High expression of enhancer of zeste homologue 2 indicates poor prognosis in patients with soft tissue sarcomas

Yamaga, Kensaku; Osaki, Mitsuhiko; Kimura, Kazunori; Shomori, Kohei; Yoshida, Haruhiko; Ito, Hisao

doi:10.3892/mmr_00000004

Cited by 7 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the t(X;18) translocation involving the SSX2 gene has been correlated with better outcomes, no studies have confirmed that it is an independent prognostic factor for SS [3,27,28]. Moreover, necrosis, vascular invasion, high mitotic activity, and high Ki-67 proliferative index are accepted histopathological predictors of the shortened survival [9,13,27]. Our results showed that the patients without necrosis had a significantly higher survival time (p = 0.006).…”

Section: Discussionmentioning

confidence: 62%

“…EZH2 is expressed at high levels in cells exhibiting an embryonic gene expression pattern, and its expression declines with tissue maturation and differentiation. Recent studies have suggested that EZH2 overexpression might be related to aggressive behavior and poor prognosis in various carcinomas, lymphomas, and soft tissue sarcomas [13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Section: Discussionmentioning

confidence: 99%

“…Enhancer of zeste homologue 2 (EZH2) belongs to the polycomb group (PcG) proteins of cell cycle regulators that suppress transcription. An excessive expression of EZH2 is found in various carcinomas, lymphomas, and soft tissue sarcomas, and growing evidence suggests that this overexpression correlates with the aggressiveness and poor clinical outcome of such tumors [13][14][15][16][17][18][19][20][21][22]. However, few studies have investigated the expression of EZH2 in SS [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enhancer of zeste homologue 2 (EZH2) expression in synovial sarcomas as a promising indicator of prognosis

Yalçinkaya

Uğraş

Özgün

et al. 2017

Bosn J of Basic Med Sci

View full text Add to dashboard Cite

Synovial sarcoma (SS) is a type of soft-tissue sarcoma, often linked to poor survival. Although overexpression of enhancer of zeste homologue 2 (EZH2) has been associated with poor prognosis in different tumors, a few studies investigated this link in SS. Here, we analyzed the relationship between EZH2 expression and prognostic factors in SS. We included 29 patients with SS. Immunostaining of EZH2 was performed with (D2C9) XPTM Rabbit mAb antibody, and the results were classified as low EZH2 expression (negative or weak expression) and high EZH2 expression category (moderate or strong expression). Analysis of survival in relation to prognostic factors was performed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. Our sample included 19/29 female and 10/29 male patients, with age range 16-63 years. The tumor diameter ranged from 2 to 15 cm. Necrosis was observed in 15/29 cases. Sixteen cases had >10 mitoses per 50 high-power fields (HPFs). Out of 29 cases, 14 showed low and 15 had high EZH2 expression. Statistically significant results were obtained for the association between the presence of metastasis and necrosis (p = 0.042), high EZH2 expression and distant metastasis (p = 0.018), high EZH2 expression and necrosis (p = 0.016), and high EZH2 expression and the tumor size >5 cm versus tumor size ≤5 cm (p = 0.014). Patients with all of the following: the tumor size ≤5 cm, low EZH2 expression, and without necrosis and distant metastasis had significantly longer survival time. Our results are consistent with previous studies, suggesting that EZH2 overexpression is an indicator of poor prognosis in SS.

show abstract

Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Enhancer of zeste homologue 2 (EZH2) expression in synovial sarcomas as a promising indicator of prognosis

Yalçinkaya

Uğraş

Özgün

et al. 2017

Bosn J of Basic Med Sci

View full text Add to dashboard Cite

show abstract

“…It is well known that repression of E-cadherin by EZH2 is associated with the aggressiveness of many carcinomas, 27 but it is still not clear what kind of other genes are silenced by EZH2 in different tumors, although it seems that SMARCB1 is not affected. To our best knowledge, this is the first report of larger series of EZH2 expression in epithelioid sarcoma although five cases with a 16% labeling index were reported by Yamaga K et al 28 It is possible, although unlikely, that the H3K27me3 mark is present without overexpression of EZH2, which could be assessed by chromatin immunoprecipitation followed by PCR.…”

