Aberrant intranuclear localization of biotin, biotin-binding enzymes, and β-catenin in pregnancy-related endometrium and morule-associated neoplastic lesions

Biotin-rich intranuclear inclusions, also known as optically clear nuclei have been observed in various neoplastic and non-neoplastic lesions. They look like nuclei of herpesvirus-infected cells and cause a false-positive immunohistochemical result by avidin-biotin-complex (ABC) method. In the literature, all types of neoplastic lesions with intranuclear inclusions, with one exception, have been characteristically associated with squamoid structures known as morules. By contrast, all reported nonneoplastic lesions with such inclusions lacked morules and were confined to pregnancy-related endometrium. In the present study, adding unreported types of morule-associated neoplastic lesions, we investigated the distribution of biotin, biotin-binding enzymes, and beta-catenin in these lesions by immunohistochemical staining. We detected the intranuclear localization of biotin and of two mitochondrial biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase) in all lesions examined, regardless of whether they were neoplastic or non-neoplastic and irrespective of the presence or absence of morules. The intranuclear localization of beta-catenin was detected in all neoplastic lesions with mondes and in ovarian endometrioid adenocarcinoma. without morules, but not in non-neoplastic endometrial lesions. These results suggest the following conclusions: (1) lesions with biotin-rich intranuclear inclusions can be classified as non-neoplastic/pregnancy-related endometrial and as neoplastic/pregnancy-unrelated or morular category, (2) the intranuclear biotin in both types of lesion is found in conjunction with biotin-binding enzymes. However, the role of beta-catenin in morule-associated neoplastic lesions, the relationship between beta-catenin and biotin/ biotin-binding enzymes, and the mechanism of migration of biotin and biotin-binding enzymes from the cytoplasm to the nucleus remain unclear.