Clinicopathologic and molecular features of sporadic microsatellite- and chromosomal-stable colorectal cancers
- First Online:
- Cite this article as:
- Cai, G., Xu, Y., Lu, H. et al. Int J Colorectal Dis (2008) 23: 365. doi:10.1007/s00384-007-0423-7
- 130 Downloads
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 p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 with methylation-specific polymerase chain reaction.
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 p16INK4a methylation with marginal significance (p = 0.056).
MACS sporadic colorectal cancers may compose a unique phenotype with distinct clinicopathologic and molecular characteristics.