Zur Rolle von EZH2 in neuroendokrinen Neoplasien

by Gabi Bittner née Zimmermann
Doctoral thesis
Date of Examination:2024-12-19
Date of issue:2024-11-29
Advisor:Prof. Dr. Philipp Ströbel
Referee:Prof. Dr. Philipp Ströbel
Referee:PD Dr. Achim Rittmeyer
Persistent Address: http://dx.doi.org/10.53846/goediss-10858

 

 

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Abstract

English

Neuroendocrine neoplasms are rare neoplasms with an increasing incidence, primarily occurring in the gastroenteropancreatic region and the lungs. They are classified into the prognostically more favorable NET and the less favorable NEC, with a particular need for precise differentiation in the highly proliferative NEN G3 due to differing therapeutic requirements. Clinical and morphological characteristics, as well as immunohistochemical and molecular markers, aid in this distinction. At present, a reliable differentiation based on these features is not possible, indicating the need for additional markers. EZH2 is known as a prognostic marker in various tumor types. This study investigated the role of EZH2 in 219 GEP-NEN and P-NEN through immunohistochemistry, evaluating its association with clinical behavior and prognosis. The findings showed very low EZH2 expression in NEN G1 and NEN G2, and a highly dichotomous EZH2 expression in NEN G3. In NEN G3, cases with high EZH2 expression demonstrated significantly poorer survival compared to those with low EZH2 expression. High EZH2 levels were generally associated with NEC markers, while low EZH2 levels were linked to NET G3 markers. The markers used to differentiate NEC from NET G3 showed no prognostic relevance, either individually or in combination. Furthermore, there was no correlation between EZH2 expression and PRC2 members EED, SUZ12, and EZH1, or the activity marker H3K27me3. This suggests that EZH2 acts independently of the PRC2 complex in NEN. In summary, EZH2 is highly expressed in highly proliferative NEC and indicated a poorer prognosis. EZH2 proved to be a reliable biomarker in GEP-NEN and P-NEN for distinguishing NEC from NET G3 and operates independently of PRC2.
Keywords: neuroendocrine tumors, neuroendocrine neoplasm, pathology, EZH2, chromogranin A, G3
Schlagwörter: Neuroendokrine Tumore, Neuroendokrine Neoplasie, EZH2, Pathologie, G3