对204例接受铂类方案治疗的卵巢癌进行P21WAF1、P27KIP1、TP53和C-MYC分析。

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

作者信息

Plisiecka-Hałasa J, Karpińska G, Szymańska T, Ziółkowska I, Madry R, Timorek A, Debniak J, Ułańska M, Jedryka M, Chudecka-Głaz A, Klimek M, Rembiszewska A, Kraszewska E, Dybowski B, Markowska J, Emerich J, Płuzańska A, Goluda M, Rzepka-Górska I, Urbański K, Zieliński J, Stelmachów J, Chrabowska M, Kupryjańczyk J

机构信息

Department of Molecular Pathology, Institute of Oncology, Roentgena, Warsaw, Poland.

出版信息

Ann Oncol. 2003 Jul;14(7):1078-85. doi: 10.1093/annonc/mdg299.

DOI:10.1093/annonc/mdg299

PMID:12853350

Abstract

BACKGROUND

The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients.

MATERIALS AND METHODS

Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups.

RESULTS

High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001).

CONCLUSIONS

We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.

摘要

背景

细胞周期调节蛋白在卵巢癌中的预后及预测价值尚未明确。我们评估了P21（WAF1）、P27（KIP1）、C-MYC、TP53和Ki67表达在卵巢癌患者中的临床及生物学意义。

材料与方法

对204例接受铂类化疗的国际妇产科联盟（FIGO）IIB至IV期卵巢癌进行免疫组化分析。在整个研究组以及TP53阴性和TP53阳性亚组中，采用Cox模型和逻辑回归模型进行多因素分析。

结果

高P21（WAF1）标记指数（LI）是铂类敏感反应的独立阳性预测指标（P = 0.02）。仅在TP53阴性组中，P21（WAF1）LI（P = 0.02）或P21（WAF1）加P27（KIP1）LI（P = 0.004）对总生存期有正向影响。Ki67 LI与无病生存期呈临界相关性（P = 0.05）。在TP53阴性组中，生长分数与P21（WAF1）和P27（KIP1）指数呈负相关（分别为P = 0.023和0.008），而在TP53阳性组中，这些相关性为临界相关或不存在。子宫内膜样癌和透明细胞癌与其他类型的癌不同，其TP53积累发生率低、C-MYC过表达发生率高（70%）且Ki67 LI中位数低（所有P均<0.001）。