Role of PD-L1 Expression during the Progression of Submucosal Gastric Cancer

<b><i>Introduction:</i></b> Programmed death-ligand 1 (PD-L1) expression is a prognostic marker for gastric cancer that correlates with tumor diameter and depth of penetration. But the role of PD-L1 and mechanism(s) employed in the initial phase of invasion in early gastric cancer is yet to be understood. <b><i>Objective:</i></b> This study aims to elucidate the role of PD-L1 during the progression of gastric cancer, specifically invading the submucosa beyond the lamina muscularis mucosa. <b><i>Methods:</i></b> Using 107 patients with pathological submucosal gastric cancer, we determined the expression of PD-L1 based on the staining of the cell membrane or cytoplasm of tumor cells in the central and invasive front of the tumor. Samples were categorized into 3 groups based on the intensity of PD-L1 expression. CD8⁺ lymphocytes expressing PD-1 and CD163⁺ macrophages were used to determine the number of cell nuclei at the invasive front, similar to PD-L1. CMTM6 levels were determined and used to stratify samples into 3 groups. <b><i>Results:</i></b> PD-L1 expression was higher in the invasive front (26.2%) than in the central portion of the tumors (7.4%; <i>p</i> &#x3c; 0.001). Moreover, lymphatic and vascular invasion were more frequently observed in samples with high levels of PD-L1 (lymphatic invasion: 60.7 vs. 35.4%, <i>p</i> = 0.0026, and vascular invasion: 39.3 vs. 16.5%, <i>p</i> = 0.0018). There was no correlation between PD-L1 expression and the levels of PD-1, CD8, CD163, and CMTM6. <b><i>Conclusions:</i></b> PD-L1-expressing cancer cells at the invasive front of gastric cancer influence the initial stages of tumor invasion and lymphovascular permeation in early-stage gastric cancers. Immune checkpoint signaling may be the driving force in the invasive front during the invasion of the submucosa beyond the lamina muscularis mucosa.

The ratio of major and minor axis by EUS as a possible predictive marker for the diagnosis of submucosal invasive gastric cancer.

9 Background: The aim of this study was to evaluate the efficacy of the ratio of major and minor axis by endoscopic ultrasonography (EUS) as a possible predictive marker for the diagnosis of submucosal invasive gastric cancer. Methods: Between March 2014 and December 2014, the medical records of 51 patients with unclear distinction between mucosal and submucosal gastric cancer were retrospectively reviewed. Patient and tumor characteristics, accuracy rate and factors associated with correct diagnosis of submucosal invasive tumor in Ratio for gastric cancer were analyzed. Results: The mean age was 62.0 ± 12.6 (range, 35-79 years) and the male to female ratio was 1:0.45. The mean tumor size was 25.8 ± 14.7 mm. The overall accuracy was 60.7% (31/51) using the EUS and 82.3% (42/51) using the EUS ratio index (p = 0.045). The sensitivity, specificity, positive predictive value and negative predictive value to submucosal gastric cancer were 68.1, 55.1, 53.5, 65.9% using the EUS and 81.8,82.7,78.2,85.7% using the EUS ratio index, respectively. In the multivariate analysis, differentiated (Odds ratio [OR]: 1.42, 95% confidence interval [CI]: 0.95-1.89), no ulceration (OR: 1.96, 95% CI: 1.49-2.43), and deep submucosal invasion ( > 500 μm, OR: 2.77, 95% CI: 2.16-3.34) were independent factors, associated with correct diagnosis of submucosal invasive tumor in Ratio for gastric cancer (p < 0.05) Conclusions: The ratio of major and minor axis by endoscopic ultrasonography (EUS ratio index) might be a possible predictive marker for the diagnosis of submucosal invasive gastric cancer.