IMMUNOHISTOCHEMICAL DETECTION OF P-GLYCOPROTEIN - PROGNOSTIC CORRELATION IN SOFT-TISSUE SARCOMA OF CHILDHOOD
IMMUNOHISTOCHEMICAL DETECTION OF P-GLYCOPROTEIN - PROGNOSTIC CORRELATION IN SOFT-TISSUE SARCOMA OF CHILDHOOD
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DOI：
10.1200/jco.1990.8.4.689
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发表时间：
1990-04-01
影响因子：
45.3
通讯作者：
LING, V
中科院分区：
文献类型：
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作者：
CHAN, HSL;THORNER, PS;LING, V
在许多细胞系中，P-糖蛋白的表达增加与多药耐药（MDR）相关。已在许多人类肿瘤中检测到显著水平的P-糖蛋白。本研究的目的是确定P-糖蛋白表达是否与儿童软组织肉瘤的化疗反应和预后相关。在一项回顾性研究中，采用半定量免疫组织化学方法分析了在多伦多儿童医院治疗的30例横纹肌肉瘤（RMS）和未分化肉瘤（US）的活检标本。在9例患者中检测到P-糖蛋白，其中4例在诊断时检测到，5例在随后的活检中检测到。所有9名患者在对化疗有临床反应（完全[CR] 55，部分[PR] 45%）后复发。21例持续P-糖蛋白阴性肿瘤患者中有20例接受了化疗，他们都有临床反应（CR 80%，PR 20%）。这20名患者中只有1人复发。肿瘤中含有可检测水平的P-糖蛋白的化疗患者（n = 9）与肿瘤中不含可检测水平的P-糖蛋白的化疗患者（n = 20）相比，无复发生存率有显著差异（P <.00000012）。这两组的总体生存概率也有显著差异（P <0.0000267）。两组患者的无复发生存率和总生存率在调整分期和部位差异后，采用对数秩法分析时仍有统计学差异。两组其他不良预后因素的发生率，例如，年龄较小和较大，治疗前淋巴细胞计数低，肿瘤较大和组织学不良无显著差异。因此，可检测到的P-糖蛋白似乎是软组织肉瘤儿童的一个重要不良预后因素，并且该蛋白的持续缺乏与良好的预后相关。
Increased expression of P-glycoprotein is associated with multidrug resistance (MDR) in many cell lines. Significant levels of P-glycoprotein have been detected in a number of human tumors. The purpose of this study was to determine whether P-glycoprotein expression correlates with both responses to chemotherapy and prognosis in soft tissue sarcoma of childhood. In a retrospective study, biopsy samples from 30 cases of rhabdomyosarcoma (RMS) and undifferentiated sarcoma (US) treated at The Hospital for Sick Children in Toronto were analyzed using a semiquantitative immunohistochemical procedure. P-glycoprotein was detected in nine patients, four at diagnosis, and five at subsequent biopsy. All nine patients relapsed after a clinical response (complete [CR] 55, partial [PR] 45%) to chemotherapy. Twenty of 21 patients with consistently P-glycoprotein-negative tumors received chemotherapy and they all responded clinically (CR 80%, PR 20%). Only one of these 20 patients has relapsed. The probability of relapse-free survival was significantly different (P < .000000012) in chemotherapy-treated patients whose tumors contained detectable levels of P-glycoprotein (n = 9), compared with those whose tumors contained no detectable P-glycoprotein (n = 20). The overall probability of survival was also significantly different in these two groups (P < .0000267). Both relapse-free and overall survivals remained statistically different in the two groups of patients when analyzed by the log-rank method, after adjustment for differences in stages and sites. The incidence of other adverse prognostic factors in the two groups, for example, younger and older ages, low pretreatment lymphocyte counts, large tumors, and unfavorable histology were not significantly different. Thus, detectable P-glycoprotein appears to be an important adverse prognostic factor in children with soft tissue sarcoma, and consistent absence of the protein was associated with a favorable prognosis.