title: Clinicopathologic and molecular features of sporadic microsatellite- and chromosomal-stable colorectal cancers.
abstract: OBJECTIVE
  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.
  
  
  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 pl4ARF, hMLH1, p161NK4a 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 p161IK4a methylation with marginal significance (p= 0 .056).
  
  
  CONCLUSIONS
  MACS sporadic colorectal cancers may compose a unique phenotype with distinct clinicopathologic and molecular characteristics.
authors.affiliation: Department of Abdominal Surgery, Cancer Hospital, Fudan University, 270 Dong An Road, Shanghai 200032, People's Republic of China.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Cai
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Hongfen
authors.initials: H
authors.lastname: Lu
authors.forename: Yingqiang
authors.initials: Y
authors.lastname: Shi
authors.forename: Peng
authors.initials: P
authors.lastname: Lian
authors.forename: Junjie
authors.initials: J
authors.lastname: Peng
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.forename: Zuqing
authors.initials: Z
authors.lastname: Guan
authors.forename: Daren
authors.initials: D
authors.lastname: Shi
authors.forename: Sanjun
authors.initials: S
authors.lastname: Cai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D043171:Chromosomal Instability / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D004171:Diploidy; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C494826:BAX protein, human; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D051028:bcl-2-Associated X Protein; D000070957:MutL Protein Homolog 1