Weidner N, Moore D H, Ljung B M, Waldman F M, Goodson W H, Mayall B, Chew K, Smith H S
Department of Pathology, University of California, San Francisco 94143-0102.
Am J Surg Pathol. 1993 Oct;17(10):987-94. doi: 10.1097/00000478-199310000-00003.
Tumor proliferation is inversely associated with survival in patients with breast carcinoma. Labeling of tumor cells with bromodeoxyuridine (BRDU) correlates highly with that seen with [3H]thymidine, the current "gold standard" for measuring tumor S-phase. However, the relationship of BRDU labeling to mitotic figure content and tumor grade remains incompletely defined. To determine this, we labeled 55 breast carcinomas with BRDU in vivo and correlated the results with mitotic figure content. The BRDU labeling index was the number of BRDU-positive cells/2,000 tumor cells, the mitotic figure index was the number of mitotic figures per 1,000 tumor cells, and the mitotic figure count was the number of mitotic figures per 10 high-powered fields. BRDU labeling was also correlated with tumor grade (Scarff-Bloom-Richardson). The BRDU labeling index correlated highly with the mitotic figure index (r = 0.814, p = 7.0 x 10(-14)), mitotic figure count (r = 0.725, p = 6.0 x 10(-10)), and tumor grade (r = 0.68, p = 1.1 x 10(-8)). The correlation of BRDU labeling with mitotic figure content was strong enough to suggest that a very carefully measured mitotic figure index provides an estimate of tumor growth fraction equivalent to the BRDU labeling index. Also, analysis of variance showed that the mitotic figure index was twice as precise as the mitotic figure count in estimating BRDU labeling, and thus was a more accurate measure of tumor proliferation. Moreover, measurements made by the mitotic figure index were as precise as those made by BRDU labeling. However, which method is optimal for estimating tumor proliferation rate remains unclear. Further studies are indicated.
肿瘤增殖与乳腺癌患者的生存率呈负相关。用溴脱氧尿苷（BRDU）标记肿瘤细胞与用[3H]胸腺嘧啶核苷标记的结果高度相关，[3H]胸腺嘧啶核苷是目前测量肿瘤S期的“金标准”。然而，BRDU标记与有丝分裂象含量和肿瘤分级之间的关系仍未完全明确。为了确定这一点，我们在体内用BRDU标记了55例乳腺癌，并将结果与有丝分裂象含量进行了关联。BRDU标记指数是BRDU阳性细胞数/2000个肿瘤细胞，有丝分裂象指数是每1000个肿瘤细胞中的有丝分裂象数，有丝分裂象计数是每10个高倍视野中的有丝分裂象数。BRDU标记也与肿瘤分级（斯卡夫-布卢姆-理查森分级）相关。BRDU标记指数与有丝分裂象指数（r = 0.814，p = 7.0×10-14）、有丝分裂象计数（r = 0.725，p = 6.0×10-10）和肿瘤分级（r = 0.68，p = 1.1×10-8）高度相关。BRDU标记与有丝分裂象含量的相关性足够强，表明非常仔细测量的有丝分裂象指数提供了与BRDU标记指数相当的肿瘤生长分数估计值。此外，方差分析表明，在估计BRDU标记方面，有丝分裂象指数比有丝分裂象计数精确两倍，因此是肿瘤增殖的更准确测量指标。而且，用有丝分裂象指数进行的测量与用BRDU标记进行的测量一样精确。然而，哪种方法最适合估计肿瘤增殖率仍不清楚。需要进一步研究。
