Can Immunohistochemistry of Multidrug-Resistant Proteins Replace the Histoculture Drug Response Assay in Colorectal Adenocarcinomas?

Abstract

Background/Aims: To investigate 1) whether immunohistochemistry of multidrug-resistant (MDR) proteins (MDR1, MRP1, MRP2 and BCRP) in colorectal adenocarcinomas can substitute for histoculture drug response assays (HDRA) and 2) whether chemosensitivity as indicated by HDRA and MDR protein expression is related to prognostic parameters in colorectal cancers. Methodology: Chemosensitivity of cancer tissues to 5-FU, irinotecan and oxaliplatin was assessed by HDRA. Immunohistochemical staining of MDR proteins was quantified by image analysis in 76 colorectal adenocarcinoma patients. Results: Inhibition rates (IRs) of the anticancer drugs by HDRA were not related to MDR protein expression. However, the IR of 5-FU was significantly decreased with lymph node metastasis (p=0.03) and advanced clinical stages (p=0.047). The IRs of irinotecan and oxaliplatin were not associated with clinicopathological parameters. Immunohistochemically, positive scores for MRP2 and BCRP protein were paradoxically related to lower clinical stages (p=0.043) and male gender (p=0.019), respectively. Conclusions: Immunohistochemical staining of MDR proteins can not predict tumor responses to anticancer drugs in colorectal cancers. Chemoresistance to 5-FU as indicated by HDRA was highly associated with aggressive prognostic factors.