Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor Prognosis
Tumor grading is a robust prognostic predictor in patients with neuroendocrine neoplasms (NEN) and guides therapy, especially in tumors with high proliferation. NEN can be separated into well-differentiated and poorly differentiated types. The more aggressive NEN have been further separated into neu...
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MDPI AG
2022-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/12/2828 |
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| author | Sebastian C. B. Bremer Gabi Bittner Omar Elakad Helen Dinter Jochen Gaedcke Alexander O. König Ahmad Amanzada Volker Ellenrieder Alexander Freiherr von Hammerstein-Equord Philipp Ströbel Hanibal Bohnenberger |
| author_facet | Sebastian C. B. Bremer Gabi Bittner Omar Elakad Helen Dinter Jochen Gaedcke Alexander O. König Ahmad Amanzada Volker Ellenrieder Alexander Freiherr von Hammerstein-Equord Philipp Ströbel Hanibal Bohnenberger |
| author_sort | Sebastian C. B. Bremer |
| collection | DOAJ |
| description | Tumor grading is a robust prognostic predictor in patients with neuroendocrine neoplasms (NEN) and guides therapy, especially in tumors with high proliferation. NEN can be separated into well-differentiated and poorly differentiated types. The more aggressive NEN have been further separated into neuroendocrine tumors (NET G3) with a better prognosis and neuroendocrine carcinomas (NEC) with a worse prognosis. Despite this distinction’s tremendous clinical and therapeutic relevance, optimal diagnostic biomarkers are still lacking. In this study, we analyzed the protein expression and prognostic impact of Enhancer of Zeste Homolog 2 (EZH2) by immunohistochemistry in 219 tissue samples of gastroenteropancreatic (GEP-NEN) and pulmonary NEN (P-NEN). EZH2 was almost exclusively expressed in NEN with a proliferation rate above 20% (G3), while all low-grade tumors were nearly negative. Among high-grade NEN, 65% showed high and 35% low expression of EZH2. In this group, the high expression of EZH2 was significantly associated with poor overall survival and NEC histology. Interestingly, EZH2 seems to act independently of Polycomb Repressive Complex 2 (PRC2) in NEN. In conclusion, we propose EZH2 as a robust biomarker for distinguishing between NET G3 and NEC among gastroenteropancreatic and pulmonary NEN. |
| first_indexed | 2024-03-10T00:13:40Z |
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| id | doaj.art-11b399ef077b4cd08f4817e1f7a18f39 |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:13:40Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-11b399ef077b4cd08f4817e1f7a18f392023-11-23T15:54:52ZengMDPI AGCancers2072-66942022-06-011412282810.3390/cancers14122828Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor PrognosisSebastian C. B. Bremer0Gabi Bittner1Omar Elakad2Helen Dinter3Jochen Gaedcke4Alexander O. König5Ahmad Amanzada6Volker Ellenrieder7Alexander Freiherr von Hammerstein-Equord8Philipp Ströbel9Hanibal Bohnenberger10Clinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyInstitute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyInstitute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyInstitute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyClinic for General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyClinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyClinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyClinic for Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyClinic for Cardiac, Thoracic and Vascular Surgery, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyInstitute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyInstitute of Pathology, University Medical Center Goettingen, Georg-August-University, 37075 Goettingen, GermanyTumor grading is a robust prognostic predictor in patients with neuroendocrine neoplasms (NEN) and guides therapy, especially in tumors with high proliferation. NEN can be separated into well-differentiated and poorly differentiated types. The more aggressive NEN have been further separated into neuroendocrine tumors (NET G3) with a better prognosis and neuroendocrine carcinomas (NEC) with a worse prognosis. Despite this distinction’s tremendous clinical and therapeutic relevance, optimal diagnostic biomarkers are still lacking. In this study, we analyzed the protein expression and prognostic impact of Enhancer of Zeste Homolog 2 (EZH2) by immunohistochemistry in 219 tissue samples of gastroenteropancreatic (GEP-NEN) and pulmonary NEN (P-NEN). EZH2 was almost exclusively expressed in NEN with a proliferation rate above 20% (G3), while all low-grade tumors were nearly negative. Among high-grade NEN, 65% showed high and 35% low expression of EZH2. In this group, the high expression of EZH2 was significantly associated with poor overall survival and NEC histology. Interestingly, EZH2 seems to act independently of Polycomb Repressive Complex 2 (PRC2) in NEN. In conclusion, we propose EZH2 as a robust biomarker for distinguishing between NET G3 and NEC among gastroenteropancreatic and pulmonary NEN.https://www.mdpi.com/2072-6694/14/12/2828neuroendocrine neoplasiaEZH2survival |
| spellingShingle | Sebastian C. B. Bremer Gabi Bittner Omar Elakad Helen Dinter Jochen Gaedcke Alexander O. König Ahmad Amanzada Volker Ellenrieder Alexander Freiherr von Hammerstein-Equord Philipp Ströbel Hanibal Bohnenberger Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor Prognosis Cancers neuroendocrine neoplasia EZH2 survival |
| title | Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor Prognosis |
| title_full | Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor Prognosis |
| title_fullStr | Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor Prognosis |
| title_full_unstemmed | Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor Prognosis |
| title_short | Enhancer of Zeste Homolog 2 (EZH2) Is a Marker of High-Grade Neuroendocrine Neoplasia in Gastroenteropancreatic and Pulmonary Tract and Predicts Poor Prognosis |
| title_sort | enhancer of zeste homolog 2 ezh2 is a marker of high grade neuroendocrine neoplasia in gastroenteropancreatic and pulmonary tract and predicts poor prognosis |
| topic | neuroendocrine neoplasia EZH2 survival |
| url | https://www.mdpi.com/2072-6694/14/12/2828 |
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