Apoptotic index correlates to bcl-2 and p53 protein expression, histological grade and prognosis in invasive breast cancers.

Apoptosis is considered to play a critical role in tumorigenesis. In order to clarify the significance of apoptosis in breast cancers, we quantitated apoptotic cells by light microscopy in 126 patients with invasive breast cancers. The expression of bcl-2, and p53, as regulators of apoptosis, was immunohistochemically analyzed. Apoptotic index (AI) detected in the patients ranged from 0 to 48 per mm2 of breast cancer cells (mean +/- SE, 11.0 +/- 0.97). Significantly highly AI was found for the tumors with grade 3 (p < 0.0001), high mitotic index (p < 0.0001), and bcl-2 negatively (p = 0.004) compared with those with grade 1 or 2, low mitotic index, and bcl-2 expression, respectively. Moreover, high AI was associated with larger tumor size (p = 0.008), positive lymph nodes (p = 0.01), p53 positivity (p = 0.01), and advanced TNM stage (p = 0.03). In survival analysis, we found that low AI, like bcl-2 and other conventional prognostic indicators, was significantly predictive of better prognosis in terms of both disease-free survival (DFS) and overall survival (OS) (each, p < 0.0001). In multivariate analysis, AI failed to retain an independent significant value for DFS or OS. Our results indicate that low AI is related to a number of clinicopathologic and biologic parameters known to predict a lower risk of recurrence and is associated with a favourable survival in invasive breast cancer. However, it was not an independent prognostic factor for clinical outcome in this patient series.