060 MRP1, -3 and -5 protein expression in non-small cells carcinomes and survey after adjuvant chemotherapy

Introduction Non-small cell lung carcinomas (NSCLC) are characterized by their intrinsic resistance to chemotherapy. The Multidrug Resistance Protein (MRP) family belong to the ATP bin-ding cassette super family of transport proteins, which play a physiological role in defence against toxic compounds including carcinogens. Some MRPs hâve been shown to confer resistance to anticancer agents in various in vitro models. Methods In order to investigate the possible role of MRP1, -3 and -5 in clinical drug resistance, protein expression is analysed using immunohistochemistry on tumoral tissue section from patient who underwent surgery. Survival is analysed according to MRP expression using Kaplan-Meier analysis and a Log Rank test. MRP gene expression using RT-PCR is already in progress. Results 61 tumoral frozen samples are used, 25 adenocarcino-mas (ADK) and 36 squamous cell carcinomas (SCC), collected from July 1998 to April 2004. 28 samples corne from patients who underwent adjuvant chemotherapy for an upgraded postoperative tumor. 35 tumorals samples do not express MRP1, -3 or -5. For the positive sample investigated, MRP3 is positive for ail ADK, MRP1 and -5 are inconstantly expressed. For the positive SCC, ail samples except one, are positive for MRP1, and only one sample hâve positive expression for MRP5 and for MRP3. Survival analysed using Kaplan-Meier analysis and a Log Rank test for the 28 patients who underwent adjuvant chemotherapy show that overall median survival is 20 months. Median survival for the patient who hâve none positive MRP expression is 65 months and for patients who hâve at less one positive MRP protein expression, the median survival is 16 months. This difference is not statistically significant (small sample size). Conclusions Only 42,6% of samples hâve a positive expression for at less one of the MRP, ADK express constantly MRP3 and SCC express MRPlmajoritary. The median survival for patient who underwent adjuvant chemotherapy decrease from 65 to 16 months, when at less one MRP is expressed. This suggest that MRP could be involved in chemotherapy response. More samples are investigated to confort these results and MRPs gene expression are also investigated and quantified using RT-PCR for these patients.