MDR1 MESSENGER-RNA EXPRESSION BY RT-PCR IN PATIENTS WITH PRIMARY BREAST-CANCER SUBMITTED TO NEOADJUVANT THERAPY

mdr1 expression by reverse transcription and polymerase chain reaction (RT-PCR) has been compared to P-glycoprotein (Pgp) expression by immu nohistochemistry (IHC) and correlated with clinical response to neoadj uvant therapy. RNA has been recovered from glass slide smears of fine- needle aspiration from 57 untreated primary breast cancers prior to ne oadjuvant chemotherapy (33 cases),hormone therapy (23 cases), or both (1 case). Furthermore, mdr1 mRNA has been analyzed in 6 cases after 2 months of treatment. The neoadjuvant therapy consisted of 4 cycles of adriamycin and cyclophosphamide or tamoxifen. Of 57 tumor specimens, a n interpretable result was obtained in 52 cases, indicating the feasib ility of the analysis by RT-PCR with very small tumor specimens. The p resence of mdr1 mRNA has been documented in 44/52 (84%) tumor samples with a spectrum of expression levels. The expression of mdr1 mRNA was compared with P-glycoprotein (Pgp) expression by IHC using JSB-1, 4E3, and C494 monoclonal antibodies in 48 of the 52 interpretable tumor sa mples. 12/48 (25%) expressed Pgp by IHC. All tumors expressing Pgp by IHC were also positive by RT-PCR. The results confirm the higher preva lence of mdr1 mRNA compared to the protein expression. However, mdr1 m RNA expression was found to correlate significantly with resistance to neoadjuvant hormone therapy only while Pgp expression detected by JSB -1 immunostaining only correlated with chemoresistance. The lack of co nvincing correlation with chemoresistance suggests that mRNA and Pgp m ay not be directly or solely responsible for clinical response to drug s. Further studies should focus on the posttranslational modulation of P-glycoprotein and other mechanisms of drug resistance.