p21(Waf1/Cip1) and p53 protein expression in breast cancer

Am J Clin Pathol. 1997 Jun;107(6):684-91. doi: 10.1093/ajcp/107.6.684.


p21/Cip1/Waf1 (wild-type p53 activated fragment 1/cyclin-dependent kinase [Cdk]-interacting protein 1) is a prominent Cdk inhibitor and has been shown to be a downstream mediator of p53. In this study, we sought to clarify the clinical significance of Waf1 and the relationship between Waf1 and p53 in breast cancer. For this purpose, the expressions of Waf1 and p53 were evaluated immunohistochemically in a series of 104 patients. Waf1 was expressed in 51 (49%) of 104 tumors tested, and p53 in 33 tumors (32%). Inverse expression of these two proteins was seen in 76 cases (73%); 47 were Waf1-positive and p53-negative, and 29 were Waf1-negative and p53-positive. A comparison with clinicopathologic parameters showed that Waf1 expression correlated with negative lymph nodes (P<.01), a low histologic grade (P<.0001), and positive estrogen receptor status (P<.01). Recurrence-free survival was lower for patients with Waf1-negative tumors than for those with Waf1-positive tumors (P<.0001). In multivariate analysis, Waf1 expression and low histologic grade (1 or 2) tumors had an independent prognostic significance for recurrence-free survival. These results suggest that Waf1 is induced mainly by a p53-dependent pathway and could be a reliable indicator of recurrence in breast cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Medullary / metabolism*
  • Carcinoma, Medullary / pathology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis*
  • Enzyme Inhibitors / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology
  • Tumor Suppressor Protein p53 / biosynthesis*


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Inhibitors
  • Tumor Suppressor Protein p53