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. 2009 Jul;29(4):545-54.
doi: 10.1007/s10875-009-9288-6. Epub 2009 Apr 8.

Association of MICA-TM and MICB C1_2_A microsatellite polymorphisms with tumor progression in patients with colorectal cancer

R Kopp  1 , J Glas, U Lau-Werner, E D Albert, E H Weiss
Affiliations

Association of MICA-TM and MICB C1_2_A microsatellite polymorphisms with tumor progression in patients with colorectal cancer

R Kopp et al. J Clin Immunol. 2009 Jul.

Abstract

Purpose: The major histocompatibility complex class I related A (MICA) and MICB molecules are ligands of NKG2D receptors on natural killer cells, gamma/delta T cells, and CD8ass T cells that mediate host antitumor immune response. The role of MICA-TM and MICB C1_2_A alleles in patients with colorectal cancer has not yet been investigated.

Methods: We have analyzed the MICA-TM and MICB C1_2_A polymorphisms in colorectal cancer patients (n = 79) by polymerase chain reaction amplification, subsequent electrophoresis, and sequencing in comparison to a previously analyzed cohort of healthy controls (n = 306). Allele frequencies obtained for MICA-TM and MICB C1_2_A were compared to histopathological data regarding tumor invasion, disease progression, microsatellite instability, and the presence of KRAS mutations (codon 12) and analyzed for possible impact on tumor-related survival (n = 61).

Results: Allele frequencies of MICA-TM and MICB C1_2_A polymorphisms were not different in patients with colorectal cancer in comparison to normal controls. In colorectal cancer patients, MICA-TM A4 allele was directly and MICA-TM A5 allele was inversely associated with lymph node involvement and advanced UICC stages. Tumor-related survival in colorectal cancer patients was significantly reduced in the presence of the MICA-TM A4 allele (p = 0.015). In patients with microsatellite stable tumors, survival was reduced in association with the MICA-TM A4 allele (p = 0.006) and MICA-TM A9 allele (p = 0.034), but increased in patients showing the MICA-TM A5 allele (p = 0.042).

Conclusions: Specific MICA-TM alleles seem to influence tumor progression and midterm survival of patients with colorectal cancer, indicating an important role of host innate immune predisposition involving NKG2D mediated antitumor response.

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Figures

Fig. 1
Fig. 1
Survival analysis in relation to MICA-TM A4 allele haplotype. Kaplan–Meier analysis of tumor-related survival times in association with MICA-TM A4 allele in patients with colorectal cancer. Short vertical lines indicate censored observations for comparison of patients without (n = 46) and with MICA-TM A4 allele (n = 15, p = 0.015)
Fig. 2
Fig. 2
MICA-TM A4 allele detection in microsatellite stable colorectal cancer patients. Kaplan–Meier analysis of tumor-related survival times in association with MICA-TM A4 allele in patients with microsatellite stable colorectal cancer. Vertical lines indicate censored observations for comparison of patients without (n = 42) and with MICA-TM A4 allele (n = 12, p = 0.006). The estimated 5-year survival rate was 72% vs 38%, respectively
Fig. 3
Fig. 3
MICA-TM A4 or A9 haplotype in microsatellite stable colorectal cancer patients. Kaplan–Meier analysis of tumor-related survival times in association with MICA-TM A4 or A9 alleles in patients with microsatellite stable colorectal cancer. Vertical lines indicate censored observations for comparison of patients either positive for MICA-TM A4 or A9 alleles (n = 23) in comparison to patients without MICA-TM A4 and A9 alleles (n = 31, p ≤ 0.001)
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