Apoptosis in breast cancer as related to histopathological characteristics and prognosis

Apoptotic cells were quantitated by light microscopy in a series of 288 breast carcinomas, and their number (cells/mm2 of neoplastic epithelium, i.e., the apoptotic index, AI) was related to various histopathological features and disease outcome. High AI was associated with tumour necrosis (P = 0.003), lack of tubule formation (P = 0.03), dense stromal lymphocyte infiltration (P = 0.0009), high grade of the tumour (P < 0.0001), DNA aneuploidy (P = 0.049), high S-phase fraction (P = 0.010), high mitotic rate (P < 0.0001), lack of sex steroid receptors (P = 0.004), expression of p53 tumour suppressor gene (P = 0.004), and high values of morphometrically measured nuclear factors (P < 0.05). In survival analysis, an AI greater than 3/mm2 was related to short recurrence-free survival in the entire cohort (P = 0.0079) as well as in the axillary lymph node-negative tumours (P = 0.0253). Survival of the patients with node-negative tumours (P = 0.0356), node-positive tumours (P = 0.0085) and in the entire cohort (P = 0.004) was related to AI. Recurrence-free survival was related to the mitotic index (P = 0.0012), ductal type (P = 0.011), S.D. of the nuclear area (P = 0.075), and axillary lymph node status (P = 0.096). Cox's analysis showed that only the tumour diameter (P < 0.001), axillary lymph node status (P = 0.001), progesterone receptor content (P = 0.004) and ductal type (P = 0.041) had independent prognostic value, whereas AI did not.