Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice
<i>Background and Objectives</i>: FK506 binding protein like (FKBPL) is a member of the immunophilin family, with anti-angiogenic effects capable of inhibiting the migration of endothelial cells and blood vessel formation. Its role as an inhibitor of tumor growth and angiogenesis has pre...
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MDPI AG
2022-09-01
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| Online Access: | https://www.mdpi.com/1648-9144/58/10/1330 |
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| author | Danilo D. Obradović Nataša M. Milić Nenad Miladinović Lana McClements Dejan M. Oprić |
| author_facet | Danilo D. Obradović Nataša M. Milić Nenad Miladinović Lana McClements Dejan M. Oprić |
| author_sort | Danilo D. Obradović |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: FK506 binding protein like (FKBPL) is a member of the immunophilin family, with anti-angiogenic effects capable of inhibiting the migration of endothelial cells and blood vessel formation. Its role as an inhibitor of tumor growth and angiogenesis has previously been shown in studies with breast and ovarian cancer. The role of FKBPL in angiogenesis, growth, and carcinogenesis of endometrioid endometrial carcinoma (EEC) is still largely unknown. The aim of this study was to examine the expression of FKBPL in EEC and benign endometrial hyperplasia (BEH) and its correlation with the expression of vascular endothelial factor-A (VEGF-A) and estrogen receptor alpha (ERα). <i>Materials and Methods</i>: Specimens from 89 patients with EEC and 40 patients with BEH, as well as histological, clinical, and demographic data, were obtained from the Clinical Hospital Centre Zemun, Belgrade, Serbia over a 10-year period (2010–2020). Immunohistochemical staining of the tissue was performed for FKBPL, VEGF-A, and ERα. Slides were analyzed blind by two pathologists, who measured the intensity of FKBPL and VEGF-A expression and used the Allred score to determine the level of ERα expression. <i>Results</i>: Immunohistochemical analysis showed moderate to high intensity of FKBPL expression in 97.5% (<i>n</i> = 39) of samples of BEH, and low or no expression in 93.3% (<i>n</i> = 83) of cases of EEC. FKBPL staining showed a high positive predictive value (98.8%) and a high negative predictive value for malignant diagnosis (86.7%). The difference in FKBPL expression between EEC and BEH was statistically significant (<i>p</i> < 0.001), showing a decrease in intensity and loss of expression in malignant tissues of the endometrium. FKBPL expression was positively correlated with ERα expression (intensity, percentage and high Allred score values) and negatively correlated with the expression of VEGF-A (<i>p</i> < 0.05 for all). <i>Conclusions</i>: FKBPL protein expression demonstrated a significant decrease in FKBPL in EEC in comparison to BEH tissue, with a high predictive value for malignancy. FKBPL might be emerging as a significant protein with antiangiogenic and antineoplastic effects, showing great promise for the diagnostic and therapeutic applications of its therapeutic derivatives in gynecological oncology. |
| first_indexed | 2024-03-09T19:51:01Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-09T19:51:01Z |
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| spelling | doaj.art-35c9e64a074c4a178cccc242b9d8d5292023-11-24T01:09:17ZengMDPI AGMedicina1010-660X1648-91442022-09-015810133010.3390/medicina58101330Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical PracticeDanilo D. Obradović0Nataša M. Milić1Nenad Miladinović2Lana McClements3Dejan M. Oprić4Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaInstitute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Pathology, Clinical Hospital Centre Zemun, 11000 Belgrade, SerbiaFaculty of Science, School of Life Sciences, University of Technology Sydney, Sydney, NSW 2007, AustraliaInstitute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia<i>Background and Objectives</i>: FK506 binding protein like (FKBPL) is a member of the immunophilin family, with anti-angiogenic effects capable of inhibiting the migration of endothelial cells and blood vessel formation. Its role as an inhibitor of tumor growth and angiogenesis has previously been shown in studies with breast and ovarian cancer. The role of FKBPL in angiogenesis, growth, and carcinogenesis of endometrioid endometrial carcinoma (EEC) is still largely unknown. The aim of this study was to examine the expression of FKBPL in EEC and benign endometrial hyperplasia (BEH) and its correlation with the expression of vascular endothelial factor-A (VEGF-A) and estrogen receptor alpha (ERα). <i>Materials and Methods</i>: Specimens from 89 patients with EEC and 40 patients with BEH, as well as histological, clinical, and demographic data, were obtained from the Clinical Hospital Centre Zemun, Belgrade, Serbia over a 10-year period (2010–2020). Immunohistochemical staining of the tissue was performed for FKBPL, VEGF-A, and ERα. Slides were analyzed blind by two pathologists, who measured the intensity of FKBPL and VEGF-A expression and used the Allred score to determine the level of ERα expression. <i>Results</i>: Immunohistochemical analysis showed moderate to high intensity of FKBPL expression in 97.5% (<i>n</i> = 39) of samples of BEH, and low or no expression in 93.3% (<i>n</i> = 83) of cases of EEC. FKBPL staining showed a high positive predictive value (98.8%) and a high negative predictive value for malignant diagnosis (86.7%). The difference in FKBPL expression between EEC and BEH was statistically significant (<i>p</i> < 0.001), showing a decrease in intensity and loss of expression in malignant tissues of the endometrium. FKBPL expression was positively correlated with ERα expression (intensity, percentage and high Allred score values) and negatively correlated with the expression of VEGF-A (<i>p</i> < 0.05 for all). <i>Conclusions</i>: FKBPL protein expression demonstrated a significant decrease in FKBPL in EEC in comparison to BEH tissue, with a high predictive value for malignancy. FKBPL might be emerging as a significant protein with antiangiogenic and antineoplastic effects, showing great promise for the diagnostic and therapeutic applications of its therapeutic derivatives in gynecological oncology.https://www.mdpi.com/1648-9144/58/10/1330FKBPLendometrioid endometrial carcinomaangiogenesisVEGF-Aestrogen receptor alpha |
| spellingShingle | Danilo D. Obradović Nataša M. Milić Nenad Miladinović Lana McClements Dejan M. Oprić Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice Medicina FKBPL endometrioid endometrial carcinoma angiogenesis VEGF-A estrogen receptor alpha |
| title | Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice |
| title_full | Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice |
| title_fullStr | Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice |
| title_full_unstemmed | Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice |
| title_short | Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice |
| title_sort | loss of expression of antiangiogenic protein fkbpl in endometrioid endometrial carcinoma implications for clinical practice |
| topic | FKBPL endometrioid endometrial carcinoma angiogenesis VEGF-A estrogen receptor alpha |
| url | https://www.mdpi.com/1648-9144/58/10/1330 |
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