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Tumor Biology

, Volume 33, Issue 6, pp 2227–2235 | Cite as

Different effects of ERβ and TROP2 expression in Chinese patients with early-stage colon cancer

  • Yu-Jing Fang
  • Guo-Qiang Wang
  • Zhen-Hai Lu
  • Lin Zhang
  • Ji-Bin Li
  • Xiao-Jun Wu
  • Pei-Rong Ding
  • Qing-Jian Ou
  • Mei-Fang Zhang
  • Wu Jiang
  • Zhi-Zhong Pan
  • De-Sen Wan
Research Article

Abstract

Estrogen receptor beta (ERβ) and TROP2 expressed in colon carcinoma and might play an important role there. We explored the relationship of ERβ and TROP2 expression with the prognosis of early-stage colon cancer. ERβ and TROP2 levels were assessed by immunohistochemistry in normal mucosa and tumoral tissues from 220 Chinese patients with T3N0M0 (stage IIa) and T4N0M0 (stage IIb) colon cancer in the Cancer Center, Sun Yat-sen University, who underwent curative surgical resection between 1995 and 2003. The Cox proportional hazards regression model was applied to analyze the overall survival (OS) data, and the ROC curve, Kaplan–Meier estimate, log rank test, and Jackknife method were used to show the effect of ERβ and TROP2 expression at different stages of cancer. The 5-year survival rates were not significantly different between the patients with stage IIa and stage IIb colon cancer (83 vs. 80 %, respectively). The high expression of ERβ was related to decreasing OS in stage IIa and stage IIb colon cancer, while the high expression of TROP2 was related to decreasing OS in stage IIb colon cancer. The expression of ERβ and TROP2 has tumor-suppressive and tumor-promoting effect in stage IIa and stage IIb colon cancer, respectively.

Keywords

TROP2 Estrogen receptor beta Colon cancer Prognosis 

Notes

Acknowledgment

This study was supported by a grant from the National Natural Science Foundation of the Republic of China (grant no. 81101861) to Dr. Yu-Jing Fang.

