The cancer marker neutrophil gelatinase-associated lipocalin is highly expressed in human endometrial hyperplasia

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Neutrophil gelatinase-associated lipocalin (NGAL) is highly expressed in human endometrial hyperplasia, correlating with specific cancer-related genes like COX-2 and E-cadherin.

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This study evaluated neutrophil gelatinase-associated lipocalin (NGAL/LCN2) expression and its relationship to pathogenic cytokines and cancer-related genes (including COX-2, E-cadherin, β-catenin, and vimentin) in endometrial disorders using Western blotting, immunohistochemistry, and RT-PCR on biopsy samples from patients with endometrial hyperplasia versus endometrial adenomyosis. Immunohistochemistry showed NGAL in glandular epithelial cells but not stromal cells of hyperplasia, and NGAL protein and mRNA levels were significantly higher in hyperplasia than in adenomyosis. The authors found no differences in pathogenic cytokines between groups, while COX-2, β-catenin, vimentin, and E-cadherin were highly expressed in hyperplasia, with NGAL mRNA correlating positively with COX-2 and E-cadherin and negatively with vimentin and β-catenin. The study explicitly compares hyperplasia to adenomyosis but does not provide a direct mechanistic experiment demonstrating NGAL’s proposed role in preventing progression to carcinoma. This paper is centrally about endometriosis and/or adenomyosis-related pathology insofar as it includes endometrial adenomyosis as the comparison group and reports that NGAL is more highly expressed in endometrial hyperplasia than in adenomyosis.

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Abstract

Recently, endometrial hyperplasia was identified as presenting a higher risk for progressing to endometrial carcinoma more readily than adenomyosis. The Lcn-2 gene encodes neutrophil gelatinase-associated lipocalin (NGAL), which promotes cell proliferation and serves as a cancer marker in some cancers. In our current study, we investigated the relationship between the expression of NGAL and that of pathogenic cytokines and cancer-related genes including cyclooxygenase-2 (COX-2), E-cadherin, β-catenin, and vimentin in patients with endometrial disorders. NGAL expression was examined by Western blotting, immunohistochemistry, and reverse-transcription polymerase chain reaction (RT-PCR) in hyperplasia and adenomyosis biopsy samples. Immunohistochemistry demonstrated the occurrence of NGAL in glandular epithelial cells but not in the stromal cells of hyperplasia biopsy samples. NGAL protein and mRNA expression were significantly greater in endometrial hyperplasia than in endometrial adenomyosis. Although our data showed no difference in pathogenic cytokines between patients with endometrial hyperplasia and endometrial adenomyosis, we observed high expression levels of COX-2, β-catenin, vimentin, and E-cadherin in patients with endometrial hyperplasia. NGAL mRNA expression correlated positively with COX-2 and E-cadherin mRNA expression (r = 0.41 and r = 0.57, respectively), but correlated negatively with vimentin and β-catenin mRNA expression (r = -0.42 and r = -0.61, respectively). Our data suggest that NGAL is up-regulated in patients with endometrial hyperplasia to prevent the transition from hyperplasia to carcinoma.
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Abstract

Recently, endometrial hyperplasia was identified as presenting a higher risk for progressing to endometrial carcinoma more readily than adenomyosis. The Lcn-2 gene encodes neutrophil gelatinase-associated lipocalin (NGAL), which promotes cell proliferation and serves as a cancer marker in some cancers. In our current study, we investigated the relationship between the expression of NGAL and that of pathogenic cytokines and cancer-related genes including cyclooxygenase-2 (COX-2), E-cadherin, β-catenin, and vimentin in patients with endometrial disorders. NGAL expression was examined by Western blotting, immunohistochemistry, and reverse-transcription polymerase chain reaction (RT-PCR) in hyperplasia and adenomyosis biopsy samples. Immunohistochemistry demonstrated the occurrence of NGAL in glandular epithelial cells but not in the stromal cells of hyperplasia biopsy samples. NGAL protein and mRNA expression were significantly greater in endometrial hyperplasia than in endometrial adenomyosis. Although our data showed no difference in pathogenic cytokines between patients with endometrial hyperplasia and endometrial adenomyosis, we observed high expression levels of COX-2, β-catenin, vimentin, and E-cadherin in patients with endometrial hyperplasia. NGAL mRNA expression correlated positively with COX-2 and E-cadherin mRNA expression (r = 0.41 and r = 0.57, respectively), but correlated negatively with vimentin and β-catenin mRNA expression (r = −0.42 and r = −0.61, respectively). Our data suggest that NGAL is up-regulated in patients with endometrial hyperplasia to prevent the transition from hyperplasia to carcinoma. Similar content being viewed by others

References

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Mol Biol Rep 39, 1029–1036 (2012). https://doi.org/10.1007/s11033-011-0828-9 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s11033-011-0828-9

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Condition tags

endometriosisadenomyosis

MeSH descriptors

Acute-Phase Proteins Biomarkers, Tumor Endometrial Hyperplasia Endometriosis Lipocalins Proto-Oncogene Proteins Acute-Phase Proteins Analysis of Variance beta Catenin beta Catenin Biomarkers, Tumor Blotting, Western Cadherins Cadherins Cyclooxygenase 2 Cyclooxygenase 2 DNA Primers DNA Primers Endometrial Hyperplasia Endometriosis

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