Journal
APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
Volume 10, Issue 4, Pages 374-380Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00022744-200212000-00015
Keywords
carboxylesterase-2; human normal tissues; immunohistochemistry; tissue array
Funding
- NCI NIH HHS [CA091842] Funding Source: Medline
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Carboxylesterases play an important role in the hydrolytic biotransformation of a number of structurally diverse endogenous compounds and medications. Several distinct carboxylesterase isoforms have been described in human liver, brain, and placenta. Carboxylesterase-2 has been identified as the key enzyme in the metabolic activation of the irinotecan, a topoisomerase I inhibitor commonly used in the treatment of many solid tumors. The tissue distribution and intensity of protein expression of carboxylesterase-2 have not been defined in any organ or tissue. This study used a carboxylesterase-2-specific antibody and tissue array analysis to detect carboxylesterase-2 expression in human normal tissues by immunohistochemistry. Carboxylesterase-2 is present in a wide variety of organs and tissues. The highest carboxylesterase-2 expression occurs in hepatocyte, small intestine mucosa, kidney proximal convoluted tubule, and adrenal cortex cells. The results suggest that liver and gastrointestinal tract with carboxylesterase-2 are likely the most important sites of conversion of irinotecan to the active metabolite SN-38, but carboxylesterase-2 within the other tissues may be contributive to this process. In the central nervous system, carboxylesterase-2 expression was confined to capillary endothelial cells, consistent with the enzyme having a role to protect the central nervous system from toxic esters and perhaps being a component of a blood-brain barrier system.
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