| Object: Lung resistance protein (LRP) is a molecular newly found in recent years associated with multidrug resistance. As the major vault protein in human, it may mediate multidrug resistance by regulating the nuclecytoplasmic and vesicular transport of drugs. LRP expression has been found in several malignant blood diseases such like acute leukemia, multiple myeloma and other tumors such like ovarian carcinoma, malignant melanoma and so on. Multidrug resistance is a common phenomenon in non-Hodgkin's lymphoma(NHL).The aim of this passage is to determine the expression and clinical relevance of LRP in NHL, and the relation with another drug resistance molecular: multidrug resistance-associated protein(MRP).Patients: Twenty-eight NHL patients with initial biospies were included in this study. All were treated with CHOP and evaluated response to chemotherapy after 3-6 cycles. Among them, there were 13 males, 15 females, and 9 low grade, 9 middle grade and 10 high grade patients.Methods: LRP and MRP expression was immunohischemically assessed by means of monocloneantibody LRP-56 and OCTL-1 with dilution 1:30 and l:50.The positive standard for LRP was at least 10% of the cells presented yellow-brown staining as a cytoplasmic pattern while a cytoplamic and/or memberance pattern for MRP. Fisher's Exact Test and Corrected Spearman Rank Correlation were used for statistic analysis.Results: 1. LRP and MRP Expression in NHL at Diagnosis: LRP staining ranged from 0-80%. LRP was positive in 11 of 28 NHL patients, positive rate was 39%.MRP staining ranged from 0-40%, MRP was positive in 6 of 28 specimens, positive rate was 21%.2. Correlation of LRP and MRP with Clinical Characteristics: There was no significant association between LRP expression and age, sex, stage, cellular origin. LRP expression was more frequently observed in patients with middle and high tumor grade than those with low grade(P=0.0389). MRP expression was independent of age, sex, cellular origin, stage and tumor grade.3. There was no correlation of LRP and MRP expression (rs=0.065, P>0.5).4. LRP and MRP expression and Response to Chemotherapy: The complete response (CR) rate of the total study was 18% for LRP-positive patients while 82% for LRP-negative patients (P=0.0184). The CR rate was 55% for MRP-positive patients and 33% for MRP-negative patients, the different was not significant (P>0.10). None of the threepatients with LRP and MRP both positive reached CR, 2 of the 8 patients with LRP single positive got CR, CR rate was 25% there was no significant difference (P>0.1). The difference of CR rate between patients with LRP positive and strong positive was not significant (P>0.1).5. There was no significant difference of LRP and MRP expression between patients before and after treatment.6. Correlation of Response to Chemotherapy and Clinical Characteristics: Besides LRP, the CR rate was also correlation with tumor grade. Low-grade patients had a higher CR rate than middle and high-grade patients (P=0.0458).Conclusion: LRP expression may be an important mechanism in multidrug resistance in previous untreated NHL.MRP has no impact on outcome of NHL and with no correlation with clinical characteristics and expression of LRP. The development of strategies to clinically overcome LRP-mediated drug resistance might improve outcome of NHL therapy. Studies of other mechanisms of drug resistance in NHL are warranted. |
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