p21(WAF1/Cip1) is associated with cyclin D1(CCND1) expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma

MJ Rey, PL Fernandez*, P Jares, M Munoz, A Nadal, N Peiro, Iracema Nayach, C Mallofre, J Muntane, E Campo, J Estape, A Cardesa

*Corresponding author for this work

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50 Citations (Scopus)

Abstract

p21(WAF1/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 D1(CCND1) 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

Original languageEnglish
Pages (from-to)265-271
Number of pages7
JournalJ. Pathol.
Volume184
Issue number3
DOIs
Publication statusPublished - Mar 1998

Keywords

  • breast
  • WAF1
  • p21
  • p53
  • CCND1
  • cyclin D1
  • DEPENDENT KINASE INHIBITORS
  • TUMOR-SUPPRESSOR GENE
  • P53-INDEPENDENT EXPRESSION
  • EPITHELIAL-CELLS
  • DNA-REPLICATION
  • PROGNOSTIC VALUE
  • P21
  • CANCER
  • MUTATION
  • PROTEIN

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