MIC-1 serum level and genotype: Associations with progress and prognosis of colorectal carcinoma

David A. Brown, Robyn L. Ward, Philip Buckhaults, Tao Liu, Katharine E. Romans, Nicholas J. Hawkins, Asne R. Bauskin, Kenneth W. Kinzler, Bert Vogelstein, Samuel N. Breit

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the tumor growth factor β (TGF-β) superfamily. Several observations suggest that it plays a role in colorectal carcinoma (CRC). In particular, MIC-1 is markedly up-regulated in colorectal cancers as well as in premalignant adenomas. This study examines the relationship of serum MIC-1 levels and genotypes to clinical and pathologic features of colonic neoplasia. Experimental Design: We confirmed the presence of MIC-1 in CRC tissue and the cell line CaCo-2. The normal range for serum MIC-1 levels was defined in 260 healthy blood donors, and the differences between normal subjects and 193 patients having adenomatous polyps or CRC were then determined. In a separate cohort of 224 patients, we evaluated the relationship of MIC-1 serum level and genotype to standard tumor parameters and outcome measures. Results: MIC-1 was expressed in CRC tissue and the cancer cell line CaCo-2. There was a progressive increase in serum MIC-1 levels between normal individuals [mean (M) = 495 pg/ml, SD = 210), those with adenomatous polyps (M = 681 pg/ml, SD = 410), and those with CRC (M = 783 pg/ml, SD = 491)]. Serum MIC-1 level was correlated with the extent of disease so that the levels were higher in patients with higher Tumor-Node-Metastasis stage. There were significant differences in time to relapse and overall survival between subjects with different MIC-1 levels and genotypes. Conclusions: This study identifies a strong association between MIC-1 serum levels and neoplastic progression within the large bowel. We suggest that the measurement of serum MIC-1 levels and determination of MIC-1 genotype may have clinical use in the management of patients with CRC.

Original languageEnglish (US)
Pages (from-to)2642-2650
Number of pages9
JournalClinical Cancer Research
Volume9
Issue number7
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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