Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
Mod Pathol. 2011 Sep;24(9):1262-71. doi: 10.1038/modpathol.2011.75. Epub 2011 May 6.
The prognostic value of molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in endometrial cancer is conflicting, possibly due to the fact that different studies have used mixtures of histotypes, FIGO stages and different non-standardized non-automated methods. We have evaluated the prognostic value of classical prognostic factors, molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in a population-based cohort of FIGO stage I endometrial endometrioid adenocarcinomas. Curettings of 224 FIGO stage I endometrial endometrioid adenocarcinoma patients were reviewed. Clinical information, including follow-up, was obtained from the patients' charts. Microsatellite instability and morphometric mean shortest nuclear axis were obtained in whole tissue sections and molecular biomarkers using tissue microarrays. DNA ploidy was analyzed by image cytometry. Univariate (Kaplan-Meier method) and multivariate (Cox model) survival analysis was performed. With median follow-up of 66 months (1-209), 14 (6%) patients developed metastases. Age, microsatellite instability, molecular biomarkers (p16, p21, p27, p53 and survivin) and morphometric mean shortest nuclear axis had prognostic value. With multivariate analysis, combined survivin, p21 and microsatellite instability overshadowed all other variables. Patients in which any of these features had favorable values had an excellent prognosis, in contrast to those with either high survivin or low p21 (97 vs 78% survival, P<0.0001, hazard ratio=7.8). Combined high survivin and low p21 values and microsatellite instability high identified a small subgroup with an especially poor prognosis (survival rate 57%, P=0.01, hazard ratio=5.6). We conclude that low p21 and high survivin expression are poor prognosis indicators in FIGO stage I endometrial endometrioid adenocarcinoma, especially when high microsatellite instability occurs.
在子宫内膜样腺癌中，分子生物标志物、微卫星不稳定性、DNA 倍性和形态学平均最短核轴的预后价值存在争议，这可能是由于不同的研究使用了不同的组织学类型、FIGO 分期和不同的非标准化非自动化方法的混合物。我们评估了经典预后因素、分子生物标志物、微卫星不稳定性、DNA 倍性和形态学平均最短核轴在基于人群的 FIGO 分期 I 子宫内膜样腺癌患者中的预后价值。对 224 例 FIGO 分期 I 子宫内膜样腺癌患者的刮宫标本进行了回顾性分析。临床信息，包括随访情况，从患者的病历中获得。在全组织切片中获得微卫星不稳定性和形态学平均最短核轴，并使用组织微阵列获得分子生物标志物。使用图像细胞仪分析 DNA 倍性。进行了单因素（Kaplan-Meier 法）和多因素（Cox 模型）生存分析。中位随访时间为 66 个月（1-209），14 例（6%）患者发生转移。年龄、微卫星不稳定性、分子生物标志物（p16、p21、p27、p53 和 survivin）和形态学平均最短核轴具有预后价值。多因素分析显示，联合 survivin、p21 和微卫星不稳定性掩盖了所有其他变量。具有这些特征中的任何一个有利值的患者预后良好，而那些具有高 survivin 或低 p21 的患者则相反（97%与 78%的生存率，P<0.0001，风险比=7.8）。高 survivin 和低 p21 值和微卫星不稳定性高的联合值确定了一个预后特别差的小亚组（生存率为 57%，P=0.01，风险比=5.6）。我们的结论是，低 p21 和高 survivin 表达是 FIGO 分期 I 子宫内膜样腺癌的不良预后指标，尤其是在高微卫星不稳定性发生时。
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