Lack of MICA Expression Predicts a Worse Prognosis in Patients with Bladder Cancer

Mauricio Orozco-Levi, Alba Ramírez-Sarmiento, Michael Borchers, Cristiane Murta-Nascimento, Francesc Macià, Beatriz Casado, Maeba Polo, Andrea Caballero-Benitez, Fredy Diaz-Quijano, Antoni Gelabert

American Organization for the Promotion of Health Research (OLFIS), Bucaramanga, Colombia.
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CibeRes), Instituto de Salud Carlos III, Ministerio de Ciencia y Tecnología, Spain.
Consorcio de Investigación Biomédica de Epidemiología y Salud Pública (CIBERESP), Spain.
Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, USA.
Epidemiology and Health Services Evaluation Department, Hospital del Mar-Parc de Salut Mar, Barcelona, Spain.
Group of Research in Injury, Immune Response and Lung Function (LIF), Hospital del Mar Research Institute (IMIM).
Urology Department, Group of Research in Solid Tumors, Universidad Autónoma de Barcelona, Barcelona, Spain.

DOI: 10.4236/ojpathology.2013.31008                

Abstract

Background: Bladder and lung cancer are among the ten most common cancers in both genders. The NKG2D receptor and one of its ligands, MICA, are associated with smoking and susceptibility to both chronic obstructive pulmonary disease and lung cancer. Objective: We hypothesized that NKG2D-MICA system was associated with other smoking-related epithelial cancers such as bladder cancer. Design, Setting, and Participants: 70 cases of primary non-muscle invasive bladder cancer were screened for the MICA expression and CD8+, CD4+ and NK cell infiltration. Most patients (n = 55, 78.6%) were current or former smokers. Measurements: Tissue microarray (TMA) technology was chosen to evaluate MICA and tumor infiltrating lymphocytes in samples with confirmed bladder cancer. Kaplan-Meier curves and univariate Cox analysis was used to assess relapse, all-cancer mortality and specific bladder cancer mortality. Results and Limitations: MICA was expressed in most cancer specimens examined (i.e., 70%). Relapse of bladder cancer was not associated with the status of MICA expression (log rank p = 0.1123). Nevertheless, a significant association existed between high MICA expression and bladder cancer mortality (HR = 0.25; CI_95% = 0.06 - 0.97). Tumor infiltrating CD4+ and CD8+ lymphocytes were found in the majority (64%) of samples. Cells expressing the NKG2D receptor were found in only 3% of the samples. There was no linear function between NKG2D+ cells and number or ratio of CD4+ and CD8+ TIL. Conclusions: MICA is expressed in a significant proportion of bladder carcinomas. MICA expression associates with significant survival advantages in the face of both all-cancer and bladder cancer. The NKG2D-MICA system could represent a common mechanism involved in the immunopathology and natural history of bladder neoplasms.

Keywords

Bladder Cancer; NKG2D Ligands; MICA; Survival; Prognosis

Conflicts of Interest

The authors declare no conflicts of interest.

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