Expressions of ERβ and PTEN in human breast cancer tissue and clinical significance

doi:10.3877/cma.j.issn.1674-0807.2016.05.005

Abstract

Abstract:

Objective

To evaluate the expressions of ERβ and PTEN in human breast cancer tissue,and their correlation with clinicopathological characteristics.

Methods

We retrospectively examined ERβ and PTEN expressions in breast cancer specimens from 110 patients treated in Department of Breast Surgery,Southwest Hospital, Third Military Medical University in 2008-2009 by immunohistochemistry. χ² test was used to analyze the relationship between the expressions of two factors and the clinicopathological characteristics, Spearman method was used to analyze the correlation between ERβ and PTEN, and Kaplan-Meier survival analysis was used to analyze the relationship between their expressions and patients' survival.

Results

The positive expression rate of ERβ was 62.7%(69/110)and the positive expression rate of PTEN was 59.1%(65/110),indicating a positive correlation between ERβ and PTEN (r=0.276,P=0.003). ERβ expression was associated with TNM stage (χ²=11.766, P=0.003) and lymph node metastasis (χ²=9.919,P=0.007); PTEN expression was also correlated with TNM stage (χ² =9.014,P=0.011) and lymph node metastasis (χ²=12.201,P=0.002). The patients were followed up for 8-70 months, median 39 months.Survival analysis showed that ERβ positive patients exhibited a better 5-year DFS than those with ERβ negative did (χ² =7.707,P=0.005), and PTEN positive patients had a better 5-year DFS compared with PTEN negative patients (χ²=7.057,P=0.008). There were 48 patients with ERβ positive and PTEN negative,17 patients with ERβ negative and PTEN positive, 21 patients with ERβ positive and PTEN-positive and 24 patients with ERβ-negative and PTEN-negative. The above-mentioned 4 groups showed a significant difference in DFS(χ² = 16.790,P＜0.001),DFS in patients with ERβ negative and PTEN negative was significantly lower than that in other 3 groups(χ²=4.162,P=0.041;χ²=4.835,P=0.028;χ²=12.640,P＜0.001).

Conclusion

The breast cancer patients with negative ERβ and PTEN expressions have a poor prognosis, so the two factors can be used as new molecular markers for evaluation of prognosis.

Key words: Breast neoplasms, Estrogen receptor β, PTEN phosphohydrolase, Prognosis

Zihan Sun, Qinwen Pan, Long Yuan, Hongyi Wei. Expressions of ERβ and PTEN in human breast cancer tissue and clinical significance[J]. Chinese Journal of Breast Disease(Electronic Edition), 2016, 10(05): 276-281.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhrxbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0807.2016.05.005

https://zhrxbzz.cma-cmc.com.cn/EN/Y2016/V10/I05/276

Figures/Tables 5

References 21

[1]	Holst F. Estrogen receptor alpha gene amplification in breast cancer:25 years of debate[J]. World J Clin Oncol,2016,7(2):160-173.
[2]	Ogawa S, Inoue S, Watanabe T, et al. The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitro[J]. Biochem Biophys Res Commun,1998,243(1):122-126.
[3]	Leung YK, Mak P, Hassan S, et al. Estrogen receptor (ER)-beta isoforms:a key to understanding ER-beta signaling[J]. Proc Natl Acad Sci U S A,2006,103(35):13 162-13 167.
[4]	Chen L, Qiu J, Yang C, et al. Identification of a novel estrogen receptor beta1 binding partner,inhibitor of differentiation-1,and role of ERbeta1 in human breast cancer cells [J]. Cancer Lett, 2009,278(2):210-219.
[5]	Guo L, Zhang Y, Zhang W, et al. Correlation between estrogen receptor beta expression and the curative effect of endocrine therapy in breast cancer patients[J]. Exp Ther Med,2014,7(6):1568-1572.
[6]	Lindberg K, Helguero LA, Omoto Y, et al. Estrogen receptor beta represses Akt signaling in breast cancer cells via downregulation of HER2/HER3 and upregulation of PTEN: implications for tamoxifen sensitivity[J]. Breast Cancer Res,2011,13(2):R43.
[7]	Ren X, Yuan L, Shen S, et al. c-Met and ERbeta expression differences in basal-like and non-basal-like triple-negative breast cancer[J]. Tumour Biol,2016,37(8):11 385-11 395.
[8]	Sakr RA, Barbashina V, Morrogh M, et al. Protocol for PTEN expression by immunohistochemistry in formalin-fixed paraffinembedded human breast carcinoma[J]. Appl Immunohistochem Mol Morphol,2010,18(4):371-374.
[9]	Madeira M,Mattar A,Logullo AF,et al. Estrogen receptor alpha/beta ratio and estrogen receptor beta as predictors of endocrine therapy responsiveness-a randomized neoadjuvant trial comparison between anastrozole and tamoxifen for the treatment of postmenopausal breast cancer[J]. BMC Cancer,2013,13:425.
[10]	Liu J, Guo H, Mao K, et al. Impact of estrogen receptor-beta expression on breast cancer prognosis: a meta-analysis[J]. Breast Cancer Res Treat,2016,156(1):149-162.
[11]	Chang HG, Kim SJ, Chung KW, et al. Tamoxifen-resistant breast cancers show less frequent methylation of the estrogen receptor beta but not the estrogen receptor alpha gene[J]. J Mol Med(Berl), 2005,83(2):132-139.
[12]	Guo L, Meng J, Yilamu D, et al. Significance of ERbeta expression in different molecular subtypes of breast cancer[J]. Diagn pathol, 2014,9:20.
[13]	Omoto Y, Inoue S, Ogawa S, et al. Clinical value of the wild-type estrogen receptor beta expression in breast cancer[J]. Cancer Lett,2001,163(2):207-212.
[14]	Järvinen TA,Pelto-Huikko M,Holli K,et al. Estrogen receptor beta is coexpressed with ERalpha and PR and associated with nodal status,grade, and proliferation rate in breast cancer[J]. Am J Pathol,2000,156(1):29-35.
[15]	Marotti JD, Collins LC,Hu R,et al. Estrogen receptor-beta expression in invasive breast cancer in relation to molecular phenotype: results from the Nurses' Health Study[J]. Mod Pathol, 2010, 23(2):197-204.
[16]	Thomas C, Gustafsson JA. The different roles of ER subtypes in cancer biology and therapy[J]. Nat Rev Cancer,2011,11(8):597-608.
[17]	Thomas C, Rajapaksa G, Nikolos F, et al. ERbeta1 represses basal breast cancer epithelial to mesenchymal transition by destabilizing EGFR[J].Breast Cancer Res,2012,14(6):R148.
[18]	Honma N, Horii R, Iwase T, et al. Clinical importance of estrogen receptor-beta evaluation in breast cancer patients treated with adjuvant tamoxifen therapy[J]. J Clin Oncol,2008,26(22):3727-3734.
[19]	Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer[J]. Science,1997,275(5308):1943-1947.
[20]	Cotrim CZ, Fabris V, Doria ML, et al. Estrogen receptor beta growthinhibitory effects are repressed through activation of MAPK and PI3K signalling in mammary epithelial and breast cancer cells [ J].Oncogene,2013,32(19):2390-2402.
[21]	Wang J, Zhang C, Chen K, et al. ERbeta1 inversely correlates with PTEN/PI3K/AKT pathway and predicts a favorable prognosis in triplenegative breast cancer[J]. Breast Cancer Res Treat, 2015, 152(2):255-269.