Section: Discussionmentioning

confidence: 68%

SMARCB1 protein and mRNA loss is not caused by promoter and histone hypermethylation in epithelioid sarcoma

et al. 2013

View full text Add to dashboard Cite

About 10% of epithelioid sarcomas have biallelic mutation of the SMARCB1 (SWI/SNF-related, matrixassociated, actin-dependent regulator of chromatin, subfamily b, member 1) gene resulting in a lack of this nuclear protein. It has been suggested that SMARCB1 may be silenced by epigenetic changes in the remaining 90% of tumors. Thus, we hypothesized that the promoter of SMARCB1 is hypermethylated. We also examined SMARCB1 mRNA level to determine if a post-translational change was possible. Thirty-six cases of epithelioid sarcomas were studied. Immunohistochemistry and mutation analysis of the SMARCB1 gene were performed to select appropriate cases. Methylation status was assessed by methylation-specific PCR. Laser capture microdissection of tumor cells followed by real-time PCR was applied to examine the expression of SMARCB1 mRNA. Of 36 epithelioid sarcomas, 31 (86%) displayed a lack of SMARCB1 nuclear protein. In all, 4 (13%) of 31 SMARCB1-negative cases harbored biallelic deletion while 9 (33%) cases showed single-allelic deletion. One (4%) frameshift deletion of exon 3 and one point mutation of exon 7 were also found. In 16 (59%) cases, both alleles were intact. Altogether, 25/31 (81%) SMARCB1-negative cases had at least one intact allele. None of these cases demonstrated promoter hypermethylation. Low levels of SMARCB1 mRNA were found in all cases with tumor tissue extracted RNA (because of the minimal normal cell contamination) but no mRNA could be detected in laser dissected cases (containing only tumor cells). Enhancer of zeste homolog 2 (EZH2) overexpression was not characteristic of epithelioid sarcoma. Thus, loss of SMARCB1 expression in epithelioid sarcoma is caused neither by DNA hypermethylation nor by post-translational modifications. Most likely it is the microRNA destruction of SMARCB1 mRNA but further investigations are needed to elucidate this issue. Keywords: epithelioid sarcoma; histone methylation; laser capture microdissection; methylation-specific PCR; promoter hypermethylation; SMARCB1The SMARCB1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1; also known as INI1, BAF47 and hSNF5) gene, located on chromosomal position 22q11.23, encodes a core subunit of the SWI/SNF ATP-dependent chromatin remodeling complex. 1 Such observations show these complexes regulate gene expression, at least in part, by inducing a nucleosome conformation that is more approachable to the transcriptional machinery. 2 Recently, inactivation of both alleles of the SMARCB1 gene was identified in the majority of malignant rhabdoid tumors, suggesting that loss-of-function mutations of the gene contributed to the oncogenesis of this type of tumor.

show abstract

“…It is necessary to select the appropriate therapy for patients with STSs due to their different pathobiological behavior and prognostic significance. A number of prognostic or biological markers were studied in STSs and reported to be significant prognostic markers (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of Minichromosome maintenance protein 7 and Geminin expression in patients with 109 soft tissue sarcomas

Hamamoto

Shomori²,

Nosaka³

et al. 2010

Oncology Letters

View full text Add to dashboard Cite

Abstract. Minichromosome maintenance complex (MCM2-7)and Geminin are important in the prevention of DNA re-replication in the cell cycle, and are also prognostic markers for numerous human malignancies. The present study examined Minichromosome maintenance protein 7 (MCM7) and Geminin expression in human soft tissue sarcomas (STSs) to clarify their correlation to the clinicopathological factors. Immunohistochemistry was performed to detect the expression of MCM7, Geminin and Ki-67 on paraffin-embedded sections of 109 STSs. Labeling indices (LIs) of the molecules were evaluated in the tumors. Higher LIs of MCM7, Geminin and Ki-67 were significantly correlated with distant metastasis (P<0.01), histological grade (P<0.01) and poor prognosis (P<0.01), respectively. LIs of MCM7 and Geminin were significantly correlated with Ki-67 LIs, (MCM7/Ki-67: rs=0.745, P<0.01 and Geminin/Ki-67: rs=0.604, P<0.01). Multivariate analyses showed that the higher LIs of Geminin, but not MCM7 and Ki-67, were shown to be an independent factor of poorer prognosis (relative risk 2.72, P=0.013). The immunohistochemical expression of MCM7 and Geminin may be novel and useful markers for evaluating the prognosis in patients with human STS.

show abstract

High expression of enhancer of zeste homologue 2 indicates poor prognosis in patients with soft tissue sarcomas

Cited by 7 publications

References 29 publications

Enhancer of zeste homologue 2 (EZH2) expression in synovial sarcomas as a promising indicator of prognosis

Enhancer of zeste homologue 2 (EZH2) expression in synovial sarcomas as a promising indicator of prognosis

SMARCB1 protein and mRNA loss is not caused by promoter and histone hypermethylation in epithelioid sarcoma

Prognostic significance of Minichromosome maintenance protein 7 and Geminin expression in patients with 109 soft tissue sarcomas

Contact Info

Product

Resources

About