DNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: a mild mutator pathway for colorectal cancer?

被引:269
作者
Iino, H
Jass, JR [1 ]
Simms, LA
Young, J
Leggett, B
Ajioka, Y
Watanabe, H
机构
[1] Univ Queensland, Sch Med, Dept Pathol, Herston, Qld 4006, Australia
[2] Yamanashi Med Univ, Dept Surg 1, Yamanashi, Japan
[3] Royal Brisbane Hosp, Bancroft Ctr, Conjoint Gastroenterol Lab, Brisbane, Qld, Australia
[4] Niigata Univ, Dept Pathol 1, Niigata, Japan
关键词
polyp; colorectum; microsatellite instability; serrated adenoma;
D O I
10.1136/jcp.52.1.5
中图分类号
R36 [病理学];
学科分类号
100104 [病理学与病理生理学];
摘要
Aim-To investigate the distribution of DNA microsatellite instability (MSI) in a series of hyperplastic polyps, serrated adenomas, and mixed polyps of the colorectum. Methods-DNA was extracted from samples of 73 colorectal polyps comprising tubular adenomas (23), hyperplastic polyps (21), serrated adenomas (17), and mixed polyps (12). The presence of MSI was investigated at six loci: MYCL, D2S123, F13B, BAT-40, BAT-26, and c-myb T22, using polymerase chain reaction based methodology. MSI cases were classified as MSI-Low (MSI-L) and MSI-High (MSI-H), based on the number of affected loci. Results-The frequency of MSI increased in tubular adenomas (13%), hyperplastic polyps (29%), serrated adenomas (53%), and mixed polyps (83%) (Wilcoxon rank sum statistic, p < 0.001). Hyperplastic epithelium was present in nine of 12 mixed polyps and showed MSI in eight of these. MSI was mostly MSI-L. MSI-H occurred in two serrated adenomas and three mixed polyps. Clonal relations were demonstrated between hyperplastic and dysplastic epithelium in four of eight informative mixed polyps. Conclusions-The findings support the view that hyperplastic polyps may be fundamentally neoplastic rather than hyperplastic. A proportion of hyperplastic polyps may serve as a precursor of a subset (10%) of colorectal cancers showing the MSI-L phenotype, albeit through the intermediate step of serrated dysplasia. This represents a novel and distinct morphogenetic pathway for colorectal cancer.
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收藏
页码:5 / 9
页数:5
相关论文
共 36 条
[1]
AALTONEN LA, 1994, CANCER RES, V54, P1645
[2]
CLUES TO THE PATHOGENESIS OF FAMILIAL COLORECTAL-CANCER [J].
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 .
SCIENCE, 1993, 260 (5109) :812-816
[3]
Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum [J].
Ajioka, Y ;
Watanabe, H ;
Jass, JR ;
Yokota, Y ;
Kobayashi, M ;
Nishikura, K .
GUT, 1998, 42 (05) :680-684
[4]
BARDI G, 1993, CANCER RES, V53, P1895
[5]
Dietmaier W, 1997, CANCER RES, V57, P4749
[6]
Grady WM, 1998, CANCER RES, V58, P3101
[7]
GENETIC INSTABILITY ASSOCIATED WITH ADENOMA TO CARCINOMA PROGRESSION IN HEREDITARY NONPOLYPOSIS COLON-CANCER [J].
JACOBY, RF ;
MARSHALL, DJ ;
KAILAS, S ;
SCHLACK, S ;
HARMS, B ;
LOVE, R .
GASTROENTEROLOGY, 1995, 109 (01) :73-82
[8]
EVOLUTION OF HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER [J].
JASS, JR ;
STEWART, SM .
GUT, 1992, 33 (06) :783-786
[9]
Morphology of sporadic colorectal cancer with DNA replication errors [J].
Jass, JR ;
Do, KA ;
Simms, LA ;
Iino, H ;
Wynter, C ;
Pillay, SP ;
Searle, J ;
Radford-Smith, G ;
Young, J ;
Leggett, B .
GUT, 1998, 42 (05) :673-679
[10]
Mixed epithelial polyps in association with hereditary non-polyposis colorectal cancer providing an alternative pathway of cancer histogenesis [J].
Jass, JR ;
Cottier, DS ;
Pokos, V ;
Parry, S ;
Winship, IM .
PATHOLOGY, 1997, 29 (01) :28-33