Early alteration of cell-cycle-regulated gene expression in colorectal neoplasia

Kornelia Polyak, Stanley R. Hamilton, Bert Vogelstein, Kenneth W Kinzler

Research output: Contribution to journalArticle

Abstract

Aberrant crypt foci with dysplasia are thought to be the first detectable lesions of colorectal neoplasia. Because cell cycle disruption appears crucial for tumorigenesis, we analyzed the immunohistochemical expression patterns of the prototype cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and the proliferation marker Ki67 in the early stages of colorectal tumorigenesis. In colorectal epithelium, p21(WAF1/CIP1) expression was undetectable in the lower third of the crypts, where Ki67 was expressed, but then sharply increased as cells passed out of the proliferating zone and migrated toward the lumen. Hyperplastic polyps retained this normal compartmentalized pattern. In contrast, markedly decreased p21(WAF1/CIP1) immunostaining was observed in dysplastic aberrant crypt foci as well as in small adenomas. Moreover, the compartmentalization of Ki67 and p21(WAF1/CIP1) was lost, as Ki67 expression extended into the small p21-expressing zone at the top of the crypts. These data suggest that the dysregulated expression of cell-cycle-controlling genes and the consequent release from normal cell cycle controls may represent an essential early step in colorectal neoplasia.

Original languageEnglish (US)
Pages (from-to)381-387
Number of pages7
JournalAmerican Journal of Pathology
Volume149
Issue number2
StatePublished - Aug 1996

Fingerprint

Aberrant Crypt Foci
cdc Genes
Carcinogenesis
Cyclin-Dependent Kinase Inhibitor p21
Gene Expression
Polyps
Cell Cycle Checkpoints
Adenoma
Neoplasms
Cell Cycle
Epithelium

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Early alteration of cell-cycle-regulated gene expression in colorectal neoplasia. / Polyak, Kornelia; Hamilton, Stanley R.; Vogelstein, Bert; Kinzler, Kenneth W.

In: American Journal of Pathology, Vol. 149, No. 2, 08.1996, p. 381-387.

Research output: Contribution to journalArticle

@article{d7366e4a90e04cbe8005db75be01facf,
title = "Early alteration of cell-cycle-regulated gene expression in colorectal neoplasia",
abstract = "Aberrant crypt foci with dysplasia are thought to be the first detectable lesions of colorectal neoplasia. Because cell cycle disruption appears crucial for tumorigenesis, we analyzed the immunohistochemical expression patterns of the prototype cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and the proliferation marker Ki67 in the early stages of colorectal tumorigenesis. In colorectal epithelium, p21(WAF1/CIP1) expression was undetectable in the lower third of the crypts, where Ki67 was expressed, but then sharply increased as cells passed out of the proliferating zone and migrated toward the lumen. Hyperplastic polyps retained this normal compartmentalized pattern. In contrast, markedly decreased p21(WAF1/CIP1) immunostaining was observed in dysplastic aberrant crypt foci as well as in small adenomas. Moreover, the compartmentalization of Ki67 and p21(WAF1/CIP1) was lost, as Ki67 expression extended into the small p21-expressing zone at the top of the crypts. These data suggest that the dysregulated expression of cell-cycle-controlling genes and the consequent release from normal cell cycle controls may represent an essential early step in colorectal neoplasia.",
author = "Kornelia Polyak and Hamilton, {Stanley R.} and Bert Vogelstein and Kinzler, {Kenneth W}",
year = "1996",
month = "8",
language = "English (US)",
volume = "149",
pages = "381--387",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Early alteration of cell-cycle-regulated gene expression in colorectal neoplasia

AU - Polyak, Kornelia

AU - Hamilton, Stanley R.

AU - Vogelstein, Bert

AU - Kinzler, Kenneth W

PY - 1996/8

Y1 - 1996/8

N2 - Aberrant crypt foci with dysplasia are thought to be the first detectable lesions of colorectal neoplasia. Because cell cycle disruption appears crucial for tumorigenesis, we analyzed the immunohistochemical expression patterns of the prototype cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and the proliferation marker Ki67 in the early stages of colorectal tumorigenesis. In colorectal epithelium, p21(WAF1/CIP1) expression was undetectable in the lower third of the crypts, where Ki67 was expressed, but then sharply increased as cells passed out of the proliferating zone and migrated toward the lumen. Hyperplastic polyps retained this normal compartmentalized pattern. In contrast, markedly decreased p21(WAF1/CIP1) immunostaining was observed in dysplastic aberrant crypt foci as well as in small adenomas. Moreover, the compartmentalization of Ki67 and p21(WAF1/CIP1) was lost, as Ki67 expression extended into the small p21-expressing zone at the top of the crypts. These data suggest that the dysregulated expression of cell-cycle-controlling genes and the consequent release from normal cell cycle controls may represent an essential early step in colorectal neoplasia.

AB - Aberrant crypt foci with dysplasia are thought to be the first detectable lesions of colorectal neoplasia. Because cell cycle disruption appears crucial for tumorigenesis, we analyzed the immunohistochemical expression patterns of the prototype cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and the proliferation marker Ki67 in the early stages of colorectal tumorigenesis. In colorectal epithelium, p21(WAF1/CIP1) expression was undetectable in the lower third of the crypts, where Ki67 was expressed, but then sharply increased as cells passed out of the proliferating zone and migrated toward the lumen. Hyperplastic polyps retained this normal compartmentalized pattern. In contrast, markedly decreased p21(WAF1/CIP1) immunostaining was observed in dysplastic aberrant crypt foci as well as in small adenomas. Moreover, the compartmentalization of Ki67 and p21(WAF1/CIP1) was lost, as Ki67 expression extended into the small p21-expressing zone at the top of the crypts. These data suggest that the dysregulated expression of cell-cycle-controlling genes and the consequent release from normal cell cycle controls may represent an essential early step in colorectal neoplasia.

UR - http://www.scopus.com/inward/record.url?scp=0030057835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030057835&partnerID=8YFLogxK

M3 - Article

VL - 149

SP - 381

EP - 387

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 2

ER -