The prognostic significance of expression of the multidrug resistance-associated protein (MRP) in primary breast cancer.
The prognostic significance of expression of the multidrug resistance-associated protein (MRP) in primary breast cancer.
复制标题
多药抗性相关蛋白（MRP）在原发性乳腺癌中表达的预后意义。
DOI：
10.1038/bjc.1997.414
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发表时间：
1997
影响因子：
8.8
通讯作者：
Foekens, J A
中科院分区：
文献类型：
--
作者：
Nooter, K;Brutel de la Riviere, G;Look, M P;van Wingerden, K E;Henzen-Logmans, S C;Scheper, R J;Flens, M J;Klijn, J G;Stoter, G;Foekens, J A
在本研究中，我们通过单克隆抗体免疫组化测定了259例切除的原发性浸润性乳腺癌中MRP蛋白表达的频率和强度，并评估了MRP免疫反应性与患者和肿瘤特征、无复发（RFS）和总生存期（OS）的关系。免疫染色以半定量量表进行分级，范围为（-）至（）。总体而言，34%的肿瘤抗MRP抗体阳性：19%显示弱细胞质染色（+），14%具有清晰的细胞质染色（++），仅1%的肿瘤具有强细胞质和膜染色（）。MRP表达与患者年龄、绝经状态、肿瘤大小、分化程度、雌孕激素受体水平及淋巴结转移无关。在所有患者的探索性单变量分析中，只有原发肿瘤大小和累及淋巴结数量与缩短RFS（分别为P < 0.001和P < 0.001）和OS（分别为P = 0.02和P < 0.001）显著相关。在按绝经状态、肿瘤大小、淋巴结状态、辅助全身治疗和雌激素和孕激素受体状态分层的患者亚组中，RFS的考克斯单变量分析中，MRP表达与接受环磷酰胺、甲氨蝶呤和5-氟尿嘧啶（CMF）辅助全身化疗的小肿瘤患者（T1）、淋巴结阴性患者和淋巴结阳性患者的失败风险增加相关;在MRP存在下，复发的相对危险率（RHR）增加，RHR值的95%置信限（CL）分别为2.8（1.2-6.9）、2.1（1.0-4.2）和2.8（0.8-9.9）。在OS分析中，MRP的表达也与小肿瘤患者（T1）失败风险增加相关[RHR（95%CL）2.3（0.9-6.0）]和接受CMF辅助全身化疗的淋巴结阳性患者[RHR（95%CL）3.7（0.8-17.1）]，但在淋巴结阴性患者中未发现[RHR（95% CL）1.1（0.4-2.6）]。总之，我们的研究结果表明，MRP是经常过度表达的原发性乳腺癌，并建议MRP表达可能是预后意义的亚组的患者更有利的预后，即小肿瘤患者和淋巴结阴性患者，以及在设置辅助全身化疗。在原发性乳腺癌中，MRP可能与细胞生物学行为改变有关，包括更具侵袭性的表型，以及对辅助全身化疗的抵抗。
In the present study, we determined the frequency and intensity of MRP protein expression by monoclonal antibody immunohistochemistry in a series of 259 resected invasive primary breast carcinomas, and we evaluated MRP immunoreactivity in relation to patient and tumour characteristics, relapse-free (RFS) and overall survival (OS). The immunostaining was graded on a semiquantitative scale that ranged from (-) to ( ). Overall, 34% of the tumours were positive for anti-MRP antibody: 19% showed weak cytoplasmic staining (+), 14% had clear cytoplasmic staining (++) and only 1% of the tumours had a strong cytoplasmic as well as membranous staining ( ). MRP expression was not related to patient's age, menopausal status, tumour size, differentiation grade, oestrogen and progesterone receptor level or lymph node involvement. In an exploratory univariate analysis of all patients, only primary tumour size and number of lymph nodes involved were significantly associated with shortened RFS (P < 0.001 and P < 0.001 respectively) and OS (P = 0.02 and P < 0.001 respectively). In Cox univariate analysis for RFS in subgroups of patients stratified by menopausal status, tumour size, nodal status, adjuvant systemic therapy and oestrogen and progesterone receptor status, MRP expression was associated with increased risk for failure in patients with small tumours (T1), in node-negative patients and in node-positive patients who received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF); the relative hazard rate (RHR) for relapse was increased in the presence of MRP, with RHR values with 95% confidence limits (CL) of 2.8 (1.2-6.9), 2.1 (1.0-4.2) and 2.8 (0.8-9.9) respectively. In analysis for OS, expression of MRP was also associated with increased risk for failure in patients with small tumours (T1) [RHR (95% CL) 2.3 (0.9-6.0)] and in node-positive patients who received adjuvant systemic chemotherapy with CMF [RHR (95% CL) 3.7 (0.8-17.1)] but not in node-negative patients [RHR (95% CL) 1.1 (0.4-2.6)]. In conclusion, our results show that MRP is frequently overexpressed in primary breast cancer and suggest that MRP expression might be of prognostic significance in the subgroups of patients with the more favourable prognosis, i.e. patients with small tumours and node-negative patients, as well as in the setting of adjuvant systemic chemotherapy. In primary breast cancer, MRP might be related to altered cell biological behaviour, including a more aggressive phenotype, and resistance to adjuvant systemic chemotherapy.