Takahashi Y, Takenaka A, Ishiguro T, Noda Y
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Japan.
Cancer. 1994 Jun 15;73(12):3011-4. doi: 10.1002/1097-0142(19940615)73:12<3011::aid-cncr2820731219>3.0.co;2-9.
Flow cytometry (FCM)-measured DNA content may be a predictor in the prognosis of ovarian cancer. Multiple specimens taken from the same ovarian tumor may show a variation in DNA content (i.e., intratumoral DNA heterogeneity). We measured the FCM DNA content of multiple specimens from the same tumor in ovarian cancer, and the relationship among DNA ploidy, intratumoral DNA heterogeneity, retroperitoneal lymph node involvement, and surgical staging was evaluated.
Forty-one patients with primary epithelial ovarian cancer were included in the study. The FCM-measured DNA content of multiple fresh tumor specimens taken from different parts of the same ovarian tumor from each patient was measured. When aneuploidy was observed in at least one specimen from the same tumor, the tumor was defined as an aneuploid tumor. If there were two or more different aneuploid stem lines with a variation of DNA indices (differences of the DNA indices > 0.15) from the same tumor, the presence of intratumoral DNA heterogeneity was defined.
Diploid tumor was found in 8 (19.5%) of the 41 patients, and aneuploid tumor with intratumoral DNA heterogeneity was found in 20 (48.8%). None of the eight patients with diploid tumors demonstrated lymph node involvement. In contrast, lymph node involvement was found in 14 (70.0%) of 20 patients with intratumoral DNA heterogeneity. There was a significant different incidence of lymph node involvement between the groups with and without intratumoral DNA heterogeneity (P < 0.01). The incidence of intratumoral DNA heterogeneity significantly correlated with the International Federation of Gynecology and Obstetrics staging (P < 0.01), while that of aneuploid tumor did not.
Intratumoral DNA heterogeneity reflected a malignant potential for lymph node involvement and its progression in epithelial ovarian cancer.
流式细胞术（FCM）检测的DNA含量可能是卵巢癌预后的一个预测指标。从同一卵巢肿瘤采集的多个样本可能显示出DNA含量的差异（即肿瘤内DNA异质性）。我们检测了卵巢癌同一肿瘤多个样本的FCM DNA含量，并评估了DNA倍体、肿瘤内DNA异质性、腹膜后淋巴结受累及手术分期之间的关系。
本研究纳入41例原发性上皮性卵巢癌患者。测量了从每位患者同一卵巢肿瘤不同部位采集的多个新鲜肿瘤样本的FCM检测DNA含量。当在同一肿瘤的至少一个样本中观察到非整倍体时，该肿瘤被定义为非整倍体肿瘤。如果同一肿瘤存在两个或更多不同的非整倍体干细胞系且DNA指数有差异（DNA指数差异>0.15），则定义为存在肿瘤内DNA异质性。
41例患者中8例（19.5%）为二倍体肿瘤，20例（48.8%）为具有肿瘤内DNA异质性的非整倍体肿瘤。8例二倍体肿瘤患者均未出现淋巴结受累。相比之下，20例具有肿瘤内DNA异质性的患者中有14例（70.0%）出现淋巴结受累。有和没有肿瘤内DNA异质性的两组之间淋巴结受累的发生率有显著差异（P<0.01）。肿瘤内DNA异质性的发生率与国际妇产科联盟分期显著相关（P<0.01），而非整倍体肿瘤的发生率则不然。
肿瘤内DNA异质性反映了上皮性卵巢癌淋巴结受累及其进展的恶性潜能。
