MMR-deficient (D-MMR), and EBV positivity were identified in 8.4, 65.3, 6.2, and 6.2% cases, respectively. PD-L1 expression in TC was more frequently observed in pts with D-MMR (P < 0.001), PIK3CA mutation (P = 0.020), and KRAS mutation (P = 0.002), and PD-L1 on IC was associated with EBV positivity (P = 0.034), and lymph-node metastasis (P < 0.001). PD-L1 expression on either IC or TC was less frequently observed in pts with peritoneal metastasis and Borrmann Type 4. A significant association was not observed between PD-L1 expression and RTKs expression or presence of other gene alterations. PD-L1 expression on either TC or IC was not prognostic factor.

CONCLUSIONS:

22C3 PD-L1 expression in MGC was associated with distinct clinicopathological features, but was not a prognostic factor.

• Authors: Akihito Kawazoe, Kohei Shitara, Yasutoshi Kuboki, Hideaki Bando, Takashi Kojima, Takayuki Yoshino, Atsushi Ohtsu, Atsushi Ochiai, Yosuke Togashi, Hiroyoshi Nishikawa, Toshihiko Doi, Takeshi Kuwata
• Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (Gastric Cancer) Vol. 22 Issue 1 Pg. 69-76 (01 2019) ISSN: 1436-3305 [Electronic] Japan
• PMID: 29859006 (Publication Type: Journal Article, Observational Study)

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• B7-H1 Antigen (biosynthesis)
• Biomarkers, Tumor (analysis)
• DNA Mismatch Repair
• Epstein-Barr Virus Infections (complications)
• Female
• Herpesvirus 4, Human
• Humans
• Male
• Middle Aged
• Prospective Studies
• Stomach Neoplasms (genetics, pathology, virology)
• Young Adult