Replication error phenotype, clinicopathological variables, and patient outcome in Dukes' B stage II (T3,N0,M0) colorectal cancer

被引:40
作者
Curran, B
Lenehan, K
Mulcahy, H
Tighe, O
Bennett, MA
Kay, EW
O'Donoghue, DP
Leader, M
Croke, DT
机构
[1] Royal Coll Surg Ireland, Dept Biochem, Dublin 2, Ireland
[2] Royal Coll Surg Ireland, Dept Pathol, Dublin 2, Ireland
[3] St Vincents Univ Hosp, Gastroenterol & Liver Unit, Dublin, Ireland
关键词
colon cancer; replication error phenotype; microsatellite instability; c-Ki-ras mutation; p53; expression; c-erbB-2;
D O I
10.1136/gut.46.2.200
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Aims--To examine the relation between the replication error (RER) phenotype and other genetic events, clinical features, Dukes' B stage II (T3,NO,MO) colorectal cancer. Methods--RER phenotype was investigated in 159 patients by PCR amplification of microsatellite marker loci on chromoparaffin wax embedded tissue. Results--Of 159 colorectal cancers studied, 22 (14%) were RER+ while 137 (86%) were RER- for two or more loci. RER+ tumours were more commonly located in the right colon, tended to be larger than poorly differentiated than RER- cancers. No significant associations were seen between RER status and the presence of a long term survival and other genetic events, clinical features, and long term survival in patients with Dukes' B stage II (T3,N0,M0) colorectal of microsatellite marker loci on chromosomes 5q, 17p, 17q, and 18q from tumour DNA extracted from archival tissue. Data on activating c-Ki-ras mutations were available from a previous study. Immunohistochemical detection of p53 and c-erbB-2 expression was performed on paraffin wax embedded tissue, the right colon, tended to be larger than RER- tumours, and were more often poorly differentiated than RER- cancers, between RER status and the presence of a mutant c-Ki-ras gene, or between RER status and p53, c-erbB-2, or c-myc gene expression. Univariate survival analysis showed that outcome was similar in RER+ and RER- cases. Multivariate survival analysis showed that the relative risk of death for patients with RER+ cancers was 0.95 that of patients with RER- cancers. Conclusions--The results suggest that, while the RER phenotype may be associated with some differences in tumour pathology (site, size, differentiation), it is not associated with the genetic alterations studied or with significant differences in long term survival.
引用
收藏
页码:200 / 204
页数:5
相关论文
共 45 条
[31]   INACTIVATION OF THE TYPE-II TGF-BETA RECEPTOR IN COLON-CANCER CELLS WITH MICROSATELLITE INSTABILITY [J].
MARKOWITZ, S ;
WANG, J ;
MYEROFF, L ;
PARSONS, R ;
SUN, LZ ;
LUTTERBAUGH, J ;
FAN, RS ;
ZBOROWSKA, E ;
KINZLER, KW ;
VOGELSTEIN, B ;
BRATTAIN, M ;
WILLSON, JKV .
SCIENCE, 1995, 268 (5215) :1336-1338
[32]  
Meuth M, 1996, CANCER SURV, V28, P33
[33]   MUTATIONS OF 2 PMS HOMOLOGS IN HEREDITARY NONPOLYPOSIS COLON-CANCER [J].
NICOLAIDES, NC ;
PAPADOPOULOS, N ;
LIU, B ;
WEI, YF ;
CARTER, KC ;
RUBEN, SM ;
ROSEN, CA ;
HASELTINE, WA ;
FLEISCHMANN, RD ;
FRASER, CM ;
ADAMS, MD ;
VENTER, JC ;
DUNLOP, MG ;
HAMILTON, SR ;
PETERSEN, GM ;
DELACHAPELLE, A ;
VOGELSTEIN, B ;
KINZLER, KW .
NATURE, 1994, 371 (6492) :75-80
[34]   GENETIC-MAPPING OF A LOCUS PREDISPOSING TO HUMAN COLORECTAL-CANCER [J].
PELTOMAKI, P ;
AALTONEN, LA ;
SISTONEN, P ;
PYLKKANEN, L ;
MECKLIN, JP ;
JARVINEN, H ;
GREEN, JS ;
JASS, JR ;
WEBER, JL ;
LEACH, FS ;
PETERSEN, GM ;
HAMILTON, SR ;
DELACHAPELLE, A ;
VOGELSTEIN, B .
SCIENCE, 1993, 260 (5109) :810-812
[35]  
Peltomaki P, 1997, ADV CANCER RES, V71, P93, DOI 10.1016/S0065-230X(08)60097-4
[36]   DINUCLEOTIDE REPEAT POLYMORPHISM IN THE HUMAN DCC GENE AT CHROMOSOME 18Q21 [J].
RISINGER, JI ;
BOYD, J .
HUMAN MOLECULAR GENETICS, 1992, 1 (08) :657-657
[37]  
SANTOS GF, 1988, J BIOL CHEM, V263, P9565
[38]   Microsatellite instability in the insulin-like growth factor II receptor gene in gastrointestinal tumours [J].
Souza, RF ;
Appel, R ;
Yin, J ;
Wang, SN ;
Smolinski, KN ;
Abraham, JM ;
Zou, TT ;
Shi, YQ ;
Lei, JY ;
Cottrell, J ;
Cymes, K ;
Biden, K ;
Simms, L ;
Leggett, B ;
Lynch, PM ;
Frazier, M ;
Powell, SM ;
Harpaz, N ;
Sugimura, H ;
Young, J ;
Meltzer, SJ .
NATURE GENETICS, 1996, 14 (03) :255-257
[39]   A CA REPEAT 30-70 KB DOWNSTREAM FROM THE ADENOMATOUS POLYPOSIS-COLI (APC) GENE [J].
SPIRIO, L ;
JOSLYN, G ;
NELSON, L ;
LEPPERT, M ;
WHITE, R .
NUCLEIC ACIDS RESEARCH, 1991, 19 (22) :6348-6348
[40]   MICROSATELLITE INSTABILITY IN CANCER OF THE PROXIMAL COLON [J].
THIBODEAU, SN ;
BREN, G ;
SCHAID, D .
SCIENCE, 1993, 260 (5109) :816-819