Apoptosis in breast carcinomas detected with monoclonal antibody to single-stranded DNA: relation to bcl-2 expression, hormone receptors, and lymph node metastases.
Apoptosis in breast carcinomas detected with monoclonal antibody to single-stranded DNA: relation to bcl-2 expression, hormone receptors, and lymph node metastases.
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发表时间：
1997-03
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通讯作者：
O. Frankfurt;J. Robb;E. Sugarbaker;L. Villa
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作者：
O. Frankfurt;J. Robb;E. Sugarbaker;L. Villa
为了确定细胞凋亡在肿瘤生长、预后和治疗中的作用，有必要对实体瘤中的凋亡细胞进行精确的定量。本研究用抗单链DNA的单抗(MAb)对91例乳腺癌组织切片进行染色，用一种新的细胞凋亡标记物测定了乳腺癌的细胞凋亡性死亡强度。用单抗对凋亡细胞进行染色，反映了核蛋白消化引起的DNA热稳定性的降低，这一点在加热前与组蛋白重组的切片中消除了染色。用单抗分析细胞凋亡具有很高的敏感性和特异性，这是基于蛋白水解酶的激活在细胞凋亡的机制和控制中的中心作用。乳腺癌的细胞凋亡指数(AIs)在0~46%之间。大多数癌的AAI较低，而29例被归类为高度凋亡的癌(AI>；/=10%)。高水平的细胞凋亡性死亡与bcl2蛋白表达阴性、雌孕激素受体丢失、S期细胞比例高以及淋巴结转移风险增加有关。AI与肿瘤大小及P53免疫组化染色均无相关性。在原发癌中细胞凋亡率高的患者中有59%的患者有淋巴结转移，而在原发癌中AIS低于10%的患者中只有21%的患者有淋巴转移。因此，单抗分析的高灵敏度使其有可能识别出具有强烈细胞凋亡和预后不良标志的乳腺癌亚群。这些结果表明，乳腺癌中细胞凋亡的检测提供了有价值的预后信息。
Precise quantitation of apoptotic cells in solid tumors is necessary to determine the role of apoptosis in cancer growth, prognosis, and treatment. In this study, the intensity of apoptotic death was determined in 91 breast carcinomas with a novel cellular marker of apoptosis based on the staining of histological sections with a monoclonal antibody (MAb) to single-stranded DNA. Staining of apoptotic cells with the MAb reflected the decreased thermal stability of DNA induced by the digestion of nuclear proteins, as demonstrated by the elimination of staining in sections reconstituted with histones before heating. The high sensitivity and specificity of apoptosis analysis with the MAb is based on the central role of protease activation in the mechanism and control of apoptosis. Apoptotic indexes (AIs) in breast carcinomas ranged between 0 and 46%. Most of the carcinomas had relatively low AIs, whereas 29 cases were classified as carcinomas with intensive apoptosis (AI >/= 10%). The high level of apoptotic cell death was associated with negative immunostaining for bcl-2 protein, the loss of estrogen and progesterone receptors, high proportion of cells in S-phase, and increased risk of lymph node metastases. There was no correlation between AI and tumor size or p53 immunostaining. Lymph node metastases were detected in 59% of patients with high levels of apoptosis in primary carcinomas and in only 21% of patients with AIs below 10% in primary carcinomas. Thus, the high sensitivity of the MAb assay made it possible to identify a subset of breast carcinomas with intensive apoptosis and markers of poor prognosis. These results demonstrate that the measurement of apoptosis in breast carcinomas provides valuable prognostic information.