Gandhi A, Holland P A, Knox W F, Potten C S, Bundred N J
University Department of Surgery, University Hospital of South Manchester, UK.
Br J Cancer. 1998 Sep;78(6):788-94. doi: 10.1038/bjc.1998.580.
Following breast-conserving surgery for ductal carcinoma in situ (DCIS), the presence of comedo necrosis reportedly predicts for higher rates of post-operative recurrence. To examine the role of programmed cell death (apoptosis) in the aetiology of the cell death described as comedo necrosis, we studied 58 DCIS samples, using light microscopy, for morphological evidence of apoptotic cell death. The percentage of apoptotic cells (apoptotic index, AI) was compared between DCIS with and without evidence of 'comedo necrosis' and related to the immunohistochemical expression of the anti-apoptosis gene bcl-2, mitotic index (MI), the cellular proliferation antigen Ki67, nuclear grade and oestrogen receptor (ER) status. AI was significantly higher in DCIS samples displaying high-grade comedo necrosis than in low-grade non-comedo samples: median AI = 1.60% (range 0.84-2.89%) and 0.45% (0.1-1.31%) respectively (P < 0.001). Increasing nuclear grade correlated positively with AI (P < 0.001) and negatively with bcl-2 expression (P = 0.003). Bcl-2 correlated negatively with AI (P = 0.019) and strongly with ER immunoreactivity (P < 0.001). Cellular proliferation markers (MI and Ki67 immunostaining) correlated strongly with AI and were higher in comedo lesions 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 associated with a high apoptotic rate. It is likely that dysregulation of proliferation/apoptosis control mechanisms accounts for the more malignant features typical of ER negative comedo DCIS.
据报道，原位导管癌（DCIS）保乳手术后，粉刺状坏死的存在预示着术后复发率较高。为了研究程序性细胞死亡（凋亡）在被描述为粉刺状坏死的细胞死亡病因中的作用，我们使用光学显微镜研究了58例DCIS样本，以寻找凋亡细胞死亡的形态学证据。比较了有和没有“粉刺状坏死”证据的DCIS之间的凋亡细胞百分比（凋亡指数，AI），并将其与抗凋亡基因bcl-2的免疫组化表达、有丝分裂指数（MI）、细胞增殖抗原Ki67、核分级和雌激素受体（ER）状态相关联。显示高级别粉刺状坏死的DCIS样本中的AI显著高于低级别非粉刺状样本：中位AI分别为1.60%（范围0.84 - 2.89%）和0.45%（0.1 - 1.31%）（P < 0.001）。核分级增加与AI呈正相关（P < 0.001），与bcl-2表达呈负相关（P = 0.003）。Bcl-2与AI呈负相关（P = 0.019），与ER免疫反应性呈强相关（P < 0.001）。细胞增殖标志物（MI和Ki67免疫染色）与AI强烈相关，在粉刺状病变和高核分级肿瘤中更高（所有病例P < 0.001）。因此，凋亡对ER阴性、高级别DCIS中所描述的细胞死亡有显著贡献，其中高增殖率与高凋亡率相关。增殖/凋亡控制机制的失调可能是ER阴性粉刺状DCIS典型的更恶性特征的原因。
