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Open Access Highly Accessed Research article

Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma

Li-Ru He12, Meng-Zhong Liu12*, Bin-Kui Li1, Hui-Lan Rao1, Yi-Ji Liao1, Xin-Yuan Guan1, Yi-Xin Zeng1 and Dan Xie1*

Author Affiliations

1 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, No 651, Dongfeng Road East, 510060 Guangzhou, China

2 Department of Radiotherapy, Cancer Center, Sun Yat-Sen University, No 651, Dongfeng Road East, 510060 Guangzhou, China

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BMC Cancer 2009, 9:461  doi:10.1186/1471-2407-9-461

Published: 22 December 2009

Abstract

Background

Trimethylation of lysine 27 on histone H3 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that mediates gene silencing. EZH2 is overexpressed and correlates with poor prognosis in many cancers. However, the clinical implication of H3K27me3 in human malignancies has not been well established. We wished to ascertain whether a correlation exists between the expression of H3K27me3 and clinical outcome in a group of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT).

Methods

The method of immunohistochemistry (IHC) was utilized to examine the protein expression of H3K27me3 in 98 pretreatment biopsy specimens of ESCC and in 30 samples of normal esophageal mucosa. The clinical/prognostic significance of H3K27me3 expression was statistically analyzed.

Results

The expression frequency and expression levels of H3K27me3 were significantly higher in ESCCs than in normal tissues. There was a positive correlation between H3K27me3 expression and WHO grade (P = 0.016), tumor size (P = 0.019), T status (P = 0.024), locoregional progression (P = 0.009) and EZH2 expression (P = 0.036). High H3K27me3 expression was associated with poor locoregional progression-free survival (LPFS) (P = 0.010) in ESCC. Further analysis demonstrated that H3K27me3 could stratify patient outcome in T2-3 (P = 0.048), N0 (P = 0.005) and M0 (P = 0.018) stages as well as in CRT effective group (P = 0.022).

Conclusions

Our data suggests that H3K27me3 expression examined by IHC might be useful for stratifying LPFS for different subsets of ESCC patients treated with definitive CRT.