Background: EZH2 is a histone lysine methyltransferase that is a member of the polycomb group protein family. EZH2 plays an important role in the epigenetic maintenance of H3K27 trimethylation (H3K27me3). Abnormal EZH2 expression has been associated with various cancers. We examined the expression of EZH2 and H3K27me3 to determine their roles in thyroid cancer progression. Design: Anaplastic thyroid carcinomas (ATC, n=35), poorly differentiated thyroid carcinomas (PDTC, n=21), papillary thyroid carcinomas (PTC, n=28), follicular variant of papillary thyroid carcinomas (FVPTC, n=29), follicular thyroid carcinomas (FTC, n=28), follicular adenomas (FA, n=31) and normal thyroids (NT, n=10) on a tissue microarray (TMA) were analyzed by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded tissues. Antibodies to EZH2 (Novus, 1:100) and H3K27me3 (Cell Signaling, 1:200) were used. IHC was scored based on the intensity and percentage of nuclear staining. Survival analysis was performed using the statistical computing software R. Results: Both EZH2 and H3K27me3 showed strong nuclear staining. The highest level of EZH2 expression was observed in ATC (97%) followed by PDTC (90%). Levels were lower in FA (71%), FTC (64%), PTC (79%) and FVPTC (79%). EZH2 expression was significantly higher in ATC than in well-differentiated carcinomas (P<0.04). H3K27me3 expression was high in both benign and malignant thyroid tumors as well as in NT. H3K27me3 expression was not significantly different in higher-grade tumors compared to well-differentiated carcinomas and FA. The carcinoma types expressing the highest levels of EZH2 (ATC and PDTC) had worse prognoses than the carcinoma types with lower expression (P<0.001). Conclusions: EZH2 is expressed in thyroid malignancies, and its expression correlates with higher-grade tumors. EZH2 effects may also include H3K27me3-independent mechanisms. Our findings suggest that EZH2 may play an important role in thyroid tumor progression.

Enhancer of Zeste Homolog 2 (EZH2) and Global H3K27 Trimethylation Expression During Progression of Thyroid Cancer

ASIOLI, SOFIA;RIGHI, ALBERTO;
2015

Abstract

Background: EZH2 is a histone lysine methyltransferase that is a member of the polycomb group protein family. EZH2 plays an important role in the epigenetic maintenance of H3K27 trimethylation (H3K27me3). Abnormal EZH2 expression has been associated with various cancers. We examined the expression of EZH2 and H3K27me3 to determine their roles in thyroid cancer progression. Design: Anaplastic thyroid carcinomas (ATC, n=35), poorly differentiated thyroid carcinomas (PDTC, n=21), papillary thyroid carcinomas (PTC, n=28), follicular variant of papillary thyroid carcinomas (FVPTC, n=29), follicular thyroid carcinomas (FTC, n=28), follicular adenomas (FA, n=31) and normal thyroids (NT, n=10) on a tissue microarray (TMA) were analyzed by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded tissues. Antibodies to EZH2 (Novus, 1:100) and H3K27me3 (Cell Signaling, 1:200) were used. IHC was scored based on the intensity and percentage of nuclear staining. Survival analysis was performed using the statistical computing software R. Results: Both EZH2 and H3K27me3 showed strong nuclear staining. The highest level of EZH2 expression was observed in ATC (97%) followed by PDTC (90%). Levels were lower in FA (71%), FTC (64%), PTC (79%) and FVPTC (79%). EZH2 expression was significantly higher in ATC than in well-differentiated carcinomas (P<0.04). H3K27me3 expression was high in both benign and malignant thyroid tumors as well as in NT. H3K27me3 expression was not significantly different in higher-grade tumors compared to well-differentiated carcinomas and FA. The carcinoma types expressing the highest levels of EZH2 (ATC and PDTC) had worse prognoses than the carcinoma types with lower expression (P<0.001). Conclusions: EZH2 is expressed in thyroid malignancies, and its expression correlates with higher-grade tumors. EZH2 effects may also include H3K27me3-independent mechanisms. Our findings suggest that EZH2 may play an important role in thyroid tumor progression.
LABORATORY INVESTIGATION
Sundling, Kaitlin; Montemayor-Garcia, Celina; Hardin, Heather; Buehler, Darya; Asioli, Sofia; Righi, Alberto; Lloyd, Ricardo .
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/515071
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