Abstract
The development of hepatocellular carcinoma (HCC) is a frequent event during the natural history of cirrhosis. Effective treatment is, however, hampered by drug resistance related to the expression of multidrug resistance (MDR) proteins belonging to the ABC family transporters. Studying expression of genes coding for these proteins may help to explain the potential sensitivity of HCC to chemotherapy. The expression of MRP1, MRP2, MRP3, MDR1, and MDR3 was investigated by quantitative RT-PCR analyses in paraffin-embedded tissues obtained from 9 cases of HCC, 16 cases of cirrhosis, 10 cases of chronic extrahepatic cholestasis, and 16 cases of normal liver. In HCC cases, gene expression was assessed both in neoplastic and perineoplastic tissue after microscopically assisted microdissection. MRP1 was significantly and similarly overexpressed in HCC and perineoplastic tissue. MRP2 and MDR1 were also increased in HCC, but the level of expression did not correlate with that of perineoplastic tissue. The level of expression was either reduced or normal in cirrhotic liver and during chronic cholestasis. Expression of MDR3 was unchanged in all conditions investigated. The genetic expression of multi-drug resistance proteins, in particular MRP1, MRP2, and MDR1, is increased during HCC. In the case of MRP1, the extent of expression is similar in neoplastic and perineoplastic tissue, but this is not the case for MRP2 and MDR1. The assessment of ABC protein expression pattern may provide important information for the diagnosis and treatment of HCC.
Highlights
Liver cirrhosis is a common disease, been detected in more that 1% of the general population [1,2,3]
We investigated the genetic expression of three MRPs (MRP1, 2 and 3) and two multidrug resistance (MDR) proteins (MDR1 and MDR3) in hepatocellular carcinoma (HCC) tissue as well as in the perineoplastic, nonneoplastic liver, and compared the expression with that found in cirrhotic subjects, in patient with extrahepatic cholestasis, and in subjects without liver disease
The expression of the mRNA of five ABC transporters was assessed in HCC, perineoplastic tissue, cirrhosis, and extrahepatic cholestasis; liver without sign of liver disease was used as control
Summary
Liver cirrhosis is a common disease, been detected in more that 1% of the general population [1,2,3]. Hepatocellular carcinoma (HCC) is a frequent complication in the natural history of advanced chronic liver disease. Treatment with one specific anticancer drug often results in cross-resistance against a broad range of structurally unrelated drugs. This phenomenon is known as multidrug resistance (MDR). The development of hepatocellular carcinoma (HCC) is a frequent event during the natural history of cirrhosis. Effective treatment is hampered by drug resistance related to the expression of multidrug resistance (MDR) proteins belonging to the ABC family transporters. Material and Methods: The expression of MRP1, MRP2, MRP3, MDR1, and MDR3 was investigated by quantitative RT-PCR analyses in paraffin-embedded tissues obtained from 9 cases of HCC, 16 cases of cirrhosis, 10 cases of chronic extrahepatic cholestasis, and 16 cases of normal liver. In HCC cases, gene expression was assessed both in neoplastic and perineoplastic tissue after microscopically assisted microdissection
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