Expression of cell cycle regulatory proteins in the multistep process of oesophageal carcinogenesis:: stepwise over-expression of cyclin E and p53, reduction of p21WAF1/CIP1 and dysregulation of cyclin D1 and p27KIP1

被引:39
作者
Ohbu, M
Kobayashi, N
Okayasu, I
机构
[1] Kitasato Univ, Sch Allied Hlth Sci, Dept Pathol, Kanagawa 2288555, Japan
[2] Kitasato Univ, Sch Med, Dept Surg, Sagamihara, Kanagawa 228, Japan
[3] Kitasato Univ, Sch Med, Dept Pathol, Sagamihara, Kanagawa 228, Japan
关键词
oesophagus; dysplasia; carcinogenesis; cell cycle regulatory proteins; immunohistochemistry;
D O I
10.1046/j.1365-2559.2001.01279.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aims: Cell cycle regulatory proteins were analysed by immunohistochemistry in order to clarify how their expression changes with the degree of atypia as oesophageal surface squamous epithelium progresses from normal mucosa, through reactive change, low-grade dysplasia, and high-grade dysplasia to mucosal invasive carcinoma. Methods and results: Immunostaining for cyclin DI, cyclin E, p21, p27, p53 and Ki67 proteins was performed using 22 normal mucosa, 17 reactive change, 22 low-grade dysplasia, 15 high-grade dysplasia and 22 mucosal invasive carcinoma specimens. Normal mucosa, low-grade dysplasia and high-grade dysplasia samples were taken from patients without any oesophageal invasive carcinoma by endoscopic biopsy or endoscopic mucosal resection, and reactive change and mucosal invasive carcinoma were obtained from oesophagectomy material. Stepwise over-expression of cyclin E (P<0.0001) and p53 (P<0.0001), reduction of p21 (P=0.0189) and dysregulation of cyclin D1 and p27 were observed in the multistep process of oesophageal carcinogenesis. Significant differences in expression of p27 (P<0.0001), p53 (P=0.0299) and Ki67 (P=0.0101) were observed between reactive change and low-grade dysplasia. Furthermore, expression of cyclin D1, cyclin E, p27 and p53 in mucosal invasive carcinoma were significantly different from those in high-grade dysplasia (P=0.0079, P=0.0237, P=0.0042 and P=0.0299, respectively). Conclusions: Cell cycle regulatory proteins, cyclin E, p53 and p21 show stepwise over-expression or reduction with progression of oesophageal carcinogenesis, correlating with the increased cell proliferation observed with Ki67 labelling. We conclude that immunohistochemical analysis for p27, p53 and Ki67 is practically useful for the discrimination between low-grade dysplasia and reactive change. Cyclin D1, cyclin E, p27 and p53 help to distinguish high-grade dysplasia from mucosal invasive carcinoma.
引用
收藏
页码:589 / 596
页数:8
相关论文
共 29 条
  • [1] Anayama T, 1998, INT J CANCER, V79, P439, DOI 10.1002/(SICI)1097-0215(19980821)79:4<439::AID-IJC22>3.0.CO
  • [2] 2-Z
  • [3] BENNETT WP, 1991, ONCOGENE, V6, P1779
  • [4] DEGRADATION OF NUCLEAR ONCOPROTEINS BY THE UBIQUITIN SYSTEM INVITRO
    CIECHANOVER, A
    DIGIUSEPPE, JA
    BERCOVICH, B
    ORIAN, A
    RICHTER, JD
    SCHWARTZ, AL
    BRODEUR, GM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (01) : 139 - 143
  • [5] Increased expression of the p27(KIP1) protein in human esophageal cancer cell lines that over-express cyclin D1
    Doki, Y
    Imoto, M
    Han, EKH
    Sgambato, A
    Weinstein, IB
    [J]. CARCINOGENESIS, 1997, 18 (06) : 1139 - 1148
  • [6] Cyclin-dependent kinase inhibitor p27KIP1 is expressed preferentially in early stages of urothelial carcinoma
    Franke, KH
    Miklosi, M
    Goebell, P
    Clasen, S
    Steinhoff, C
    Anastasiadis, AG
    Gerharz, CD
    Schulz, WA
    [J]. UROLOGY, 2000, 56 (04) : 689 - 695
  • [7] GAO HK, 1994, CANCER RES, V54, P4342
  • [8] ITAKURA Y, 1994, MODERN PATHOL, V7, P867
  • [9] Koga Y, 1996, CANCER, V77, P237, DOI 10.1002/(SICI)1097-0142(19960115)77:2<237::AID-CNCR3>3.0.CO
  • [10] 2-J