Dressler L G, Seamer L C, Owens M A, Clark G M, McGuire W L
Department of Medicine/Oncology, University of Texas Health Science Center, San Antonio 78284-7884.
Cancer. 1988 Feb 1;61(3):420-7. doi: 10.1002/1097-0142(19880201)61:3<420::aid-cncr2820610303>3.0.co;2-0.
Breast cancer proliferative capacity as determined by the DNA thymidine labeling index, along with estrogen and progesterone receptor status, is highly predictive for risk of relapse and overall survival. Recently, DNA ploidy and proliferative capacity (S-phase fraction [SPF]) as determined by flow cytometry have also shown significant prognostic value. The authors have developed a technique which allows a 50 to 100 mg aliquot of the same frozen breast tumor specimen routinely employed in steroid receptor assays, to be assayed for both DNA ploidy and SPF by flow cytometry. Of the 1331 tumors examined, DNA histograms were evaluable for ploidy in 89% (1184) of specimens examined; 57% of these were aneuploid. Adapting a trapezoidal model to estimate SPF in both diploid and aneuploid tumors, the authors found 81% (1084) to be evaluable for SPF, with a median SPF of 5.8% for the entire population. The median SPF was significantly lower in diploid tumors (2.6%) than in aneuploid tumors (10.3%, P less than 0.0001). Both aneuploidy and high SPF were strongly associated with absence of steroid receptors. Aneuploid tumors showed more striking differences in the frequency of high S-phase values with respect to receptor status and age or menopausal status, whereas diploid but not aneuploid tumors showed lower SPF in node-negative versus node-positive patients. Because it is particularly important to identify the high-risk minority of node-negative patients, the authors examined the node-negative group separately. High SPF subgroups appeared in each category of receptor status and age or menopausal status within the node-negative group, suggesting that SPF will be an independent prognostic factor. With the DNA flow cytometric methods used here, it is now practical to determine ploidy and SPF for nearly every breast cancer patient. These factors, which show associations with established prognostic factors, such as receptor status can now be fully evaluated for their prognostic significance in broad patient populations.
通过DNA胸苷标记指数所确定的乳腺癌增殖能力，连同雌激素和孕激素受体状态，对复发风险和总体生存率具有高度预测性。最近，通过流式细胞术确定的DNA倍性和增殖能力（S期分数[SPF]）也显示出显著的预后价值。作者开发了一种技术，该技术可使在类固醇受体测定中常规使用的同一冷冻乳腺肿瘤标本的50至100毫克等分试样，通过流式细胞术同时检测DNA倍性和SPF。在检查的1331个肿瘤中，89%（1184个）标本的DNA直方图可用于评估倍性；其中57%为非整倍体。采用梯形模型来估计二倍体和非整倍体肿瘤中的SPF，作者发现81%（1084个）可用于评估SPF，整个人群的SPF中位数为5.8%。二倍体肿瘤的SPF中位数（2.6%）显著低于非整倍体肿瘤（10.3%，P小于0.0001）。非整倍体和高SPF均与类固醇受体缺失密切相关。非整倍体肿瘤在高S期值频率方面，相对于受体状态、年龄或绝经状态显示出更显著的差异，而二倍体肿瘤（而非非整倍体肿瘤）在淋巴结阴性患者与淋巴结阳性患者中显示出较低的SPF。由于识别淋巴结阴性患者中的高危少数群体尤为重要，作者单独检查了淋巴结阴性组。在淋巴结阴性组内的每种受体状态、年龄或绝经状态类别中均出现了高SPF亚组，这表明SPF将是一个独立的预后因素。使用此处采用的DNA流式细胞术方法，现在几乎可以为每位乳腺癌患者确定倍性和SPF。这些与已确立的预后因素（如受体状态）相关的因素，现在可以在广泛的患者群体中全面评估其预后意义。
