Immunohistochemical analysis of P-glycoprotein expression correlated with chemotherapy resistance in locally advanced breast cancer.
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.
Ro
J
J
Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Sahin
A
A
Ro
J Y
JY
Fritsche
H
H
Hortobagyi
G
G
Blick
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004351:Drug Resistance / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012008:Recurrence; D014750:Vincristine / Q000008:administration & dosage
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone