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.