Abstract
Recurrence following failure of chemotherapy limits the application of high doses of anticancer drugs currently used for eliminating cancerous cells. It has been identified that ATP-binding cassette (ABC) multidrug transporters are associated with chemoresistance, which is a major obstacle in cancer therapy. The present study aimed to investigate the association of pretherapeutic multidrug resistance-associated protein 2 (MRP2) expression with response to chemotherapy in stage II/III colorectal cancer (CRC). Protein expression was determined by immunohistochemical analysis of 50 archival samples from patients who had not received preoperative chemotherapy and radiotherapy. All patients were treated with 5-fluorouracil/leucovorin (FL) plus oxaliplatin (FOLFOX-4) regimen for 6 months following curative resection. During the 12 months of follow-up, local and distant recurrences were observed in 15 (30%) cases, of which 5 occurred at the time of chemotherapy. MRP2 expression was observed in 24 (48%) and 7 (14%) cases in the tumor tissues and matched normal tissues, respectively. A significant difference was observed between the positive expression frequency in the tumor tissues compared to the surrounding normal mucosa (P=0.003). The incidence of recurrence and metastasis for patients in the MRP2-positive group was lower than that in the MRP2-negative group (P>0.05); however, all 5 cases who demonstrated recurrence during their treatment were MRP2-positive (P=0.022). MRP2 expression was not correlated with the clinicopathological markers in this group of patients. Kaplan-Meier analysis revealed that MRP2 expression was not associated with a shorter disease-free survival or overall survival of patients (P>0.05). The results of this study indicated that MRP2 is overexpressed in the course of CRC development and progression. However, expression of MRP2 was not associated with recurrence of patients treated with FL and oxaliplatin in the population studied.