p53, mitosis, apoptosis and necrosis as prognostic indicators of long-term survival in breast cancer.

This study was designed to evaluate the prognostic importance of p53, mitosis, apoptosis and necrosis with long-term follow-up in Japanese patients with breast cancer. Four hundred and twenty-two patients with breast cancer were studied. We investigated 7 factors, including p53, mitotic index (MI), apoptotic index (AI), necrosis, lymph-node status (n), clinical tumor size (T) and lymphatic vessel invasion, followed for a median of 10 years. p53 accumulation was found in 30.1%, MI in 35.2%, AI in 36.3% and necrosis in 38.5%. p53 accumulation was correlated with MI (p = 0.0324), AI (p = 0.0010), necrosis (p = 0.0003), T (p = 0.0320), n (p < 0.0001), estrogen receptor (p = 0.0005) and progesterone receptor (p = 0.0287). Univariate analysis showed that p53, MI and necrosis were significantly predictive of 20-year overall survival (OS) or of 20-year relapse-free survival (RFS) (p < 0.0001 or p = 0.0003, p< 0.0001 or p < 0.0001 and p = 0.0131 or p = 0.0068, respectively), but AI was not. Multivariate analysis showed that p53 was an independent prognostic factor with RFS in all the patients, especially, with relapse-free survival (RFS) in the patients with T1 and with RFS and overall survival (OS) in the patients with a node-negative tumor. MI was an independent prognostic factor with OS in all the patients and with RFS and OS in the patients with a node-negative tumor. However, AI and necrosis were not independent predictors.