临床病理特征	例数	ERβ(例)		χ²值	P值	PTEN(例)		χ²值	P值
临床病理特征	例数	阴性	阳性	χ²值	P值	阴性	阳性	χ²值	P值
年龄
＜50岁	58	24	34	0.885	0.347	24	34	0.011	0.916
≥50岁	52	17	35	0.885	0.347	21	31	0.011	0.916
临床分期
Ⅰ	49	13	36	11.766	0.003	16	33	9.014	0.011
Ⅱ	50	19	31			20	30
Ⅲ	11	9	2			9	2
肿瘤直径
≤2cm	51	14	37	3.974	0.137	16	35	4.425	0.109
＞2～5cm	53	24	29			25	28
＞5cm	6	3	3			4	2
淋巴结转移
0枚	66	17	49	9.919	0.007	19	47	12.201	0.002
1～3枚	26	13	13			13	13
≥4枚	18	11	7			13	5
ERα
阴性	33	16	17	2.535	0.111	11	22	1.119	0.290
阳性	77	25	52	2.535	0.111	34	43	1.119	0.290
PR
阴性	28	13	15	1.347	0.246	11	17	0.041	0.840
阳性	82	28	54	1.347	0.246	34	48	0.041	0.840
HER-2
阴性	62	20	42	1.528	0.216	29	33	2.022	0.155
阳性	48	21	27	1.528	0.216	16	32	2.022	0.155

临床病理特征	例数	ERβ(例)		χ²值	P值	PTEN(例)		χ²值	P值
临床病理特征	例数	阴性	阳性	χ²值	P值	阴性	阳性	χ²值	P值
年龄
＜50岁	58	24	34	0.885	0.347	24	34	0.011	0.916
≥50岁	52	17	35	0.885	0.347	21	31	0.011	0.916
临床分期
Ⅰ	49	13	36	11.766	0.003	16	33	9.014	0.011
Ⅱ	50	19	31			20	30
Ⅲ	11	9	2			9	2
肿瘤直径
≤2cm	51	14	37	3.974	0.137	16	35	4.425	0.109
＞2～5cm	53	24	29			25	28
＞5cm	6	3	3			4	2
淋巴结转移
0枚	66	17	49	9.919	0.007	19	47	12.201	0.002
1～3枚	26	13	13			13	13
≥4枚	18	11	7			13	5
ERα
阴性	33	16	17	2.535	0.111	11	22	1.119	0.290
阳性	77	25	52	2.535	0.111	34	43	1.119	0.290
PR
阴性	28	13	15	1.347	0.246	11	17	0.041	0.840
阳性	82	28	54	1.347	0.246	34	48	0.041	0.840
HER-2
阴性	62	20	42	1.528	0.216	29	33	2.022	0.155
阳性	48	21	27	1.528	0.216	16	32	2.022	0.155

Please choose a citation manager

Content to export