EVIDENCE OF SIGNIFICANT APOPTOSIS IN POORLY DIFFERENTIATED DUCTAL CARCINOMA IN-SITU OF THE BREAST

Following breast-conserving surgery for ductal carcinoma in situ (DCIS ), the presence of comedo necrosis reportedly predicts for higher rate s of post-operative recurrence. To examine the role of programmed cell death (apoptosis) in the aetiology of the cell death described as com edo necrosis, we studied 58 DCIS samples, using light microscopy, for morphological evidence of apoptotic cell death. The percentage of apop totic cells (apoptotic index, Al) was compared between DCIS with and w ithout evidence of 'comedo necrosis' and related to the immunohistoche mical expression of the anti-apoptosis gene bcl-2, mitotic index (MI), the cellular proliferation antigen Ki67, nuclear grade and oestrogen receptor (ER) status. Al was significantly higher in DCIS samples disp laying high-grade comedo necrosis than in low-grade non-comedo samples : median Al = 1.60% (range 0.84-2.89%) and 0.45% (0.1-1.31%) respectiv ely (P < 0.001). Increasing nuclear grade correlated positively with A l (P < 0.001) and negatively with bcl-2 expression (P = 0.003). Bcl-2 correlated negatively with Al (P = 0.019) and strongly with ER immunor eactivity (P < 0.001). Cellular proliferation markers (MI and Ki67 imm unostaining) correlated strongly with Al and were higher in comedo les ions and tumours of high nuclear grade (P < 0.001 in all cases). Thus, apoptosis contributes significantly to the cell death described in ER -negative, high-grade DCIS in which a high proliferative rate is assoc iated with a high apoptotic rate. It is likely that dysregulation of p roliferation/apoptosis control mechanisms accounts for the more malign ant features typical of ER negative comedo DCIS.