Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance
Introduction
Gastric carcinoma is one of the most common causes of death from cancer in China. The postoperative survival of patients with advanced gastric carcinoma remains very poor, despite the standardization of surgical operations and multimodal therapies (Chen et al., 2000; Pisani et al., 1999; Roder, 2002). Thus, to improve prognosis of patients, novel strategies need to be developed and established. It is well known that development and prognosis of malignant tumors are closely related to host immune functions. The induction of anti-tumor immune responses needs the host immune system to identify the tumor antigen efficiently and to activate various T cells. Co-stimulatory molecules and regulative networks play an important role in this progression. Co-stimulatory molecules can be divided into two groups: the tumor necrosis factor (TNF)-TNF receptor (TNFr) superfamily and the immunoglobulin (Ig) superfamily (Chambers and Allison, 1999). Programmed death-1 (PD-1) is a co-stimulatory molecule that provides an inhibitory signal in T-cell activation (Pardoll, 2002). Two binding ligands (PD-L1, also named B7-H1, and PD-L2) for PD-1 have been identified, and both belong to the B7 family (Dong et al., 1999; Tseng et al., 2001). Recent studies have indicated that PD-L1 is expressed in dendritic cells (DCs) and in various tumor cells (Ohigashi et al., 2005; Yamazaki et al., 2002; Yuan et al., 2004) and may play an important role in inducing the special apoptosis of T cells and tumor immune escape. PD-L1 has been reported in human carcinoma of lung, ovary, colon and esophagus (Dong et al., 2002; Ohigashi et al., 2005). However, the presence of PD-L1 and its clinical significance in gastric cancer has not been investigated. In the present immunohistochemical study, we investigated PD-L1 in gastric carcinoma, adenoma and normal tissues, and further investigated the correlation between PD-L1 immunoreactivity and the prognosis of gastric carcinoma.
Section snippets
Materials
In total, 102 tissue samples were collected from patients (75 men and 27 women, aged from 28 to 77 years old, mean age 55 years old) who had gastric carcinoma and underwent surgical treatment in the hospital. A summary of the clinical features of the cases is listed in Table 1. No patient received chemotherapy or radiotherapy before surgery. Ten gastric adenoma samples from patients who underwent surgery (7 men and 3 women, 55–67 years old; mean age 60 years old), and 10 normal gastric samples
PD-L1 immunolabeling in gastric carcinoma, adenoma and normal tissues
There was no PD-L1 immunolabeling in normal gastric tissues and only very weak labeling in the gastric adenoma tissues; however, about 42.2% of gastric carcinoma tissues showed positive PD-L1 immunolabeling (Table 1). An example of typical, positive labeling of PD-L1 is shown in Fig. 1. There was no correlation between PD-L1 and age, sex, tumor location or tumor differentiation of patients; however, PD-L1 was significantly correlated to lymph node metastasis (χ2=9.730, ), tumor size (χ2
Discussion
The present study demonstrated that there were significant correlations between PD-L1 immunolabeling and tumor size, depth of invasion, lymph node metastasis and survival time of patients with gastric carcinomas. PD-L1 immunolabeling was significantly increased (), especially when the tumor infiltrated into the deep muscular layers, with lymph node metastasis and survival time less than 2 years, whereas there was no PD-L1 immunoreactivity detected in the normal gastric tissues and very
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