Kimmig Rainer, Wimberger Pauline, Hillemanns Peter, Kapsner Thomas, Caspari Claudia, Hepp Hermann
Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Munich, D-81377, Germany.
Gynecol Oncol. 2002 Jan;84(1):21-31. doi: 10.1006/gyno.2001.6440.
The outcome of patients with advanced ovarian cancer is poor despite aggressive therapy including surgery and multiagent chemotherapy. Valid prognostic factors are necessary to estimate the course of the disease and to define biologically similar subgroups for analysis of therapeutic efficacy.
This study is the first published prospective study concerning the prognostic significance of DNA-ploidy and S-phase fraction in ovarian cancer following enrichment of tumor cells by cytokeratin labeling. Epithelial cells were labeled by FITC-conjugated cytokeratin antibody (CK 5, 6, 8, and 17) prior to flow cytometric cell cycle analysis in 129 fresh specimens of primary ovarian cancer.
Recurrence-free survival of patients with DNA-diploid primary ovarian cancer was significantly better compared to that of patients with DNA-aneuploid tumors in univariate analysis (47% vs 18%, P = 0.01). The tumor-dependent overall survival of patients with DNA-diploid tumors was 57% compared to 30% with DNA-aneuploid tumors (P = 0.04). In FIGO stage III ovarian cancer DNA-ploidy, optimized by cytokeratin gating for tumor cells, achieved independent prognostic significance. No significance was found for S-phase fraction. However, despite convincing methodological advantages in the detection of DNA-aneuploid subpopulations the clinical significance of cytokeratin gating of epithelial cells was only marginal.
DNA-ploidy has been shown to be as powerful or even more so in comparison to postoperative residual tumor in multivariate analysis for predicting clinical outcome in advanced ovarian cancer. Thus, determination of DNA-ploidy should be introduced to currently recruiting phase III studies for therapy of ovarian cancer for better definition of prognostic subgroups.
尽管采用了包括手术和多药化疗在内的积极治疗，晚期卵巢癌患者的预后仍然很差。需要有效的预后因素来估计疾病进程，并定义生物学上相似的亚组以分析治疗效果。
本研究是首次发表的关于通过细胞角蛋白标记富集肿瘤细胞后，DNA倍体和S期分数在卵巢癌中的预后意义的前瞻性研究。在对129例原发性卵巢癌新鲜标本进行流式细胞术细胞周期分析之前，用异硫氰酸荧光素（FITC）偶联的细胞角蛋白抗体（CK 5、6、8和17）标记上皮细胞。
在单变量分析中，DNA二倍体原发性卵巢癌患者的无复发生存率显著高于DNA非整倍体肿瘤患者（47%对18%，P = 0.01）。DNA二倍体肿瘤患者的肿瘤相关总生存率为57%，而DNA非整倍体肿瘤患者为30%（P = 0.04）。在国际妇产科联盟（FIGO）III期卵巢癌中，通过对肿瘤细胞进行细胞角蛋白门控优化后的DNA倍体具有独立的预后意义。未发现S期分数有显著意义。然而，尽管在检测DNA非整倍体亚群方面具有令人信服的方法学优势，但上皮细胞的细胞角蛋白门控的临床意义仅为边缘性。
在多变量分析中，DNA倍体在预测晚期卵巢癌临床结局方面已被证明与术后残留肿瘤一样强大甚至更强。因此，应将DNA倍体的测定引入目前正在招募的卵巢癌治疗III期研究中，以更好地定义预后亚组。
