Ro J, Sahin A, Ro J Y, Fritsche H, Hortobagyi G, Blick M
Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Hum Pathol. 1990 Aug;21(8):787-91. doi: 10.1016/0046-8177(90)90046-8.
We analyzed the expression of P-glycoprotein in samples from 48 patients with locally advanced breast cancer. Tumor samples from 40 patients were obtained at mastectomy, which was performed after three cycles of induction chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine, and prednisone. P-glycoprotein expression distributed focally was observed in 20 tumors by the immunoperoxidase method using the anti-p170-monoclonal antibody C219. The percentage of the tumor cell population expressing P-glycoprotein varied from less than 5% to greater than 30%; expression was observed significantly more often in tumors that showed less than partial response to the preoperative chemotherapy. Furthermore, P-glycoprotein was not expressed in eight tumor specimens obtained at the time of diagnosis, prior to chemotherapy, from patients who subsequently had pathologic complete responses. A comparative study of P-glycoprotein expression before and after chemotherapy and upon recurrence of tumor was done on a limited number of samples. No significant differences in P-glycoprotein expression were found. Therefore, it is possible that an intrinsic, rather than acquired, drug resistance may play a role in the failure of induction chemotherapy for locally advanced breast cancer.
我们分析了48例局部晚期乳腺癌患者样本中P-糖蛋白的表达情况。40例患者的肿瘤样本是在乳房切除术中获取的,乳房切除术在由阿霉素、环磷酰胺、长春新碱和强的松组成的三个诱导化疗周期后进行。使用抗p170单克隆抗体C219通过免疫过氧化物酶法在20个肿瘤中观察到P-糖蛋白表达呈局灶性分布。表达P-糖蛋白的肿瘤细胞群体百分比从小于5%到大于30%不等;在对术前化疗显示出不完全缓解的肿瘤中,这种表达明显更常见。此外,在化疗前诊断时从随后出现病理完全缓解的患者中获取的8个肿瘤标本中未检测到P-糖蛋白表达。对有限数量的样本进行了化疗前后以及肿瘤复发时P-糖蛋白表达的比较研究。未发现P-糖蛋白表达有显著差异。因此,内在的而非获得性的耐药性可能在局部晚期乳腺癌诱导化疗失败中起作用。