Author(s): Tzao, C (Tzao, Ching); Tung, HJ (Tung, Ho-Jui); Jin, JS (Jin, Jong-Shiaw); Sun, GH (Sun, Guang-Huan); Hsu, HS (Hsu, Han-Shui); Chen, BH (Chen, Ban-Hen); Yu, CP (Yu, Cheng-Ping); Lee, SC (Lee, Shih-Chun)
Title: Prognostic significance of global histone modifications in resected squamous cell carcinoma of the esophagus
Source: MODERN PATHOLOGY, 22 (2): 252-260 FEB 2009 Language: English
Document Type: Article
Author Keywords: histone modification; prognosis; esophageal squamous cell carcinoma KeyWords Plus: PROSTATE-CANCER; LUNG-CANCER; METHYLATION; LYSINE-27;
EZH2; RECURRENCE; MARKERS; BREAST; H3
Abstract: Patterns of global histone modifications have been recently suggested as outcome predictors in cancer patients. To date, there has been no report on the prognostic significance of global histone modifications in esophageal squamous cell carcinoma. We investigated the role of global histone modification as outcome predictor in patients undergoing
esophagectomy for esophageal squamous cell carcinoma. A retrospective clinicopathologic analysis was undertaken of 97 patients with esophageal squamous cell carcinoma who recovered from esophagectomy. Immunohistochemical expression of five histone modification markers, acetylated histone 3 lysine 18 (H3K18Ac), acetylated histone 4 lysine 12 (H4K12Ac), dimethylated histone 4 arginine 3 (H4R3diMe), dimethylated histone 3 lysine 4 (H3 K4diMe), and trimethylated histone 3 lysine 27 (H3K27triMe) was assessed in paraffin-embedded tumor samples. Results were analyzed in relation to patients' clinicopathologic parameters. There was a positive relationship between tumor differentiation and H3K18Ac (P < 0.001), H4R3diMe (P = 0.003), and H3K27triMe (P < 0.001). Expression of H3K27triMe correlated positively with nodal (N) status (P = 0.012) and stage (P = 0.025). Univariate analysis showed that better survival in patients with low expression of H3K18Ac (P = 0.038) and H3K27triMe (P = 0.003).
Multivariate analysis showed that nodal status, metastasis status (M), and expression of H3K27triMe predicted survival independently (P < 0.001, P = 0.016, and 0.048, respectively).
Low expression of H3K18Ac and H3K27triMe correlated with better prognosis of patients with esophageal squamous cell carcinoma, especially for those of early stages. We hypothesize that expression of H3K27triMe may be considered as a significant survival predictor for patients with esophageal squamous cell carcinoma.
Addresses: [Tzao, Ching; Chen, Ban-Hen; Lee, Shih-Chun] Triserv Gen Hosp, Natl Def Med Ctr, Div Thorac Surg, Taipei 114, Taiwan; [Tung, Ho-Jui] Asia Univ, Coll Hlth Sci, Dept Healthcare Adm, Taichung, Taiwan; [Jin, Jong-Shiaw; Yu, Cheng-Ping] Triserv Gen Hosp, Natl Def Med Ctr, Dept Pathol, Taipei 114, Taiwan; [Sun, Guang-Huan] Triserv Gen Hosp, Natl Def Med Ctr, Dept Surg, Taipei 114, Taiwan; [Hsu, Han-Shui] Vet Gen Hosp, Div Thorac
Surg, Taipei, Taiwan
Reprint Address: Tzao, C, Triserv Gen Hosp, Natl Def Med Ctr, Div Thorac Surg, 325,Sect 2,Cheng Gong Rd, Taipei 114, Taiwan.
E-mail Address: [email protected]
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Publisher: NATURE PUBLISHING GROUP
Publisher Address: 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
ISSN: 0893-3952
DOI: 10.1038/modpathol.2008.172
29-char Source Abbrev.: MODERN PATHOL ISO Source Abbrev.: Mod. Pathol.
Source Item Page Count: 9 Subject Category: Pathology ISI Document Delivery No.: 404WA
