International Journal of Colorectal Disease

, Volume 23, Issue 4, pp 365–373 | Cite as

Clinicopathologic and molecular features of sporadic microsatellite- and chromosomal-stable colorectal cancers

  • Guoxiang Cai
  • Ye Xu
  • Hongfen Lu
  • Yingqiang Shi
  • Peng Lian
  • Junjie Peng
  • Xiang Du
  • Xiaoyan Zhou
  • Zuqing Guan
  • Daren Shi
  • Sanjun Cai
Original Article

Abstract

Background and aims

Chromosomal instability (CIN) and microsatellite instability (MSI) are two major causes of colorectal cancers. Recently, a percentage of colorectal cancers were found to be neither CIN nor MSI. This study was performed to explore whether microsatellite- and chromosomal-stable (MACS) colorectal cancers comprise a substantially distinct subtype.

Materials and methods

Sixty-nine sporadic colorectal cancers were classified into three subsets according to ploidy and microsatellite instability status: CIN+, MSI+, and MACS. Clinicopathologic, genetic, and epigenetic differences among these three groups were investigated by immunohistochemical analysis of p53, APC, hMLH1, and BAX and methylation study of p14 ARF , hMLH1, p16 INK4a , MGMT, and MINT1 with methylation-specific polymerase chain reaction.

Results

The 69 cases included 49 CIN+, 7 MSI+, and 13 MACS. MACS were found to differ from CIN+ and MSI+ in three aspects. The clinicopathologic features of MACS were similar to MSI+ but distinguished from CIN+. Comparatively, MACS preferred proximal location and poor differentiation (p < 0.05). An immunohistochemical study demonstrated that MACS had a lower rate of loss of hMLH1 or BAX protein than MSI+ and less loss of APC protein than CIN+. In an epigenetic aspect, both MACS and MSI+ had a high rate of CpG island methylator phenotype (46.2 and 42.9%). However, they differed in the presence of hMLH1 methylation (7.7 vs 57.1%, p < 0.05). Otherwise, compared with CIN+, MACS had a more frequent CpG island methylator phenotype and MINT1 methylation (p < 0.05) and relatively more common p16 INK4a methylation with marginal significance (p = 0.056).

Conclusion

MACS sporadic colorectal cancers may compose a unique phenotype with distinct clinicopathologic and molecular characteristics.

Keywords

Sporadic Colorectal neoplasms Microsatellite stable Diploid Epigenetics 

Notes

Acknowledgments

This study was supported by grant no. 024072 from the Board of Health of Shanghai, China. We thank the faculty of Molecular Pathological Laboratory, Central Laboratory, Abdominal Surgical Department, and Pathological Department of Cancer Hospital Fudan University for kind assistance with the sample collection, the provision of clinicopathologic data, and the molecular biological experiments.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Guoxiang Cai
    • 1
  • Ye Xu
    • 1
  • Hongfen Lu
    • 2
  • Yingqiang Shi
    • 1
  • Peng Lian
    • 1
  • Junjie Peng
    • 1
  • Xiang Du
    • 2
  • Xiaoyan Zhou
    • 2
  • Zuqing Guan
    • 1
  • Daren Shi
    • 2
  • Sanjun Cai
    • 1
  1. 1.Department of Abdominal Surgery, Cancer HospitalFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Department of Pathology, Molecular Pathological Laboratory, Cancer HospitalFudan UniversityShanghaiPeople’s Republic of China

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