Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

Tanaka,Kimitaka; Tsuchikawa,Takahiro; Miyamoto,Masaki; Maki,Takehiro; Ichinokawa,Masaomi; Kubota,Kanako  C.; Shichinohe,Toshiaki; Hirano,Satoshi; Ferrone,Soldano; Dosaka-Akita,Hirotoshi; Matsuno,Yoshihiro; Kondo,Satoshi

doi:10.3892/ijo.2011.1274

Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

Authors:
- Kimitaka Tanaka
- Takahiro Tsuchikawa
- Masaki Miyamoto
- Takehiro Maki
- Masaomi Ichinokawa
- Kanako C. Kubota
- Toshiaki Shichinohe
- Satoshi Hirano
- Soldano Ferrone
- Hirotoshi Dosaka-Akita
- Yoshihiro Matsuno
- Satoshi Kondo
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Affiliations: Department of Surgical Oncology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8648, Japan
Published online on: November 30, 2011 https://doi.org/10.3892/ijo.2011.1274
Pages: 965-974

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Abstract

The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP‑1, TAP-2, LMP-7 and LMP-10. Immunohistochemical staining utilizing a tissue microarray method for HLA class I APM expression showing different expression patterns among cell lines was performed for 95 surgical specimens from patients with esophageal cancer. Prognostic factors were the down-regulation of HLA-HC, and the up-regulation of β2 microglobulin and TAP-1 in the cancer tissues. Multivariate analysis using a Cox regression model indicated that the down-regulation of HLA-HC, and up-regulation of TAP-1 in cancer tissues are independent, unfavorable prognostic factors (hazard ratio, 2.361 and 2.297; P=0.0141 and 0.0145, respectively). Although there was no significant difference in survival for selected p-stage I and II patients (n=54) in all APM components, only down-regulation of HLA-HC was an unfavorable prognostic factor by a Cox regression model for selected p-stage III and IV patients (n=41). In conclusion, the current results suggest that the down-regulation of HLA-HC in tumors is especially associated with a poor prognosis among advanced esophageal cancer patients.

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