Conflicts of interest

None

References

  1. 1.
    Honma N, Saji S, Kurabayashi R, Aida J, Arai T, Horii R, et al. Oestrogen receptor-beta1 but not oestrogen receptor-betacx is of prognostic value in apocrine carcinoma of the breast. APMIS. 2008;116:923–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Batistatou A, Kyzas PA, Goussia A, Arkoumani E, Voulgaris S, Polyzoidis K, et al. Estrogen receptor beta (ERbeta) protein expression correlates with BAG-1 and prognosis in brain glial tumours. J Neurooncol. 2006;77:17–23.PubMedCrossRefGoogle Scholar
  3. 3.
    Nose N, Sugio K, Oyama T, Nozoe T, Uramoto H, Iwata T, et al. Association between estrogen receptor-beta expression and epidermal growth factor receptor mutation in the postoperative prognosis of adenocarcinoma of the lung. J Clin Oncol. 2009;27:411–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Witte D, Chirala M, Younes A, Li Y, Younes M. Estrogen receptor beta is expressed in human colorectal adenocarcinoma. Hum Pathol. 2001;32:940–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Fang YJ, Lu ZH, Wang F, Wu XJ, Li LR, Zhang LY, et al. Prognostic impact of ERbeta and MMP7 expression on overall survival in colon cancer. Tumor Biol. 2010;31:651–8.CrossRefGoogle Scholar
  6. 6.
    Liu L, Chirala M, Younes M. Expression of estrogen receptor-beta isoforms in Barrett's metaplasia, dysplasia and esophageal adenocarcinoma. Anticancer Res. 2004;24:2919–24.PubMedGoogle Scholar
  7. 7.
    Matsuyama S, Ohkura Y, Eguchi H, Kobayashi Y, Akagi K, Uchida K, et al. Estrogen receptor beta is expressed in human stomach adenocarcinoma. J Cancer Res Clin Oncol. 2002;128:319–24.PubMedCrossRefGoogle Scholar
  8. 8.
    Abe K, Miki Y, Ono K, Mori M, Kakinuma H, Kou Y, et al. Highly concordant coexpression of aromatase and estrogen receptor beta in non-small cell lung cancer. Hum Pathol. 2010;41:190–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Lai JS, Brown LG, True LD, Hawley SJ, Etzioni RB, Higano CS, et al. Metastases of prostate cancer express estrogen receptor-beta. Urology. 2004;64:814–20.PubMedCrossRefGoogle Scholar
  10. 10.
    Pais V, Leav I, Lau KM, Jiang Z, Ho SM. Estrogen receptor-beta expression in human testicular germ cell tumors. Clin Cancer Res. 2003;9:4475–82.PubMedGoogle Scholar
  11. 11.
    Iwao K, Miyoshi Y, Ooka M, Ishikawa O, Ohigashi H, Kasugai T, et al. Quantitative analysis of estrogen receptor-alpha and -beta messenger RNA expression in human pancreatic cancers by real-time polymerase chain reaction. Cancer Lett. 2001;170:91–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Deyrup AT, Tretiakova M, Khramtsov A, Montag AG. Estrogen receptor beta expression in vascular neoplasia: an analysis of 53 benign and malignant cases. Mod Pathol. 2004;17:1372–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Birkenkamp-Demtroder K, Olesen SH, Sørensen FB, Laurberg S, Laiho P, Aaltonen LA, et al. Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut. 2005;54:374–84.PubMedCrossRefGoogle Scholar
  14. 14.
    Nakashima K, Shimada H, Ochiai T, Kuboshima M, Kuroiwa N, Okazumi S, et al. Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinoma. Int J Cancer. 2004;112:1029–35.PubMedCrossRefGoogle Scholar
  15. 15.
    Santin AD, Zhan F, Bellone S, Palmieri M, Cane S, Bignotti E, et al. Gene expression profiles in primary ovarian serous papillary tumors and normal ovarian epithelium: identification of candidate molecular markers for ovarian cancer diagnosis and therapy. Int J Cancer. 2004;112:14–25.PubMedCrossRefGoogle Scholar
  16. 16.
    Wang J, Day R, Dong Y, Weintraub SJ, Michel L. Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancers. Mol Cancer Ther. 2008;7:280–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Cubas R, Li M, Chen C, Yao Q. Trop2: a possible therapeutic target for late stage epithelial carcinomas. Biochim Biophys Acta. 2009;1796:309–14.PubMedGoogle Scholar
  18. 18.
    Fong D, Spizzo G, Gostner JM, Gastl G, Moser P, Krammel C, et al. TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity. Mod Pathol. 2008;21:186–91.PubMedGoogle Scholar
  19. 19.
    Fong D, Moser P, Krammel C, Gostner JM, Margreiter R, Mitterer M, et al. High expression of TROP2 correlates with poor prognosis in pancreatic cancer. Br J Cancer. 2008;99:1290–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Mühlmann G, Spizzo G, Gostner J, Zitt M, Maier H, Moser P, et al. TROP2 expression as prognostic marker for gastric carcinoma. J Clin Pathol. 2009;62:152–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Fang YJ, Lu ZH, Wang GQ, Pan ZZ, Zhou ZW, Yun JP, et al. Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer. Int J Color Dis. 2009;24:875–84.CrossRefGoogle Scholar
  22. 22.
    Ohmachi T, Tanaka F, Mimori K, Inoue H, Yanaga K, Mori M. Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res. 2006;12:3057–63.PubMedCrossRefGoogle Scholar
  23. 23.
    Huang E, Cheng SH, Dressman H, Pittman J, Tsou MH, Horng CF, et al. Gene expression predictors of breast cancer outcomes. Lancet. 2003;361:1590–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Konstantinopoulos PA, Kominea A, Vandoros G, Sykiotis GP, Andricopoulos P, Varakis I, et al. Oestrogen receptor beta (ERβ) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour's dedifferentiation. Eur J Cancer. 2003;39:1251–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Jassam N, Bell SM, Speirs V, Quirke P. Loss of expression of oestrogen receptor beta in colon cancer and its association with Dukes' staging. Oncol Rep. 2005;14:17–21.PubMedGoogle Scholar
  26. 26.
    Wong NACS, Malcomson RDG, Jodrell DI, Groome NP, Harrison DJ, Saunders PTK. ER beta isoform expression in colorectal carcinoma: an in vivo and in vitro study of clinicopathological and molecular correlates. J Pathol. 2005;207:53–60.PubMedCrossRefGoogle Scholar
  27. 27.
    Sumi K, Matsuyama S, Kitajima Y, Miyazaki K. Loss of estrogen receptor B expression at cancer front correlates with tumor progression and poor prognosis of gallbladder cancer. Oncol Rep. 2004;12:979–84.PubMedGoogle Scholar
  28. 28.
    Wada-Hiraike O, Imamov O, Hiraike H, Hultenby K, Schwend T, Omoto Y, et al. Role of estrogen receptor beta in colonic epithelium. Proc Natl Acad Sci U S A. 2006;103:2959–64.PubMedCrossRefGoogle Scholar
  29. 29.
    Barone M, Scavo MP, Papagni S, Piscitelli D, Guido R, Di Lena M, et al. ER beta expression in normal, adenomatous and carcinomatous tissues of patients with familial adenomatous polyposis. Scand J Gastroenterol. 2010;45:1320–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Cho NL, Javid SH, Carothers AM, Redston M, Bertagnolli MM. Estrogen receptors alpha and beta are inhibitory modifiers of Apc-dependent tumorigenesis in the proximal colon of Min/+ mice. Cancer Res. 2007;67:2366–72.PubMedCrossRefGoogle Scholar
  31. 31.
    Martineti V, Picariello L, Tognarini I, Sala SC, Gozzini A, Azzari C, et al. ER beta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components. Endocr Relat Cancer. 2005;12:455–69.PubMedCrossRefGoogle Scholar
  32. 32.
    Cubas R, Zhang S, Li M, Chen C, Yao Q. Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Mol Cancer. 2010;9:253.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Yu-Jing Fang
    • 1
    • 2
    • 3
  • Guo-Qiang Wang
    • 4
  • Zhen-Hai Lu
    • 1
    • 3
  • Lin Zhang
    • 3
    • 5
  • Ji-Bin Li
    • 6
  • Xiao-Jun Wu
    • 1
    • 3
  • Pei-Rong Ding
    • 1
    • 3
  • Qing-Jian Ou
    • 2
    • 3
  • Mei-Fang Zhang
    • 3
    • 7
  • Wu Jiang
    • 1
    • 3
  • Zhi-Zhong Pan
    • 1
    • 3
    • 8
  • De-Sen Wan
    • 1
    • 3
    • 8
  1. 1.Department of Colorectal Surgery, State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhouChina
  2. 2.Department of Experimental Research, State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhouChina
  3. 3.State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhouChina
  4. 4.Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
  5. 5.Department of Clinical Laboratory, State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhouChina
  6. 6.Department of Medical Statistics and Epidemiology, School of Public HealthSun Yat-sen UniversityGuangzhouChina
  7. 7.Department of Pathology, State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhouChina
  8. 8.Department of Colorectal Surgery, State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhouPeople’s Republic of China

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