Assoziation der MICA/MICB-Allele mit der Progression kolorektaler Karzinome

Abstract

Introduction: The major histocompatibility complex class I related A (MICA) and MICB molecules are ligands of NKG2D receptors on gamma/delta natural killer cells and CD8aß T cells and mediate host antitumor immune response. The role of MICA and MICB alleles in patients with colorectal cancer has not yet been investigated. Methods: We have analyzed the MICA and MICB polymorphisms in patients with colorectal cancer (n = 81) by polymerase chain reaction (PCR) amplification, subsequent electrophoresis and sequencing in comparison to a previously analyzed cohort of healthy controls (n = 306). Allele frequencies obtained for MICA and MICB were compared with histopathological data (n = 68) regarding tumor invasion, disease progression, microsatellite instability and the presence of K-ras mutations (codon 12). Results: Allele frequencies of MICA and MICB polymorphisms were not different in patients with colorectal cancer in comparison to normal controls. Within the group of colorectal cancer patients the MICA A4 allele was directly (p = 0.012) correlated to the presence of distant metastasis, while the MICA A5 allele was associated with less lymph node involvement (p = 0.001) and earlier UICC stages (p = 0.01). Patients with genomic MICA A4 negative/A5 positive allele pattern had the lowest rate of tumor lymph node involvement or distant metastasis (p = 0.001). The MICB CA21 allele showed a trend for correlation with high microsatellite instability (p = 0.04). K-ras oncogene mutations were not associated with a specific pattern of MICA or MICB allele combinations. Conclusion: Specific MICA alleles seem to influence tumor progression of patients with colorectal cancer indicating an important role of host innate immune predisposition involving NKG2D mediated antitumor response.