Virchows Archiv

, Volume 459, Issue 1, pp 55–63

Differential clinicopathological features in microsatellite instability-positive colorectal cancers depending on CIMP status

Authors

  • Jeong Mo Bae
    • Department of PathologySeoul National University College of Medicine
  • Mi Jung Kim
    • Department of Diagnostic PathologyAsan Medical Center
  • Jung Ho Kim
    • Department of PathologySeoul National University College of Medicine
  • Jae Moon Koh
    • Department of PathologySeoul National University College of Medicine
  • Nam-Yun Cho
    • Laboratory of Epigenetics, Cancer Research Institute and 2nd Stage Brain KoreaSeoul National University College of Medicine
  • Tae-You Kim
    • Department of Internal MedicineSeoul National University College of Medicine
    • Department of PathologySeoul National University College of Medicine
    • Laboratory of Epigenetics, Cancer Research Institute and 2nd Stage Brain KoreaSeoul National University College of Medicine
Original Article

DOI: 10.1007/s00428-011-1080-3

Cite this article as:
Bae, J.M., Kim, M.J., Kim, J.H. et al. Virchows Arch (2011) 459: 55. doi:10.1007/s00428-011-1080-3

Abstract

Microsatellite instability-positive (MSI+) colorectal cancers (CRCs) are divided into CpG island methylator phenotype-positive (CIMP+) and CpG island methylator phenotype-negative (CIMP−) tumors. The repertoire of inactivated genes in CIMP+/MSI+ CRCs overlaps with but is likely to differ from that of CIMP−/MSI+ CRCs. Because epigenotypic differences are likely to be manifested as phenotypic differences, CIMP+/MSI+ CRCs are expected to differ from CIMP−/MSI+ CRCs in some clinicopathological features. This study aimed to characterize both common and different features between the two subtypes. A total of 72 MSI+ CRCs were analyzed for their methylation status in eight CIMP panel markers using MethyLight assay. CIMP+/MSI+ and CIMP−/MSI+ CRCs were compared regarding clinicopathologic features and mutation in KRAS/BRAF. An independent set of MSI+ CRCs (n = 97) was analyzed for their relationship of CIMP+ status with clinical outcome. Eighteen cases (25%) were CIMP+, and this CIMP+ subtype was highly correlated with older age (P < 0.001). Polypoid gross appearance without ulceration was observed only in CIMP−/MSI+ CRCs (18.5%, P = 0.057). CIMP+/MSI+ CRCs were closely associated with poor differentiation, medullary appearance, signet ring cell appearance, and acinar-form appearance, whereas the CIMP−/MSI+ subtype was closely associated with intraglandular eosinophilic mucin and stratified nuclei (all P values <0.05). Patients with CIMP+/MSI+ CRCs showed worse overall survival than patients with CIMP−/MSI+ CRCs. Our results demonstrate heterogeneity in the clinicopathological features of MSI+ CRCs depending on CIMP status. The observation that CIMP+ and CIMP− subtypes showed different clinical behaviors may provide a clue for establishing subtype-specific therapeutic strategies for these two subtypes.

Keywords

Colon cancerCpG islandDNA methylationMicrosatellite instabilityPrognosis

Copyright information

© Springer-Verlag 2011