Gregorcyk S, Kang Y, Brandt D, Kolm P, Singer G, Perry R R
Department of General Surgery, Eastern Virginia Medical School, Norfolk, USA.
Ann Surg Oncol. 1996 Jan;3(1):8-14. doi: 10.1007/BF02409045.
Many new prognostic factors for breast cancer have been described, and yet the ability to predict patient outcomes remains poor. Overexpression of p-glycoprotein (p-gp), the multidrug resistance efflux pump, confers a worse prognosis to patients with certain leukemias and other tumors. The purpose of this study was to analyze the potential usefulness of p-gp expression as a prognostic factor in patients with breast cancer.
Paraffin blocks were obtained from 55 previously untreated patients who underwent surgery between 1987 and 1988. To determine p-gp expression, tumor cell suspensions were incubated with the p-gp-specific C219 monoclonal antibody and analyzed using an indirect immunofluorescent flow cytometric assay.
Twenty-four (44%) of the tumors were p-gp positive and 31 (56%) were p-gp negative. Among the p-gp positive patients, 65% had recurrence of their disease, whereas only 13% of the p-gp negative patients experienced recurrence (p = 0.0001). The 5-year disease-free rate for p-gp positive patients was 39% compared with 83% for p-gp negative patients (p = 0.0001). In univariate analysis examining 10 different variables, significant predictors of recurrence were p-gp, stage, and tumor size. Multivariate analysis using Cox Proportional Hazards regression showed that only p-gp and stage were significant independent predictors of recurrence (p = 0.0002).
p-gp is frequently expressed in patients with untreated breast cancer, with p-gp-positive patients being at significantly greater risk for disease recurrence. p-gp appears to be a useful prognostic factor in breast cancer and could potentially help guide management.
已描述了许多乳腺癌新的预后因素,但预测患者预后的能力仍然较差。多药耐药外排泵P糖蛋白(p-gp)的过表达使某些白血病和其他肿瘤患者的预后更差。本研究的目的是分析p-gp表达作为乳腺癌患者预后因素的潜在实用性。
从1987年至1988年间接受手术的55例未经治疗的患者中获取石蜡块。为了确定p-gp表达,将肿瘤细胞悬液与p-gp特异性C219单克隆抗体孵育,并使用间接免疫荧光流式细胞术进行分析。
24例(44%)肿瘤为p-gp阳性,31例(56%)为p-gp阴性。在p-gp阳性患者中,65%出现疾病复发,而p-gp阴性患者中只有13%出现复发(p = 0.0001)。p-gp阳性患者的5年无病生存率为39%,而p-gp阴性患者为83%(p = 0.0001)。在检查10个不同变量的单因素分析中,复发的显著预测因素是p-gp、分期和肿瘤大小。使用Cox比例风险回归的多因素分析表明,只有p-gp和分期是复发的显著独立预测因素(p = 0.0002)。
p-gp在未经治疗的乳腺癌患者中经常表达,p-gp阳性患者疾病复发风险显著更高。p-gp似乎是乳腺癌一个有用的预后因素,可能有助于指导治疗。