Nakayama K, Takebayashi Y, Hata K, Fujiwaki R, Iida K, Fukumoto M, Miyazaki K
Department of Obstetrics and Gynecology, Shimane Medical University, Enyacho 89-1, Izumo 693-8501, Japan.
Br J Cancer. 2004 Mar 22;90(6):1204-10. doi: 10.1038/sj.bjc.6601681.
Ovarian tumours of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas. These tumours are often associated with a significantly better prognosis than ovarian carcinomas. However, a subset of these tumours can progress and become lethal. In order to seek sensitive diagnostic tools for monitoring patients after surgical operation, we performed a genome-wide scan for loss of heterozygosity (LOH) in 41 mucinous LMPs using 91 polymorphic microsatellite markers at an average interval of 50 cM across all of the human chromosomes and 25 LOH markers reportedly associated with ovarian carcinoma. In addition, we assessed whether clinicopathological parameters, microvessel density, Ki-67 labeling index, apoptotic index or p53 overexpression would be useful for predicting the postoperative outcome of LMP patients. Of the 116 markers examined, 19q12 and Xq11-12 showed significant correlation between postoperative progression-free survival time and LOH status (P<0.05). Patients with a high Ki-67 labeling index had a significantly poorer progression-free survival time than those with lower levels (P=0.042). Other clinicopathological factors and immunohistochemical analysis had no correlation with progression-free survival time in this series of patients. When the combination of LOH at 19q12 and/or Xq11-12 was assessed using Cox's regression analysis, patients with tumours that showed LOH at these positions were at greatest risk of progression (P=0.0073). These findings suggest that the identification of LOH at 19q12 and/or Xq11-12 in former mucinous LMP sites should alert the clinician to the presence of a potentially aggressive lesion in the coelomic epithelium, even if a distinction between second primary tumours or recurrence could not be determined.
低恶性潜能(LMP)卵巢肿瘤介于腺瘤和卵巢癌之间。这些肿瘤的预后通常比卵巢癌好得多。然而,其中一部分肿瘤可能会进展并导致死亡。为了寻找用于术后监测患者的敏感诊断工具,我们使用91个多态性微卫星标记对41例黏液性LMP进行了全基因组杂合性缺失(LOH)扫描,这些标记在所有人类染色体上平均间隔50 cM,另外还有25个据报道与卵巢癌相关的LOH标记。此外,我们评估了临床病理参数、微血管密度、Ki-67标记指数、凋亡指数或p53过表达是否有助于预测LMP患者的术后结局。在所检测的116个标记中,19q12和Xq11-12显示术后无进展生存时间与LOH状态之间存在显著相关性(P<0.05)。Ki-67标记指数高的患者无进展生存时间明显短于水平较低的患者(P=0.042)。在这组患者中,其他临床病理因素和免疫组化分析与无进展生存时间无关。当使用Cox回归分析评估19q12和/或Xq11-12处LOH的组合时,在这些位置显示LOH的肿瘤患者进展风险最大(P=0.0073)。这些发现表明,在前黏液性LMP部位鉴定出19q12和/或Xq11-12处的LOH应提醒临床医生,即使无法确定是第二原发性肿瘤还是复发,体腔上皮中也可能存在潜在侵袭性病变。