Cancer Letters

Cancer Letters

Volume 168, Issue 1, 10 July 2001, Pages 87-91
Cancer Letters

Invariant chain expression in gastric cancer

https://doi.org/10.1016/S0304-3835(01)00503-1Get rights and content

Abstract

Invariant chain (Ii) is a chaperone molecule that inhibits the binding of endogenous antigens to HLA class II. The tumor cell with overexpressed Ii chain is thought to escape attacking cytotoxic lymphocytes by suppressing the host immune. However, the relationship between Ii expression by the tumor and clinicopathological factors in gastric cancer remains unclear. We studied 126 patients with gastric cancer who had undergone curative gastrectomy at Kagoshima University Hospital between 1988 and 1997. In order to detect Ii and HLA-DR expression by tumor cells, immunohistochemical staining with anti-CD74 and anti-HLA-DR antibodies were performed by avidin-biotin peroxidase complex method. The 126 patients studied were divided into two groups based on Ii expression. Ii and HLA-DR were expressed both on the surface and in the cytoplasm of tumor cells and tumor infiltrating lymphocytes. A total of 48 patients were identified as Ii positive, while the remaining 78 patients were Ii negative. Ii expression negatively correlated with the depth of invasion of the tumor as well as the patients’ clinical stage. Ii expression was negatively correlated with HLA-DR expression. Patients with Ii negative expression had significantly better surgical outcomes than those with Ii positive expression (P<0.05). Ii expression in gastric cancer affected surgical outcome and Ii expression was negatively correlated with depth of invasion and HLA-DR expression. Ii expression in gastric cancer may be a prognostic factor related to suppressive effects on host immune responses to tumor cells.

Introduction

Intracytoplasmic invariant chain (Ii) protein is a chaperone molecule which regulates the function of HLA class II molecules [1], [2]. Ii protein regulates antigen presentation by HLA class II molecules by inhibiting their cytoplasmic form from binding to endogenously derived antigenic peptides. Recent work on the mechanisms involved in anti-tumor immune response has indicated that humoral mediators or abnormal expression of tumor-associated antigens result in low lymphocytic response against tumor cells [3], [4], [5]. It has been elucidated that Ii in cancer cells was one of the molecules related with immunosuppression [6]. Increased Ii expression in tumor cells inhibits tumor antigen presentation by HLA class II molecules, disrupting the HLA class II mediated immune stimulation by tumor cells [7]. Thus, Ii positive tumor cells may have a significant influence on tumor behavior.

Previous studies on HLA-DR expression in several cancers including gastric cancers revealed a positive relationship between Human Leukocyte Antigen-DR (HLA-DR) expression and prognosis of the disease [8], [9], [10]. However, clinicopathological characteristics correlated with Ii expression and its prognostic implication were not fully disclosed. We herein attempt to clarify, retrospectively, the clinicopathological features of Ii positive gastric cancer.

Section snippets

Materials and methods

One hundred and twenty six patients who had undergone gastrectomy for gastric cancer between 1988 and 1995 at the First Department of Surgery, Kagoshima University School of Medicine were entered into this study. The mean age of the participants was 65.0 years (range 30–87), and the male /female ratio was 2.6 (91/35). One hundred and twelve patients received curative resection, while the remaining 14 underwent non-curative gastrectomy. A total of 60 patients received total gastrectomy, 51

Results

Both HLA-DR (Fig. 1) and Ii (Fig. 2) immunoreactivity was identified on the surface of the tumor cells. Some populations of tumor infiltrating lymphocytes were also immunopositive for those markers. Patients were divided into groups according to Ii or HLA-DR expression: 48 patients were placed in the Ii positive group, and 78 patients were placed in the Ii negative group. The HLA-DR positive group consisted of 46 patients while 80 patients were placed in the HLA-DR negative group.

Discussion

It has been suggested that increased Ii expression in tumor cells prevents presentation of tumor antigens by HLA class II molecules [6]. Poor antigen presentation to intratumoral T-cells may then weaken the host immune defense against tumor cells. There are few clinical studies on Ii expression in cancer patients [6], [12] and the results are not always similar, indicating the need for further investigation. This study describes Ii expression in gastric cancer and, for the first time, shows a

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