Erba E, Giordano M, Danova M, Mazzini G, Ubezio P, Torri V, Mangioni C, Landoni F, Bolis P, Tenti P
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Ann Oncol. 1994 Sep;5(7):627-34. doi: 10.1093/oxfordjournals.annonc.a058935.
Cell kinetics could have prognostic significance in human ovarian cancer and might also help in designing optimal therapy. No data are available on the in vivo kinetics of this tumor using bromodeoxyuridine (BrdU) infusion before surgery.
The kinetic parameters of human ovarian carcinoma were investigated in vivo using BrdU incorporation and bivariate BrdU/DNA flow cytometric (FCM) analysis. Fifty-five previously untreated patients with ovarian cancer (F.I.G.O. clinical stage III and IV) were studied. BrdU (250 mg/sqm) was given i.v. 6 h before surgery and samples of primary tumor and metastasis biopsies were fixed in 70% ethanol. By coupling the BrdU immunoreaction with biparametric FCM analysis, the nuclear DNA content (i.e., ploidy status), the tumor labelling index (LI), the synthesis time (TS) and the potential doubling time of the tumor mass (Tpot) were obtained. BrdU immunodetection was done on histological sections of the same tumors.
The majority of the tumors had a DNA aneuploid content (71.5%). The amount of BrdU-positive S-phase cells varied in different tumor samples and when several samples were taken from the same tumor. The proportion of BrdU-negative S-phase cells was large (50% of the total S phase cells) in almost all cases. The mean LI was 6.1% using FCM and 7.2% on visual count of the slide. The mean TS and Tpot were 14.7 h and 12.5 days, respectively. LI and TS were not correlated with clinical tumor stage, histological grading, residual tumor size or DNA ploidy, but Tpot was significantly higher (p < 0.05) in patients with residual tumor size < 2 cm. Univariate analysis showed that Tpot was significantly associated with the response after first-line chemotherapy (p < 0.009). In multivariate analysis only residual tumor size was related to the response.
Although this in vivo BrdU technique provides information on the kinetic features of human ovarian cancers, it remains questionable whether this information has any additional value compared to currently used prognostic factors which are assessable clinically and surgically.
细胞动力学在人类卵巢癌中可能具有预后意义，也可能有助于设计最佳治疗方案。目前尚无关于术前使用溴脱氧尿苷（BrdU）输注对该肿瘤进行体内动力学研究的数据。
采用BrdU掺入法和双变量BrdU/DNA流式细胞术（FCM）分析，对人类卵巢癌的动力学参数进行体内研究。研究了55例先前未接受治疗的卵巢癌患者（国际妇产科联盟临床分期III期和IV期）。术前6小时静脉注射BrdU（250mg/平方米），将原发性肿瘤和转移灶活检样本固定于70%乙醇中。通过将BrdU免疫反应与双参数FCM分析相结合，获得核DNA含量（即倍体状态）、肿瘤标记指数（LI）、合成时间（TS）和肿瘤块潜在倍增时间（Tpot）。对相同肿瘤的组织切片进行BrdU免疫检测。
大多数肿瘤具有DNA非整倍体含量（71.5%）。不同肿瘤样本以及从同一肿瘤采集的多个样本中，BrdU阳性S期细胞的数量有所不同。几乎在所有病例中，BrdU阴性S期细胞的比例都很大（占S期细胞总数的50%）。采用FCM检测时，平均LI为6.1%，在玻片上目视计数时为7.2%。平均TS和Tpot分别为14.7小时和12.5天。LI和TS与临床肿瘤分期、组织学分级、残留肿瘤大小或DNA倍体无关，但残留肿瘤大小<2cm的患者Tpot显著更高（p<0.05）。单因素分析显示，Tpot与一线化疗后的反应显著相关（p<0.009）。多因素分析表明，只有残留肿瘤大小与反应相关。
尽管这种体内BrdU技术提供了关于人类卵巢癌动力学特征的信息，但与目前临床上和手术中可评估的预后因素相比，该信息是否具有任何附加价值仍值得怀疑。
