Expression of estrogen receptor α and β in esophageal squamous cell carcinoma

Dong,Jing; Jiang,Shi-Wen; Niu,Yanru; Chen,Ling; Liu,Shuyan; Ma,Tianzhong; Chen,Xiancai; Xu,Liyan; Su,Zhongjing; Chen,Haibin

doi:10.3892/or.2013.2770

Expression of estrogen receptor α and β in esophageal squamous cell carcinoma

Authors:
- Jing Dong
- Shi-Wen Jiang
- Yanru Niu
- Ling Chen
- Shuyan Liu
- Tianzhong Ma
- Xiancai Chen
- Liyan Xu
- Zhongjing Su
- Haibin Chen
View Affiliations

Affiliations: Department of Histology and Embryology, Shantou University Medical College, Shantou, Guangdong, P.R. China, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong, P.R. China, Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong, P.R. China
Published online on: October 1, 2013 https://doi.org/10.3892/or.2013.2770
Pages: 2771-2776

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Estrogen receptors (ERs) are frequently expressed in human tumor tissues. There have been several studies concerning ER expression in esophageal cancers, yet the results are inconsistent, and the prognostic value of the receptors remains unclear. In the present study, we investigated the expression of ER protein and its correlation with clinical features of esophageal squamous cell carcinoma (ESCC) patients. Immunohistochemical staining for the ERs was carried out on paraffin-embedded primary tumor tissue sections from 89 patients with ESCC. Quantitative analyses were performed to determine the prognostic value of the expression of ERs, and Pearson's correlation was used to examine the relationship between ERα and ERβ expression levels. Our results showed that ERα immunoreactivity was significantly lower in ESCC than that in the non-neoplastic epithelium (P=0.0445), whereas the ERβ status was much stronger in ESCC than that in the non-neoplastic epithelium (P=0.0243). A significant inverse correlation was observed between ERα expression and depth of tumor invasion (P=0.0426). Correlation analysis revealed a statistically significant inverse correlation between the expression of ERα and ERβ in ESCC (r=-0.2902, P=0.0058). Kaplan-Meier survival analysis showed that the patients with ERα expression (21/89) had a better outcome than patients without ERα expression (P=0.0280), whereas patients with high ERβ immunoreactivity (44/89) were significantly associated with worse survival (P=0.0366). In conclusion, ERα and ERβ levels were inversely correlated, and the downregulation of ERα and upregulation of ERβ may indicate unfavorable prognosis of ESCC.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
2	Sugimachi K, Matsuoka H, Matsufuji H, Maekawa S, Kai H and Okudaira Y: Survival rates of women with carcinoma of the esophagus exceed those of men. Surg Gynecol Obstet. 164:541–544. 1987.PubMed/NCBI
3	Matsuoka H, Sugimachi K, Ueo H, Kuwano H, Nakano S and Nakayama M: Sex hormone response of a newly established squamous cell line derived from clinical esophageal carcinoma. Cancer Res. 47:4134–4140. 1987.PubMed/NCBI
4	Ueo H, Matsuoka H, Sugimachi K, Kuwano H, Mori M and Akiyoshi T: Inhibitory effects of estrogen on the growth of a human esophageal carcinoma cell line. Cancer Res. 50:7212–7215. 1990.PubMed/NCBI
5	Derakhshan MH, Liptrot S, Paul J, Brown IL, Morrison D and McColl KE: Oesophageal and gastric intestinal-type adenocarcinomas show the same male predominance due to a 17 year delayed development in females. Gut. 58:16–23. 2009.PubMed/NCBI
6	Niikawa H, Suzuki T, Miki Y, et al: Intratumoral estrogens and estrogen receptors in human non-small cell lung carcinoma. Clin Cancer Res. 14:4417–4426. 2008. View Article : Google Scholar : PubMed/NCBI
7	Mauro LV, Dalurzo M, Carlini MJ, et al: Estrogen receptor β and epidermal growth factor receptor as early-stage prognostic biomarkers of non-small cell lung cancer. Oncol Rep. 24:1331–1338. 2010.
8	Teng J, Wang ZY, Jarrard DF and Bjorling DE: Roles of estrogen receptor alpha and beta in modulating urothelial cell proliferation. Endocr Relat Cancer. 15:351–364. 2008. View Article : Google Scholar : PubMed/NCBI
