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晚期非小细胞肺癌中胎盘同工型谷胱甘肽S-转移酶和P-糖蛋白的表达:与治疗反应和生存的关联

Placental isoform glutathione S-transferase and P-glycoprotein expression in advanced nonsmall cell lung cancer: association with response to treatment and survival.

作者信息

Vlachogeorgos George S, Manali Effrosini D, Blana Ekaterini, Legaki Stella, Karagiannidis Napoleon, Polychronopoulos Vlassios S, Roussos Charis

机构信息

Department of Pulmonary Diseases, General Hospital of Chalkis, Greece.

出版信息

Cancer. 2008 Dec 25;114(6):519-26. doi: 10.1002/cncr.23981.

DOI:10.1002/cncr.23981
PMID:19006072
Abstract

BACKGROUND

Increased expression of the glutathione S-transferase placental isoform (GST-pi) and of P-glycoprotein (P-gp) in tissues from patients with nonsmall cell lung cancer (NSCLC) has been associated with poor antineoplastic drug sensitivity, response to treatment, and survival. However, the diagnosis of advanced NSCLC often is based on cytology. The objectives of the current study were to examine GST-pi and P-gp expression in cytologic specimens from patients with unresectable NSCLC and to determine the association of that expression with response to chemotherapy and survival.

METHODS

Patients with unresectable, cytologically diagnosed NSCLC were eligible for the study. Diagnosis was made by fiberoptic bronchoscopy, and staging was done according to international standards. All patients received sequential chemoradiotherapy and were re-evaluated for treatment response. GST-pi and P-gp expression levels were evaluated by immunocytochemistry and immunohistochemistry of bronchial brushing/washing and bronchial tissue biopsy, respectively. Survival was defined as the time between diagnosis and death or last follow-up at 24 months.

RESULTS

Thirty-nine patients were included in the study. There were 35 men and 4 women, and the mean patient age (+/-standard deviation was 61.4 years (+/-9.1 years). There were 4 patients with stage IIIA NSCLC, 32 patients with stage IIIB NSCLC, and 3 patients with stage IV NSCLC. Cytologic evaluation of GST-pi and P-gp expression paralleled expression determined in pathology specimens. GST-pi and P-gp expression levels were associated inversely with response to chemotherapy and survival.

CONCLUSIONS

Cytologic evaluation of GST-pi and P-gp expression may predictor the response to treatment and the survival of patients with advanced NSCLC.

摘要

背景

非小细胞肺癌(NSCLC)患者组织中谷胱甘肽S-转移酶胎盘同工酶(GST-pi)和P-糖蛋白(P-gp)表达增加与抗肿瘤药物敏感性差、治疗反应及生存率相关。然而,晚期NSCLC的诊断通常基于细胞学检查。本研究的目的是检测不可切除NSCLC患者细胞学标本中GST-pi和P-gp的表达,并确定该表达与化疗反应及生存率的关系。

方法

符合条件的研究对象为经细胞学诊断为不可切除NSCLC的患者。通过纤维支气管镜进行诊断,并根据国际标准进行分期。所有患者均接受序贯放化疗,并重新评估治疗反应。分别通过支气管刷检/冲洗物及支气管组织活检的免疫细胞化学和免疫组织化学评估GST-pi和P-gp的表达水平。生存期定义为诊断至死亡或24个月最后一次随访的时间。

结果

39例患者纳入本研究。其中男性35例,女性4例,患者平均年龄(±标准差)为61.4岁(±9.1岁)。ⅢA期NSCLC患者4例,ⅢB期NSCLC患者32例,Ⅳ期NSCLC患者3例。GST-pi和P-gp表达的细胞学评估与病理标本中的表达情况相似。GST-pi和P-gp表达水平与化疗反应及生存率呈负相关。

结论

GST-pi和P-gp表达的细胞学评估可能预测晚期NSCLC患者的治疗反应及生存期。

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