Markers of drug resistance in relapsing colon cancer

Purpose: 5-Fluorouracil failure and drug resistance. which often occurs during chemotherapy. is still a great obstacle to the success of human colon cancer treatment. Thus. the comparative study of markers of drug resistance in cancer cells before and after chemotherapy may be extremely helpful in the selection of the appropriate chemotherapeutic drug in colon cancer patients who fail adjuvant treatment with 5-fluorouracil. In the present study we examined the differential expression of three multidrug resistance-related proteins (i.e., P-glycoprotein, MRP, and LRP) and of topoisomerase IIalpha in a series of 20 primary colon carcinomas and their recurrences. Methods: All markers were determined at tissue level by three-step immunohistochemistry using appropriate monoclonal antibodies. and the markers’ immunopositivity was quantified by image analysis. In addition. Feulgen stain was used for the assessment of nuclear DNA content of malignant cells at their primary location. Results: Some degree of aneuploidy was detected in all primary carcinomas. The immunoexpression of the three multidrug resistance-related proteins did not change significantly, either qualitatively (positivity vs negativity) or quantitatively, after chemotherapy. On the contrary, the percentages of topoisomerase IIalpha-positive malignant cells were significantly increased in the tumour recurrences by comparison to their primary locations (P = 0.011). Conclusions: According to our results. increased topoisomerase IIalpha immunohistochemical expression appears to be part of the malignant cells’ phenotype in recurrent colon cancers. Therapeutic options after failure of 5-fluorouracil-based treatment could therefore include appropriate topoisomerase IIalpha-targeted drugs

Multidrug resistance proteins and topoisomerase II alpha expression in colon cancer: association with metastatic potential

Aims: To investigate the role of multidrug resistance proteins and topoisomerase IIalpha in colon cancer. Methods: Tissue sections from 89 Dukes’ stage B-D colon cancer patients were selected. The expression of multidrug resistance proteins and topoisomerase IIalpha in primary tumour cells was assessed by standard immunohistochemistry. The extent of their expression was measured by image analysis and was correlated with clinicopathological features of the patients. Results: P-glycoprotein was associated with the presence of lymph node metastasis (P=0.005), vessel invasion (P=0.0001) and perineural invasion (P=0.020). Conclusions: P-glycoprotein is probably involved in the processes of local invasion and metastatic dissemination