QUANTITATIVE IMMUNOCYTOCHEMICAL ASSAYS OF P-GLYCOPROTEIN IN BREAST CARCINOMAS - CORRELATION TO MESSENGER-RNA EXPRESSION AND TO IMMUNOHISTOCHEMICAL PROGNOSTIC INDICATORS
QUANTITATIVE IMMUNOCYTOCHEMICAL ASSAYS OF P-GLYCOPROTEIN IN BREAST CARCINOMAS - CORRELATION TO MESSENGER-RNA EXPRESSION AND TO IMMUNOHISTOCHEMICAL PROGNOSTIC INDICATORS
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DOI：
10.1093/jnci/86.20.1539
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发表时间：
1994-10-19
影响因子：
10.3
通讯作者：
PIANA, L
中科院分区：
文献类型：
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作者：
CHARPIN, C;VIELH, P;PIANA, L
背景：由于细胞耐药导致的化疗失败仍然是大多数癌症患者的主要问题。一种已被表征的耐药类型是多药耐药现象，这表明由于具有广泛底物特异性的能量依赖性单向药物外排泵的作用，癌细胞积累药物的能力降低。该药物泵由170 kd的跨膜糖蛋白p -糖蛋白（P-gp）组成，该糖蛋白利用三磷酸腺苷形式的能量通过跨膜段形成的通道运输药物。目的：我们的目的是通过免疫细胞化学检测冷冻未经治疗的乳腺癌中P-gp的表达水平，并将这些水平与当前的预后指标相关联，在少数情况下，通过聚合酶链反应（PCR）将这些水平与MDR1（也称为PGY1） mRNA表达相关联。方法：采用针对P-gp的特异性单克隆抗体（JSB1）在213例乳腺癌5 μ m冷冻序列切片中检测P-gp多药耐药基因的免疫细胞化学表达。通过图像分析评估免疫染色制剂的显微图像，并与PCR评估的MDR1转录（mRNA）进行比较。定量P-gp免疫细胞化学检测与组织预后因素和免疫细胞化学指标相关。结果：213例乳腺癌中，仅P-gp阳性113例（53%），但28%的肿瘤免疫染色表面占总染色面积的不到5%。反映胞内P-gp抗原数量的定量免疫细胞化学强相关(r = 0.865
Background: Chemotherapy failure that is due to cellular drug resistance remains a major problem in most cancer patients. One type of drug resistance that has been characterized is the multidrug resistance phenomenon, which demonstrates a reduced ability of cancer cells to accumulate drugs as a result of the effects of an energy-dependent unidirectional drug efflux pump with a broad substrate specificity. This drug pump is composed of a 170-kd transmembrane glycoprotein referred to as the P-glycoprotein (P-gp) that uses energy in the form of adenosine triphosphate to transport drugs through a channel formed by transmembrane segments. Purpose: Our purpose was fo detect the levels of P-gp expression in frozen untreated breast carcinomas by immunocytochemical assays and to correlate these levels to current prognostic indicators and, in a few cases, to MDR1 (also known as PGY1) mRNA expression by polymerase chain reaction (PCR). Methods: The immunocytochemical expression of the multidrug resistance gene, P-gp, was investigated using a specific monoclonal antibody (JSB1) against P-gp in 5-mu m frozen sequential sections of breast carcinomas obtained from 213 patients. Microscopic images of immunostained preparations were evaluated by image analysis and were compared with MDR1 transcription (mRNA) assessed by PCR in 16 patients. Quantitative P-gp immunocytochemical assays were correlated to histoprognostic factors and immunocytochemical indicators. Results: Among the 213 breast carcinomas tested, 113 (53%) mere P-gp positive, but in 28% of the tumors, the immunostained surface accounted for less than 5% of the total area stained. Quantitative immunocytochemistry reflecting the amount of intracellular P-gp antigen strongly correlated (r = 0.865; two-sided, P