Differential expression of drug metabolizing enzymes in primary and secondary liver neoplasm: immunohistochemical characterization of cytochrome P4503A and glutathione-S-transferase.
The question whether expression of drug metabolizing enzymes in human liver is altered by liver neoplasm remains controversial; however, the ability or unability of tumour cells to metabolize certain drugs may be important for developing therapeutic strategies. We therefore investigated the abundance and localization of two classes of drug metabolizing enzymes [cytochrome P4503A (CYP3A) and pi-type glutathione-S-transferase] by means of immunohistochemistry (standard ABC technique) in patients with hepatocellular carcinoma (HCC, n = 16) and with liver metastasis from adenocarcinoma (n = 53) in comparison to normal controls (n = 5). The distribution of CYP3A in normal liver samples showed a characteristic pattern of four to five layers of stained hepatocytes surrounding the central vein. Eleven out of 16 cases of HCC showed expression of CYP3A; staining was less intense than in normal liver and zonation was completely lost. In contrast, only 5 out of 53 samples of metastasis stained positively for CYP3A. The difference between primary and secondary neoplasm was statistically significant (chi-square, P < 0.0001). Pi-type glutathione-S-transferase (GST) stained positively in 9 out of 16 HCC and in 48 out of 53 cases of liver metastasis (chi-square, P < 0.01) indicating a higher percentage of immunostaining in liver metastasis. In summary, we observed differences in the abundance and distribution pattern of CYP3A and GST between primary and secondary neoplasma of human liver and in comparison to normal controls. In combination with established methods these data may contribute to the establishment of reliable test systems for distinguishing primary from secondary liver tumours.(ABSTRACT TRUNCATED AT 250 WORDS)
Fritz
P
P
Pathologisches Institut am Robert-Bosch-Krankenhaus, Stuttgart, Germany.
Behrle
E
E
Beaune
P
P
Eichelbaum
M
M
Kroemer
H K
HK
D000230:Adenocarcinoma / Q000201:enzymology* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000032:analysis*; D012680:Sensitivity and Specificity
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase