Expression profile and prognostic role of sex hormone receptors in gastric cancer

BMC Cancer

Lu Gan¹  Jian He¹  Xia Zhang¹  Yong-Jie Zhang¹  Guan-Zhen Yu¹  Ying Chen²  Jun Pan¹  Jie-Jun Wang¹  Xi Wang¹ 

[1] Department of Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China

[2] Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China

关键词: Prognosis;    Androgen receptor;    Progesterone receptor;    Estrogen receptor beta;    Estrogen receptor alpha;    Gastric cancer;   

Others  :  1080045
DOI  :  10.1186/1471-2407-12-566

 received in 2012-08-08, accepted in 2012-11-28,  发布年份 2012

【 摘 要 】

Background

Increasing interest has been devoted to the expression and possible role of sex hormone receptors in gastric cancer, but most of these findings are controversial. In the present study, the expression profile of sex hormone receptors in gastric cancer and their clinicopathological and prognostic value were determined in a large Chinese cohort.

Methods

The mRNA and protein expression of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), progesterone receptor (PR), and androgen receptor (AR) in primary gastric tumors and corresponding adjacent normal tissues from 60 and 866 Chinese gastric cancer patients was detected by real-time quantitative PCR and immunohistochemistry method, respectively. The expression profile of the four receptors was compared and their associations with clinicopathological characteristics were assessed by using Chi-square test. The prognostic value of the four receptors in gastric cancer was evaluated by using univariate and multivariate Cox regression analysis.

Results

The presence of ERα, ERβ, PR, and AR in both gastric tumors and normal tissues was confirmed but their expression levels were extremely low except for the predominance of ERβ. The four receptors were expressed independently and showed a decreased expression pattern in gastric tumors compared to adjacent normal tissues. The positive expression of the four receptors all correlated with high tumor grade and intestinal type, and ERα and AR were also associated with early TNM stage and thereby a favorable outcome. However, ERα and AR were not independent prognostic factors for gastric cancer when multivariate survival analysis was performed.

Conclusions

Our findings indicate that the sex hormone receptors may be partly involved in gastric carcinogenesis but their clinicopathological and prognostic significance in gastric cancer appears to be limited.

【 授权许可】

   
2012 Gan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Hurvitz SA, Pietras RJ: Rational management of endocrine resistance in breast cancer: a comprehensive review of estrogen receptor biology, treatment options, and future directions. Cancer 2008, 113:2385-2397.
• [2]Ramirez ML, Keane TE, Evans CP: Managing prostate cancer: the role of hormone therapy. Can J Urol 2007, 14(Suppl 1):10-18.
• [3]Hayashi S, Yamaguchi Y: Estrogen signaling pathway and hormonal therapy. Breast Cancer 2008, 15:256-261.
• [4]Osborne CK, Schiff R: Mechanisms of endocrine resistance in breast cancer. Annu Rev Med 2011, 62:233-247.
• [5]Thomas C, Gustafsson JÅ: The different roles of ER subtypes in cancer biology and therapy. Nat Rev Cancer 2011, 11:597-608.
• [6]Chen GG, Zeng Q, Tse GM: Estrogen and its receptors in cancer. Med Res Rev 2008, 28:954-974.
• [7]Ahmad N, Kumar R: Steroid hormone receptors in cancer development: a target for cancer therapeutics. Cancer Lett 2011, 300:1-9.
• [8]Wu CW, Lui WY, P’eng FK, Chi CW: Hormonal therapy for stomach cancer. Med Hypotheses 1992, 39:137-139.
• [9]Tokunaga A, Kojima N, Andoh T, Matsukura N, Yoshiyasu M, Tanaka N, Ohkawa K, Shirota A, Asano G, Hayashi K: Hormone receptors in gastric cancer. Eur J Cancer Clin Oncol 1983, 19:687-689.
• [10]Tokunaga A, Nishi K, Matsukura N, Tanaka N, Onda M, Shirota A, Asano G, Hayashi K: Estrogen and progesterone receptors in gastric cancer. Cancer 1986, 57:1376-1379.
• [11]Yokozaki H, Takekura N, Takanashi A, Tabuchi J, Haruta R, Tahara E: Estrogen receptors in gastric adenocarcinoma: a retrospective immunohistochemical analysis. Virchows Arch A Pathol Anat Histopathol 1988, 413:297-302.
• [12]Wu CW, Chi CW, Chang TJ, Lui WY, P’eng FK: Sex hormone receptors in gastric cancer. Cancer 1990, 65:1396-1400.
• [13]Sica V, Nola E, Contieri E, Bova R, Masucci MT, Medici N, Petrillo A, Weisz A, Molinari AM, Puca GA: Estradiol and progesterone receptors in malignant gastrointestinal tumors. Cancer Res 1984, 44:4670-4674.
• [14]Oshima CT, Wonraht DR, Catarino RM, Mattos D, Forones NM: Estrogen and progesterone receptors in gastric and colorectal cancer. Hepatogastroenterology 1999, 46:3155-3158.
• [15]Wu CW, Chang HM, Kao HL, Lui WY, P’eng FK, Chi CW: The nontransformed progesterone and estrogen receptors in gastric cancer. Gastroenterology 1992, 102:1639-1646.
• [16]Korenaga D, Orita H, Okuyama T, Kinoshita J, Maekawa S, Ikeda T, Sugimachi K: Sex hormone-receptor-negative tumors have a higher proliferative activity than sex hormone-receptor-positive tumors in human adenocarcinomas of the gastrointestinal tract. Surg Today 1998, 28:1007-1014.
• [17]Theodoropoulos GE, Lazaris AC, Panoussopoulos D, Davaris P, Golematis BC: Significance of estrogen receptors and cathepsin D tissue detection in gastric adenocarcinoma. J Surg Oncol 1995, 58:176-183.
• [18]Karat D, Brotherick I, Shenton BK, Scott D, Raimes SA, Griffin SM: Expression of oestrogen and progesterone receptors in gastric cancer: a flow cytometric study. Br J Cancer 1999, 80:1271-1274.
• [19]Matsui M, Kojima O, Kawakami S, Uehara Y, Takahashi T: The prognosis of patients with gastric cancer possessing sex hormone receptors. Surg Today 1992, 22:421-425.
• [20]Machado JC, Carneiro F, Gärtner F, Ribeiro P, Sobrinho-Simões M: Female sex hormone receptors are not involved in gastric carcinogenesis. A biochemical and immunohistochemical study. Eur J Cancer Prev 1994, 3(Suppl 2):31-37.
• [21]Chaubert P, Bouzourene H, Saraga E: Estrogen and progesterone receptors and pS2 and ERD5 antigens in gastric carcinomas from the European population. Mod Pathol 1996, 9:189-193.
• [22]Matsuyama S, Ohkura Y, Eguchi H, Kobayashi Y, Akagi K, Uchida K, Nakachi K, Gustafsson JA, Hayashi S: Estrogen receptor beta is expressed in human stomach adenocarcinoma. J Cancer Res Clin Oncol 2002, 128:319-324.
• [23]Takano N, Iizuka N, Hazama S, Yoshino S, Tangoku A, Oka M: Expression of estrogen receptor-alpha and -beta mRNAs in human gastric cancer. Cancer Lett 2002, 176:129-135.
• [24]Wang M, Pan JY, Song GR, Chen HB, An LJ, Qu SX: Altered expression of estrogen receptor alpha and beta in advanced gastric adenocarcinoma: correlation with prothymosin alpha and clinicopathological parameters. Eur J Surg Oncol 2007, 33:195-201.
• [25]Guo JL, Xu CY, Jiang ZN, Dong MJ, Xie SD, Shen JG, Cao J, Wang LB: Estrogen receptor beta variants mRNA expressions in gastric cancer tissues and association with clinicopathologic parameters. Hepatogastroenterology 2010, 57:1584-1588.
• [26]Xu CY, Guo JL, Jiang ZN, Xie SD, Shen JG, Shen JY, Wang LB: Prognostic role of estrogen receptor alpha and estrogen receptor beta in gastric cancer. Ann Surg Oncol 2010, 17:2503-2509.
• [27]Ryu WS, Kim JH, Jang YJ, Park SS, Um JW, Park SH, Kim SJ, Mok YJ, Kim CS: Expression of estrogen receptors in gastric cancer and their clinical significance. J Surg Oncol 2012, 106:456-461.
• [28]Kominea A, Konstantinopoulos PA, Kapranos N, Vandoros G, Gkermpesi M, Andricopoulos P, Artelaris S, Savva S, Varakis I, Sotiropoulou-Bonikou G, Papavassiliou AG: Androgen receptor (AR) expression is an independent unfavorable prognostic factor in gastric cancer. J Cancer Res Clin Oncol 2004, 130:253-258.
• [29]Kononen J, Bubendorf L, Kallioniemi A, Bärlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 1998, 4:844-847.
• [30]Kallioniemi OP, Wagner U, Kononen J, Sauter G: Tissue microarray technology for high-throughput molecular profiling of cancer. Hum Mol Genet 2001, 10:657-662.
• [31]Allred DC, Clark GM, Elledge R, Fuqua SA, Brown RW, Chamness GC, Osborne CK, McGuire WL: Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 1993, 85:200-206.
• [32]Raso MG, Behrens C, Herynk MH, Liu S, Prudkin L, Ozburn NC, Woods DM, Tang X, Mehran RJ, Moran C, Lee JJ, Wistuba II: Immunohistochemical expression of estrogen and progesterone receptors identifies a subset of NSCLCs and correlates with EGFR mutation. Clin Cancer Res 2009, 15:5359-5368.
• [33]Verma MK, Miki Y, Abe K, Niikawa H, Sasano H: Cytoplasmic estrogen receptor β as a potential marker in human non-small cell lung carcinoma. Expert Opin Ther Targets 2012, 16(Suppl 1):S91-S102.
• [34]Chandanos E, Lagergren J: Oestrogen and the enigmatic male predominance of gastric cancer. Eur J Cancer 2008, 44:2397-2403.
• [35]Aranda A, Pascual A: Nuclear hormone receptors and gene expression. Physiol Rev 2001, 81:1269-1304.
• [36]Harrison JD, Morris DL, Ellis IO, Jones JA, Jackson I: The effect of tamoxifen and estrogen receptor status on survival in gastric carcinoma. Cancer 1989, 64:1007-1010.