Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers

被引:287
作者
Halling, KC
French, AJ
McDonnell, SK
Burgart, LJ
Schaid, DJ
Peterson, BJ
Moon-Tasson, L
Mahoney, MR
Sargent, DJ
O'Connell, MJ
Witzig, TE
Farr, GH
Goldberg, RM
Thibodeau, SN
机构
[1] Mayo Clin & Mayo Fdn, Genet Lab, Dept Lab Med, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Dept Pathol, Rochester, MN 55905 USA
[3] Mayo Clin & Mayo Fdn, Biostat Sect, Rochester, MN 55905 USA
[4] Mayo Clin & Mayo Fdn, Div Hematol, Rochester, MN 55905 USA
[5] N Cent Canc Treatment Grp, Rochester, MN USA
来源
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 1999年 / 91卷 / 15期
关键词
D O I
10.1093/jnci/91.15.1295
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Microsatellite instability (MSI) and allelic imbalance involving chromosome arms 5q, 8p, 17p, and 18q are genetic alterations commonly found in colorectal cancer. We investigated whether the presence or absence of these genetic alterations would allow stratification of patients with Astler-Coller stage B2 or C colorectal cancer into favorable and unfavorable prognostic groups. Methods: Tumors from 508 patients were evaluated for MSI and allelic imbalance by use of 11 microsatellite markers located on chromosome arms 5q, 8p, 15q, 17p, and 18q, Genetic alterations involving each of these markers were examined for associations with survival and disease recurrence. All P values are two-sided. Results: In univariate analyses, high MSI (MSI-H), i.e., MSI at 30% or more of the loci examined, was associated with improved survival (P = .02) and time to recurrence (P = .01), The group of patients whose tumors exhibited allelic imbalance at chromosome 8p had decreased survival (P = .02) and time to recurrence (P = .004), No statistically significant associations with survival or time to recurrence were observed for markers on chromosome arms 5q, 15q, 17p,Or 18q, In multivariate analyses, MSI-H was an independent predictor of improved survival (hazard ratio [HP] = 0.51; 95% confidence interval [CI] = 0.31-0.82; P = .006) and time to recurrence (HR = 0.42; 95% CI = 0.24-0.74; P = .003), and 8p allelic imbalance was an independent predictor of decreased survival (HR = 1.89; 95% CI = 1.25-2.83; P = .002) and time to recurrence (HR = 2.07; 95% CI = 1.32-3.25; P = .002), Conclusions: Patients whose tumors exhibited MSI-H had a favorable prognosis, whereas those with 8p allelic imbalance had a poor prognosis; both alterations served as independent prognostic factors, To our knowledge, this is the first report of an association between 8p allelic imbalance and survival in patients with colorectal cancer.
引用
收藏
页码:1295 / 1303
页数:9
相关论文
共 83 条
  • [1] CLUES TO THE PATHOGENESIS OF FAMILIAL COLORECTAL-CANCER
    AALTONEN, LA
    PELTOMAKI, P
    LEACH, FS
    SISTONEN, P
    PYLKKANEN, L
    MECKLIN, JP
    JARVINEN, H
    POWELL, SM
    JEN, J
    HAMILTON, SR
    PETERSEN, GM
    KINZLER, KW
    VOGELSTEIN, B
    DELACHAPELLE, A
    [J]. SCIENCE, 1993, 260 (5109) : 812 - 816
  • [2] [Anonymous], 1989, SAS STAT US GUID VER
  • [3] THE PROGNOSTIC SIGNIFICANCE OF DIRECT EXTENSION OF CARCINOMA OF THE COLON AND RECTUM
    ASTLER, VB
    COLLER, FA
    [J]. ANNALS OF SURGERY, 1954, 139 (06) : 846 - 852
  • [4] BAKER SJ, 1990, CANCER RES, V50, P7717
  • [5] BEART RW, 1990, ARCH SURG-CHICAGO, V125, P897
  • [6] BOVA GS, 1993, CANCER RES, V53, P3869
  • [7] Bubb VJ, 1996, ONCOGENE, V12, P2641
  • [8] CAMPO E, 1994, CANCER-AM CANCER SOC, V73, P2913, DOI 10.1002/1097-0142(19940615)73:12<2913::AID-CNCR2820731207>3.0.CO
  • [9] 2-L
  • [10] CAMPO E, 1991, CANCER RES, V51, P4436