Meyer J S, McDivitt R W, Stone K R, Prey M U, Bauer W C
Breast Cancer Res Treat. 1984;4(2):79-88. doi: 10.1007/BF01806389.
The S-phase fraction (SP) measured by flow cytometry of DNA and the thymidine labeling index (TLI) measured autoradiographically indicate the proportion of carcinoma cells currently synthesizing DNA and reflect the rate of proliferation. The TLI and SPF are lognormally distributed. The median TLI performed to maximize precursor uptake is near 5% (5 labeled carcinoma cells per 100) the mean near 7%, and the range from less than 1% to near 40%. Corresponding values for the SPF measured by DNA flow cytometry are slightly higher when appropriate measures are taken to reduce background debris counts and other artefacts. Residual elevation of SPF above TLI may result from S-phase arrested cells. Flow cytometric histograms show that clearly aneuploid cell lines exist in 50-80% of primary breast carcinomas. Aneuploid breast carcinomas have higher mean TLI than diploid breast carcinomas, and therefore proliferate more rapidly. They also more frequently lack estrogen receptor (ER). Carcinomas with minimal nuclear anaplasia, particularly those of tubular, mucinous, infiltrating lobular and adenocystic types have low TLI and SPF, whereas carcinomas with highly anaplastic nuclei, including medullary carcinomas, have high TLI and SPF. TLI and SPF correlate inversely with ER and PgR content, have no relationship to axillary lymph nodal status, and have a weak positive correlation with tumor size and a weak negative correlation with age. High TLI predicts a high risk of early relapse after primary therapy for both node-negative and node-positive carcinomas. Carcinomas that produce brain metastases have particularly high TLI. Current evidence suggests that high SPF and aneuploidy may prove to have prognostic significance like TLI.
通过DNA流式细胞术测量的S期分数（SP）和通过放射自显影术测量的胸苷标记指数（TLI）表明当前正在合成DNA的癌细胞比例，并反映增殖速率。TLI和SPF呈对数正态分布。为使前体摄取最大化而进行的TLI中位数接近5%（每100个中有5个标记的癌细胞），平均值接近7%，范围从小于1%到接近40%。当采取适当措施减少背景碎片计数和其他假象时，通过DNA流式细胞术测量的SPF相应值略高。SPF高于TLI的残余升高可能源于S期停滞细胞。流式细胞术直方图清楚地显示，50 - 80%的原发性乳腺癌中存在明显的非整倍体细胞系。非整倍体乳腺癌的平均TLI高于二倍体乳腺癌，因此增殖更快。它们也更频繁地缺乏雌激素受体（ER）。核间变最小的癌，特别是管状、黏液性、浸润性小叶和腺囊性类型的癌，TLI和SPF较低，而核高度间变的癌，包括髓样癌，TLI和SPF较高。TLI和SPF与ER和PgR含量呈负相关，与腋窝淋巴结状态无关，与肿瘤大小呈弱正相关，与年龄呈弱负相关。高TLI预测原发性治疗后无论是淋巴结阴性还是阳性的癌早期复发风险都高。发生脑转移的癌TLI特别高。目前的证据表明，高SPF和非整倍体可能与TLI一样具有预后意义。