9	Rath-Wolfson L, Purim O, Ram E, Morgenstern S, Koren R and Brenner B: Expression of estrogen receptor β1 in colorectal cancer: Correlation with clinicopathological variables. Oncol Rep. 27:2017–2022. 2012.
10	Hogan AM, Collins D, Baird AW and Winter DC: Estrogen and gastrointestinal malignancy. Mol Cell Endocrinol. 307:19–24. 2009. View Article : Google Scholar : PubMed/NCBI
11	Woo IS, Park MJ, Choi SW, et al: Loss of estrogen receptor-α expression is associated with hypermethylation near its ATG start codon in gastric cancer cell lines. Oncol Rep. 11:617–622. 2004.
12	Peng B, Lu B, Leygue E and Murphy LC: Putative functional characteristics of human estrogen receptor-beta isoforms. J Mol Endocrinol. 30:13–29. 2003. View Article : Google Scholar : PubMed/NCBI
13	Utsumi Y, Nakamura T, Nagasue N, Kubota H and Morikawa S: Role of estrogen receptors in the growth of human esophageal carcinoma. Cancer. 64:88–93. 1989. View Article : Google Scholar : PubMed/NCBI
14	Utsumi Y, Nakamura T, Nagasue N, Kubota H, Harada T and Morikawa S: Effect of 17 beta-estradiol on the growth of an estrogen receptor-positive human esophageal carcinoma cell line. Cancer. 67:2284–2289. 1991. View Article : Google Scholar : PubMed/NCBI
15	Nozoe T, Oyama T, Takenoyama M, Hanagiri T, Sugio K and Yasumoto K: Significance of immunohistochemical expression of estrogen receptors alpha and beta in squamous cell carcinoma of the esophagus. Clin Cancer Res. 13:4046–4050. 2007. View Article : Google Scholar : PubMed/NCBI
16	Kalayarasan R, Ananthakrishnan N, Kate V and Basu D: Estrogen and progesterone receptors in esophageal carcinoma. Dis Esophagus. 21:298–303. 2008. View Article : Google Scholar : PubMed/NCBI
17	Wang QM, Yuan L, Qi YJ, Ma ZY and Wang LD: Estrogen analogues: promising target for prevention and treatment of esophageal squamous cell carcinoma in high risk areas. Med Sci Monit. 16:HY19–HY22. 2010.PubMed/NCBI
18	Zuguchi M, Miki Y, Onodera Y, et al: Estrogen receptor alpha and beta in esophageal squamous cell carcinoma. Cancer Sci. 103:1348–1355. 2012. View Article : Google Scholar : PubMed/NCBI
19	Yang H, Sukocheva OA, Hussey DJ and Watson DI: Estrogen, male dominance and esophageal adenocarcinoma: is there a link? World J Gastroenterol. 18:393–400. 2012. View Article : Google Scholar : PubMed/NCBI
20	Wang QM, Qi YJ, Jiang Q, Ma YF and Wang LD: Relevance of serum estradiol and estrogen receptor beta expression from a high-incidence area for esophageal squamous cell carcinoma in China. Med Oncol. 28:188–193. 2011. View Article : Google Scholar : PubMed/NCBI
21	McDonnell DP and Norris JD: Connections and regulation of the human estrogen receptor. Science. 296:1642–1644. 2002. View Article : Google Scholar : PubMed/NCBI
22	Kawai H, Ishii A, Washiya K, et al: Estrogen receptor alpha and beta are prognostic factors in non-small cell lung cancer. Clin Cancer Res. 11:5084–5089. 2005. View Article : Google Scholar : PubMed/NCBI
23	Liu S, Zhu N and Chen H: Expression patterns of human DAB2IP protein in fetal tissues. Biotech Histochem. 87:350–359. 2012. View Article : Google Scholar : PubMed/NCBI
24	Bredfeldt TG, Greathouse KL, Safe SH, Hung MC, Bedford MT and Walker CL: Xenoestrogen-induced regulation of EZH2 and histone methylation via estrogen receptor signaling to PI3K/AKT. Mol Endocrinol. 24:993–1006. 2010. View Article : Google Scholar : PubMed/NCBI
25	He LR, Liu MZ, Li BK, et al: Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma. BMC Cancer. 9:4612009. View Article : Google Scholar : PubMed/NCBI
26	He LR, Liu MZ, Li BK, et al: High expression of EZH2 is associated with tumor aggressiveness and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy. Int J Cancer. 127:138–147. 2010. View Article : Google Scholar : PubMed/NCBI
27	Zhao G, Nie Y, Lv M, et al: ERbeta-mediated estradiol enhances epithelial mesenchymal transition of lung adenocarcinoma through increasing transcription of midkine. Mol Endocrinol. 26:1304–1315. 2012. View Article : Google Scholar
28	Zhao G, Zhao S, Wang T, Zhang S, Lu K, Yu L and Hou Y: Estrogen receptor beta signaling regulates the progression of Chinese non-small cell lung cancer. J Steroid Biochem Mol Biol. 124:47–57. 2011. View Article : Google Scholar : PubMed/NCBI