The Multidrug Resistance-related Protein and P-glycoprotein Expressions, and the Washout Rates of 99mTc-MIBI in Infiltrating Ductal Carcinoma of Breast, Correlation with the Response After Neoadjuvant Chemotherapy / 한국유방암학회지

PURPOSE: Numerous non-invasive imaging methods for evaluating the chemotherapy response of breast cancer patients are currently being explored. The aim of present study was to investigate whether the washout rates (WRs) of 99mTc-MIBI could predict the response to chemotherapy in patients suffering with infiltrating ductal carcinoma using the expressions of multidrug resistance-related protein (MRP) and P-glycoprotein (Pgp). METHODS: From May 2002 and March 2004, the patients were randomly and consecutively selected according to the results of immunohistochemical analyses of breast carcinoma specimens before the administration of neoadjuvant chemotherapy. A total 45 infiltrating ductal carcinomas in 45 female patients were selected and they were separated into three groups: group A consisted of tumors with both negative Pgp and MRP expressions (n=15); group B consisted of the tumors that were positive for either a Pgp expression or a MRP expression (n=15); group C consisted of the tumors that were positive for both Pgp and MRP expressions (n=15). All the patients were referred for double phase 99mTc-MIBI mammoscintigraphy after the injection of 925 MBq of 99mTc-MIBI to calculate the WR. The tumor response was evaluated after completion of neoadjuvant chemotherapy. The tumor response was classified as a complete or partial response (the responder group) and stable or progression (the non-responder group). All the patients underwent surgery. RESULTS: The response rate of group C was lower than that of the other groups, but the difference was not statistically significant (p=0.283). The WR of non-responder group was lower than that of the responder group, although the difference was not statistically significant (p=0.674). The washout rates of group C was the highest than other groups and the difference was statistically significant (p=0.001). CONCLUSION: In conclusion, the WR of 99mTc-MIBI is helpful for in vivo determination of both the Pgp and MRP expressions for infiltrating ductal carcinoma of the breast.

Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia

The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.