Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients

Ribeiro,Carolina  Hager; Kramm,Karina; Gálvez-Jirón,Felipe; Pola,Víctor; Bustamante,Marco; Contreras,Hector  R.; Sabag,Andrea; Garrido-Tapia,Macarena; Hernández,Carolina  J.; Zúñiga,Roberto; Collazo,Norberto; Sotelo,Pablo  Hernán; Morales,Camila; Mercado,Luis; Catalán,Diego; Aguillón,Juan  Carlos; Molina,María  Carmen

doi:10.3892/or.2015.4510

Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients

Authors:
- Carolina Hager Ribeiro
- Karina Kramm
- Felipe Gálvez-Jirón
- Víctor Pola
- Marco Bustamante
- Hector R. Contreras
- Andrea Sabag
- Macarena Garrido-Tapia
- Carolina J. Hernández
- Roberto Zúñiga
- Norberto Collazo
- Pablo Hernán Sotelo
- Camila Morales
- Luis Mercado
- Diego Catalán
- Juan Carlos Aguillón
- María Carmen Molina
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Affiliations: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile, Departamento de Cirugía Digestiva, Hospital del Salvador, Universidad de Chile, Santiago, Chile, Programa de Fisiología y Biofísica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile, Facultad de Química, Universidad de la República, Montevideo, Uruguay, Centro de InmunoBiotecnología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile, Instituto de Biología, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
Published online on: December 23, 2015 https://doi.org/10.3892/or.2015.4510
Pages: 1309-1317
Copyright: © Ribeiro et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer (GC) is the third most common cause of cancer death worldwide. Natural killer cells play an important role in the immune defense against transformed cells. They express the activating receptor NKG2D, whose ligands belong to the MIC and ULBP/RAET family. Although it is well established that these ligands are generally expressed in tumors, the association between their expression in the tumor and gastric mucosa and clinical parameters and prognosis of GC remains to be addressed. In the present study, MICA and MICB expression was analyzed, by flow cytometry, in 23 and 20 pairs of gastric tumor and adjacent non-neoplasic gastric mucosa, respectively. Additionally, ligands expression in 13 tumors and 7 gastric mucosa samples from GC patients were evaluated by immunohistochemistry. The mRNA levels of MICA in 9 pairs of tumor and mucosa were determined by quantitative PCR. Data were associated with the clinicopathological characteristics and the patient outcome. MICA expression was observed in 57% of tumors (13/23) and 44% of mucosal samples (10/23), while MICB was detected in 50% of tumors (10/20) and 45% of mucosal tissues (9/20). At the protein level, ligand expression was significantly higher in the tumor than in the gastric mucosa. MICA mRNA levels were also increased in the tumor as compared to the mucosa. However, clinicopathological analysis indicated that, in patients with tumors >5 cm, the expression of MICA and MICB in the tumor did not differ from that of the mucosa, and tumors >5 cm showed significantly higher MICA and MICB expression than tumors ≤5 cm. Patients presenting tumors >5 cm that expressed MICA and MICB had substantially shorter survival than those with large tumors that did not express these ligands. Our results suggest that locally sustained expression of MICA and MICB in the tumor may contribute to the malignant progression of GC and that expression of these ligands predicts an unfavorable prognosis in GC patients presenting large tumors.

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