Nakayama Satoru, Nakayama Kentaro, Takebayashi Yuji, Hata Kohkichi, Fujiwaki Ritsuto, Fukumoto Manabu, Miyazaki Kohji
Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, Japan.
Int J Mol Med. 2003 May;11(5):621-5.
We analyzed a series of ovarian carcinomas from patients treated with cisplatin-based chemotherapy for loss of heterozygosity (LOH) to determine the relationship between microsatellite alteration and prognosis. Patients with tumors that had lost alleles at loci 3p14-21, 12qter, or 17p13.3 showed significantly reduced survival compared to patients with tumors that retained both alleles at those loci. The 5-year mortality rates for patients exhibiting allele loss and patients with allele retention were 50 and 41%, respectively, for the 3p14-21 locus (P=0.0023); 57 and 24%, respectively, for 12qter (P=0.0256); and 55 and 40%, respectively, for 17p13.3 (P=0.0489). A statistically significant difference was also observed with respect to fractional allelic loss (FAL), which was a significant indicator for disease recurrence (P=0.0227). The prognosis of patients with high FAL values were significantly worse compared to those with low FAL values (P=0.0306). Our results suggested that LOH at loci 3p14-21, 12qter, or 17p13.3 was a significant predictor of poor survival in ovarian carcinomas treated with cisplatin-based chemotherapy. Furthermore, the association of FAL value with therapy response indicated that ovarian carcinomas with high levels of chromosomal alteration may be more resistant to this type of chemotherapy.
我们分析了一系列接受以顺铂为基础的化疗的卵巢癌患者的杂合性缺失(LOH)情况,以确定微卫星改变与预后之间的关系。与在3p14 - 21、12qter或17p13.3位点保留两个等位基因的肿瘤患者相比,在这些位点丢失等位基因的肿瘤患者生存率显著降低。在3p14 - 21位点,等位基因丢失患者和等位基因保留患者的5年死亡率分别为50%和41%(P = 0.0023);在12qter位点分别为57%和24%(P = 0.0256);在17p13.3位点分别为55%和40%(P = 0.0489)。在等位基因分数丢失(FAL)方面也观察到了统计学上的显著差异,FAL是疾病复发的一个重要指标(P = 0.0227)。FAL值高的患者预后明显比FAL值低的患者差(P = 0.0306)。我们的结果表明,在3p14 - 21、12qter或17p13.3位点的LOH是接受以顺铂为基础的化疗的卵巢癌患者生存不良的一个重要预测指标。此外,FAL值与治疗反应的关联表明,染色体改变水平高的卵巢癌可能对这种化疗更具抗性。