Meyer J S, Koehm S L, Hughes J M, Higa E, Wittliff J L, Lagos J A, Manes J L
St. Luke's Hospital, Chesterfield, MO 63017.
Cancer. 1993 Jun 1;71(11):3531-40. doi: 10.1002/1097-0142(19930601)71:11<3531::aid-cncr2820711112>3.0.co;2-0.
The S-phase fraction relates to proliferation, an important determinant of tumor behavior, and has been measured most accurately with the DNA precursor tritiated thymidine (TT). The TT labeling index (LI) is a strong stage-independent prognostic indicator for breast carcinoma. The thymidine analogue 5-bromodeoxyuridine (BrdU) is also incorporated into DNA and has the advantage over TT of immunohistochemical detectability rather than requiring autoradiography, but it is less well studied in breast carcinoma. This report demonstrates the equivalence of TT and BrdU LI and explores the relationships between LI and other biologic measurements.
The LI of 234 consecutive breast carcinomas were measured with TT as was a subsequent series of 450 cases with BrdU, both by incubation in vitro.
The mean BrdU LI was 6.4 +/- 0.3% in comparison with 6.9 +/- 0.4% in the prior TT series. LI was unaffected by storage for 24 hours at 4 degrees C before labeling with BrdU. The BrdU and TT LI both correlated: (1) positively with tumor size, histologic type, nuclear size, the number of axillary metastases, the level of DNA ploidy, and the percent S-phase by flow cytometry and (2) negatively with the age of the patient and the levels of estrogen receptor and progesterone receptor measured either by ligand binding or by immunohistochemistry.
BrdU labeling in vitro was an advantageous method for measuring S-phase fraction in breast carcinoma that produced results comparable to those from TT labeling. It should be equally effective for breast cancer kinetic classification and prognosis and is a suitable standard to evaluate newer methods for measuring cellular proliferation.
S期分数与增殖相关，增殖是肿瘤行为的一个重要决定因素，使用DNA前体氚标记胸腺嘧啶核苷（TT）能最准确地进行测量。TT标记指数（LI）是乳腺癌一个强大的与分期无关的预后指标。胸腺嘧啶类似物5-溴脱氧尿苷（BrdU）也能掺入DNA，并且相对于TT具有免疫组织化学可检测性的优势，无需放射自显影，但在乳腺癌中的研究较少。本报告证明了TT和BrdU LI的等效性，并探讨了LI与其他生物学测量指标之间的关系。
通过体外孵育，对234例连续乳腺癌患者测量TT LI，并对随后的450例患者测量BrdU LI。
平均BrdU LI为6.4±0.3%，而之前TT系列为6.9±0.4%。在用BrdU标记前，在4℃下储存24小时不影响LI。BrdU和TT LI均与以下指标相关：（1）与肿瘤大小、组织学类型、核大小、腋窝转移数量、DNA倍体水平以及流式细胞术检测的S期百分比呈正相关；（2）与患者年龄以及通过配体结合或免疫组织化学测量的雌激素受体和孕激素受体水平呈负相关。
体外BrdU标记是测量乳腺癌S期分数的一种有利方法，其结果与TT标记相当。它对于乳腺癌动力学分类和预后应同样有效，并且是评估测量细胞增殖新方法的合适标准。
