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低风险子宫内膜癌:基于肿瘤倍体的治疗策略评估及其他预后指标的识别

Low-risk endometrial carcinoma: assessment of a treatment policy based on tumor ploidy and identification of additional prognostic indicators.

作者信息

Lim P, Aquino-Parsons C F, Wong F, Dupuis B, Phillips D, Zhou C, Gilks C B

机构信息

Department of Radiation Oncology, British Columbia Cancer Agency and Vancouver Hospital, Vancouver, British Columbia, V5Z 4E6, Canada.

出版信息

Gynecol Oncol. 1999 May;73(2):191-5. doi: 10.1006/gyno.1999.5365.

DOI:10.1006/gyno.1999.5365
PMID:10329033
Abstract

OBJECTIVES

The aims of this study were (1) to assess a treatment policy for patients with low-risk endometrioid endometrial carcinoma where adjuvant treatment decisions have been based on ploidy status of the tumor, and (2) to screen diploid, low-risk tumors for additional features of prognostic significance.

METHODS

Between 01/1992 and 08/1996, 406 patients were referred to the B.C. Cancer Agency-Vancouver Clinic with typical endometrial adenocarcinomas limited to <50% myometrial invasion and no vascular space invasion or grade 3 disease on pathology review ("low-risk stage I endometrial carcinoma"). Patients were prospectively assigned to treatment groups based on tumor ploidy. Those patients with aneuploid tumors (n = 91) were treated with adjuvant vaginal vault radiotherapy while those with diploid tumors (n = 315) were followed and treated only at relapse. The hysterectomy specimens from all 14 patients in the untreated, diploid group who relapsed, as well as 28 stage- and grade-matched diploid controls who did not fail, were analyzed by immunohistochemical staining for estrogen receptor (ER), Bcl-2, and p53 proteins.

RESULTS

There were no significant differences in the stage (Ia vs Ib) and grade (G1 vs G2) distribution for the diploid and aneuploid groups. Overall median age was 64 years (range 27-90 years) and was also not significantly different for the two groups. The median follow-up for the entire cohort is 45 months (range 1-76 months). There have been 14 failures in the diploid group and 4 failures in the aneuploid group with actuarial 5-year disease-free survival rates of 95.0 and 95.2%, respectively (P = NS). Eight of the failures in the diploid group occurred at the vaginal vault and were all subsequently salvaged with radiotherapy. All but 1 of the failures in the aneuploid group were considered incurable. Of the 14 diploid tumors from patients who failed, 7 stained positively for p53, compared to 4 of 28 diploid controls (P = 0.02). No significant differences were seen in the diploid tumors that recurred, compared to controls, with respect to Bcl-2 or ER expression.

CONCLUSIONS

Patients with diploid, low-risk stage I endometrial cancers have excellent prospects for relapse-free and overall survival. Patients with aneuploid tumors treated with adjuvant radiotherapy have the same risk of relapse as untreated patients with diploid tumors; however, their ultimate survival may be lower as a smaller proportion of aneuploid failures are salvageable. While p53 expression in diploid tumors is associated with increased risk of relapse, Bcl-2 and ER are not useful prognostic indicators in this setting.

摘要

目的

本研究的目的是:(1)评估一项针对低风险子宫内膜样腺癌患者的治疗策略,该策略中辅助治疗决策基于肿瘤的倍体状态;(2)筛查二倍体低风险肿瘤以寻找其他具有预后意义的特征。

方法

在1992年1月至1996年8月期间,406例被诊断为典型子宫内膜腺癌的患者被转诊至不列颠哥伦比亚癌症机构 - 温哥华诊所,这些肿瘤局限于肌层浸润<50%,病理检查无脉管间隙浸润或3级病变(“低风险I期子宫内膜癌”)。患者根据肿瘤倍体被前瞻性地分配到治疗组。那些非整倍体肿瘤患者(n = 91)接受辅助阴道穹窿放疗,而二倍体肿瘤患者(n = 315)进行随访,仅在复发时进行治疗。对未接受治疗的二倍体组中复发的14例患者以及28例未复发的分期和分级匹配的二倍体对照患者的子宫切除标本进行雌激素受体(ER)、Bcl-2和p53蛋白的免疫组化染色分析。

结果

二倍体组和非整倍体组在分期(Ia vs Ib)和分级(G1 vs G2)分布上无显著差异。总体中位年龄为64岁(范围27 - 90岁),两组之间也无显著差异。整个队列的中位随访时间为45个月(范围1 - 76个月)。二倍体组有14例复发,非整倍体组有4例复发,精算5年无病生存率分别为95.0%和95.2%(P = 无统计学意义)。二倍体组的8例复发发生在阴道穹窿,随后均通过放疗挽救。非整倍体组除1例复发外,其余均被认为无法治愈。在复发患者的14例二倍体肿瘤中,7例p53染色呈阳性,而28例二倍体对照中有4例阳性(P = 0.02)。与对照相比,复发的二倍体肿瘤在Bcl-2或ER表达方面无显著差异。

结论

二倍体低风险I期子宫内膜癌患者具有良好的无复发生存和总生存前景。接受辅助放疗的非整倍体肿瘤患者与未接受治疗的二倍体肿瘤患者复发风险相同;然而,他们的最终生存率可能较低,因为非整倍体复发患者中可挽救的比例较小。虽然二倍体肿瘤中p53表达与复发风险增加相关,但在这种情况下Bcl-2和ER不是有用的预后指标。

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