Lukes A S, Kohler M F, Pieper C F, Kerns B J, Bentley R, Rodriguez G C, Soper J T, Clarke-Pearson D L, Bast R C, Berchuck A
Department of Obstetrics and Gynecology/Division of Gynecologic Oncology, Duke Comprehensive Cancer Center, Durham, North Carolina.
Cancer. 1994 May 1;73(9):2380-5. doi: 10.1002/1097-0142(19940501)73:9<2380::aid-cncr2820730922>3.0.co;2-g.
Several molecular-genetic alterations in endometrial cancers, including aneuploidy and aberrant expression of p53 and HER-2/neu, have been associated with poor prognosis. To determine the importance of molecular-genetic factors relative to more traditional surgical-pathologic prognostic factors, a multivariable analysis was performed.
Immunohistochemical staining for p53, HER-2/neu, estrogen receptor, progesterone receptor, and epidermal growth factor receptor was performed on frozen sections from 100 primary endometrial cancers. DNA ploidy was determined using computerized image analysis of Feulgen-stained touch preparations. In addition, information regarding surgical-pathologic features of the cancers was obtained. Univariable analysis was performed followed by multivariable analysis using Cox's proportional hazards model to identify variables predictive of poor prognosis.
With univariable analysis, race, histologic type, stage, grade, myometrial invasion, estrogen receptor, progesterone receptor, ploidy, p53 and HER-2/neu were predictive of the presence of persistent or recurrent disease. In the multivariable analysis, only International Federation of Gynecology and Obstetrics stage (P = 0.005), grade (P = 0.005), myometrial invasion (P = 0.024), and ploidy (P = 0.028) were significant.
Among molecular-genetic prognostic factors, DNA ploidy was the most strongly predictive of persistent or recurrent disease.
子宫内膜癌的几种分子遗传学改变,包括非整倍体以及p53和HER-2/neu的异常表达,均与预后不良相关。为了确定分子遗传学因素相对于更传统的手术病理预后因素的重要性,进行了多变量分析。
对100例原发性子宫内膜癌的冰冻切片进行p53、HER-2/neu、雌激素受体、孕激素受体和表皮生长因子受体的免疫组织化学染色。使用对福尔根染色的触摸涂片进行计算机图像分析来确定DNA倍体。此外,获取了有关癌症手术病理特征的信息。先进行单变量分析,然后使用Cox比例风险模型进行多变量分析,以识别预测预后不良的变量。
单变量分析显示,种族、组织学类型、分期、分级、肌层浸润、雌激素受体、孕激素受体、倍体、p53和HER-2/neu可预测持续性或复发性疾病的存在。多变量分析中,只有国际妇产科联盟分期(P = 0.005)、分级(P = 0.005)、肌层浸润(P = 0.024)和倍体(P = 0.028)具有显著性。
在分子遗传学预后因素中,DNA倍体对持续性或复发性疾病的预测性最强。