Prognostic value of MACC1 and proficient mismatch repair status for recurrence risk prediction in stage II colon cancer patients: the BIOGRID studies


  • U.P. Rohr
  • P. Herrmann
  • K. Ilm
  • H. Zhang
  • S. Lohmann
  • A. Reiser
  • A. Muranyi
  • J. Smith
  • S. Burock
  • M. Osterland
  • K. Leith
  • S. Singh
  • P. Brunhoeber
  • R. Bowermaster
  • J. Tie
  • M. Christie
  • H.L. Wong
  • P. Waring
  • K. Shanmugam
  • P. Gibbs
  • U. Stein


  • Annals of Oncology


  • Ann Oncol 28 (8): 1869-1875


  • Background: We assessed the novel MACC1 gene to further stratify stage II colon cancer patients with proficient mismatch repair (pMMR). Patients and methods: Four cohorts with 596 patients were analyzed: Charite 1 discovery cohort was assayed for MACC1 mRNA expression and MMR in cryo-preserved tumors. Charite 2 comparison cohort was used to translate MACC1 qRT-PCR analyses to FFPE samples. In the BIOGRID 1 training cohort MACC1 mRNA levels were related to MACC1 protein levels from immunohistochemistry in FFPE sections; also analyzed for MMR. Chemotherapy-naive pMMR patients were stratified by MACC1 mRNA and protein expression to establish risk groups based on recurrence-free survival (RFS). Risk stratification from BIOGRID 1 was confirmed in the BIOGRID 2 validation cohort. Pooled BIOGRID datasets produced a best effect-size estimate. Results: In BIOGRID 1, using qRT-PCR and immunohistochemistry for MACC1 detection, pMMR/MACC1-low patients had a lower recurrence probability versus pMMR/MACC1-high patients (5-year RFS of 92% and 67% versus 100% and 68%, respectively). In BIOGRID 2, longer RFS was confirmed for pMMR/MACC1-low versus pMMR/MACC1-high patients (5-year RFS of 100% versus 90%, respectively). In the pooled dataset, 6.5% of patients were pMMR/MACC1-low with no disease recurrence, resulting in a 17% higher 5-year RFS (95% CI (12.6-21.3%)) versus pMMR/MACC1-high patients (P=0.037). Outcomes were similar for pMMR/MACC1-low and deficient MMR (dMMR) patients (5-year RFS of 100% and 96%, respectively). Conclusions: MACC1 E xpression stratifies colon cancer patients with unfavorable pMMR status. Stage II colon cancer patients with pMMR/MACC1-low tumors have a similar favorable prognosis to those with dMMR with potential implications for the role of adjuvant therapy.