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p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma.
- Source :
-
The Journal of pathology [J Pathol] 1998 Mar; Vol. 184 (3), pp. 265-71. - Publication Year :
- 1998
-
Abstract
- p21WAF1/Cip1 is an inhibitor of cdk/cyclin complexes, and thus regulates the cell cycle. p21 is also related to cell differentiation and is regulated by wild-type p53, although p53-independent regulatory pathways have been proposed. In order to analyse p21 expression as well as its relationship with p53 in human breast cancer, an immunohistochemical analysis was undertaken of 77 breast carcinomas, 16 of them with an in situ component; 30 adjacent normal tissue samples; and five non-neoplastic specimens. Forty-four infiltrating carcinomas (57 per cent) were p21-positive. Expression of p21 was also observed in pre-invasive lesions, whereas normal ducts were negative or focally and weakly positive. p21 expression was associated with high histological grade (II + III) (P = 0.017) and poor tubule formation (P = 0.002), and was significantly less frequent in lobular carcinomas (P = 0.0001). p21 positivity also correlated with increased proliferation, but this seemed to be dependent on the histological grade. Twenty carcinomas (26 per cent) showed p53 overexpression, but this was not associated with p21 negativity, suggesting the existence of p53-independent mechanisms for p21 regulation in vivo. Cyclin D1CCND1 expression was analysed in the same series and an association between p21 and cyclin D1 expression was found, since 23 of 26 cyclin D1-positive carcinomas were p21-positive (P < 0.001 ...). In conclusion, p21 is frequently overexpressed in breast carcinomas and this occurs in the early stages of neoplastic progression. This overexpression seems to be independent of p53 status and might be involved in cyclin D1 modulation.
- Subjects :
- Blotting, Western
Breast Neoplasms pathology
Carcinoma, Ductal, Breast metabolism
Carcinoma, Ductal, Breast pathology
Carcinoma, Lobular metabolism
Carcinoma, Lobular pathology
Cell Differentiation
Cell Division
Cyclin-Dependent Kinase Inhibitor p21
Disease Progression
Female
Humans
Immunoenzyme Techniques
Tumor Suppressor Protein p53 metabolism
Breast Neoplasms metabolism
Cyclin D1 metabolism
Cyclins metabolism
Neoplasm Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3417
- Volume :
- 184
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 9614378
- Full Text :
- https://doi.org/10.1002/(SICI)1096-9896(199803)184:3<265::AID-PATH8>3.0.CO;2-8