The Chinese-German Journal of Clinical Oncology

, Volume 12, Issue 12, pp 586–591 | Cite as

Clinical implications and prognostic value of five biomarkers in endometrial carcinoma

  • Mingzhu Li
  • Lijun Zhao
  • Wenjuan Qi
  • Danhua Shen
  • Xiaoping Li
  • Jianliu Wang
  • Lihui WeiEmail author



The aim was to identify the relationship between ER, PR, P53, Ki-67, PTEN, the association with clinicopathological parameters and the correlation with survival.


We studied 190 cases of primary endometrial carcinoma in which ER, PR, Ki-67, P53, PTEN antigens were investigated with the use of immunohistochemical methods. To evaluate the correlations among immunohistochemical staining and the age, menopause status, histological type, FIGO stage, grading, depth of invasion, lymph nodes involvement and serum tumor marker. Survival analysis was assessed within single and combined biomarkers types.


The percentage of Ki-67 and P53 positive endometrial tumors was significantly higher in ER negative vs ER positive tumors (both P = 0.000). The same trend was evident in PR positive and negative group. The percentage of PTEN positive tumors was significantly higher in PR positive versus PR negative tumors (P = 0.021) but was no difference in different ER status. ER and PR status were significant predictors with FIGO staging, grading and recurrence. There was no clear association between PTEN positivity and clinicopathological parameters except more relevance with endometrioid histotype (P = 0.013). Positive Ki-67 or P53 was found to be strictly related to more aggressive features. There was statistically significant difference in different status of P53 and Ki-67 in survival time.


ER and PR positive tumors showed a statistically significant association with better clinical outcome, PR has more significant influence on prognosis. The percentage of positive Ki-67 or P53 was significantly higher in hormone-independent group versus in hormone-dependent group and combined Ki-67 and P53 may have more effect on prognosis in former group.

Key word

endometrial carcinoma immunohistochemistry clinical factors biomarkers 


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  1. 1.
    Morrison DH, Rahardja D, King E, et al. Tumour biomarker expression relative to age and molecular subtypes of invasive breast cancer. Br J Cancer, 2012,107: 382–387.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Miller DS, King LP. Gynecologic oncology group trials in uterine corpus malignancies: recent progress. J Gynecol Oncol, 2008, 19: 218–222.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Baak JP, Snijders W, van Diermen B, et al. Prospective multicenter validation confirms the prognostic superiority of the endometrial carcinoma prognostic index in international Federation of gynecology and obstetrics stage 1 and 2 endometrial carcinoma. J Clin Oncol, 2003, 21: 4214–4221.PubMedCrossRefGoogle Scholar
  4. 4.
    Mariani A, Webb MJ, Keeney GL, et al. Surgical stage I endometrial cancer: predictors of distant failure and death. Gynecol Oncol, 2002, 87: 274–280.PubMedCrossRefGoogle Scholar
  5. 5.
    Creasman WT, Soper JT, Mccarty KJ, et al. Influence of cytoplasmic steroid receptor content on prognosis of early stage endometrial carcinoma. Am J Obstet Gynecol, 1985, 151: 922–932.PubMedCrossRefGoogle Scholar
  6. 6.
    Suthipintawong C, Wejaranayang C, Vipupinyo C. Prognostic significance of ER, PR, Ki67, c-erbB-2, and p53 in endometrial carcinoma. J Med Assoc Thai, 2008, 91: 1779–1784.PubMedGoogle Scholar
  7. 7.
    Markova I, Duskova M, Lubusky M, et al. Selected immunohistochemical prognostic factors in endometrial cancer. Int J Gynecol Cancer, 2010, 20: 576–582.PubMedCrossRefGoogle Scholar
  8. 8.
    Ferrandina G, Ranelletti FO, Gallotta V, et al. Expression of cyclooxygenase-2 (COX-2), receptors for estrogen (ER), and progesterone (PR), p53, ki67, and neu protein in endometrial cancer. Gynecol Oncol, 2005, 98: 383–389.PubMedCrossRefGoogle Scholar
  9. 9.
    Lee EJ, Kim TJ, Kim DS, et al. p53 alteration independently predicts poor outcomes in patients with endometrial cancer: a clinicopathologic study of 131 cases and literature review. Gynecol Oncol, 2010, 116: 533–538.PubMedCrossRefGoogle Scholar
  10. 10.
    Lee YK, Park NH. Prognostic value and clinicopathological significance of p53 and PTEN in epithelial ovarian cancers. Gynecol Oncol, 2009, 112: 475–480.PubMedCrossRefGoogle Scholar
  11. 11.
    Yao YY, Xu WZ, Wang Y, et al. Relationships between the molecular biomarkers and the clinicopathologic features and prognosis in endometrial carcinoma. J Peking Univ (Chinese), 2011, 43: 743–748.Google Scholar
  12. 12.
    Ohkouchi T, Sakuragi N, Watari H, et al. Prognostic significance of Bcl-2, p53 overexpression, and lymph node metastasis in surgically staged endometrial carcinoma. Am J Obstet Gynecol, 2002, 187: 353–359.PubMedCrossRefGoogle Scholar
  13. 13.
    Skirnisdottir I, Seidal T. Prognostic impact of concomitant p53 and PTEN on outcome in early stage (FIGO I–II) epithelial ovarian cancer. Int J Gynecol Cancer, 2011, 21: 1024–1031.PubMedCrossRefGoogle Scholar
  14. 14.
    Sivridis E, Giatromanolaki A, Koukourakis M, et al. Endometrial carcinoma: association of steroid hormone receptor expression with low angiogenesis and bcl-2 expression. Virchows Arch, 2001, 438: 470–477.PubMedCrossRefGoogle Scholar
  15. 15.
    Bedolla R, Prihoda TJ, Kreisberg JI, et al. Determining risk of biochemical recurrence in prostate cancer by immunohistochemical detection of PTEN expression and Akt activation. Clin Cancer Res, 2007, 13: 3860–3867.PubMedCrossRefGoogle Scholar
  16. 16.
    Pourzand A, Fakhree MB, Hashemzadeh S, et al. Hormone receptor status in breast cancer and its relation to age and other prognostic factors. Breast Cancer (Auckl), 2011, 5: 87–92.Google Scholar
  17. 17.
    Zergeroglu S, Ozdemir HB, Ozel M, et al. The prognostic importance of proliferative activity and oestrogen receptor expression in stage I endometrial carcinomas. J Obstet Gynaecol, 2006, 26: 798–801.PubMedCrossRefGoogle Scholar
  18. 18.
    Fukuda K, Mori M, Uchiyama M, et al. Prognostic significance of progesterone receptor immunohistochemistry in endometrial carcinoma. Gynecol Oncol, 1998, 69: 220–225.PubMedCrossRefGoogle Scholar
  19. 19.
    Pansare V, Munkarah AR, Schimp V, et al. Increased expression of hypoxia-inducible factor 1alpha in type I and type II endometrial carcinomas. Mod Pathol, 2007, 20: 35–43.PubMedCrossRefGoogle Scholar
  20. 20.
    Fanning J, Brown S, Phibbs G, et al. Immunohistochemical evaluation is not prognostic for recurrence in fully staged high-risk endometrial cancer. Int J Gynecol Cancer, 2002, 12: 286–289.PubMedCrossRefGoogle Scholar
  21. 21.
    Sylvia M T, Kumar S, Dasari P. The expression of immunohistochemical markers estrogen receptor, progesterone receptor, Her-2-neu, p53 and Ki-67 in epithelial ovarian tumors and its correlation with clinicopathologic variables. Indian J Pathol Microbiol, 2012, 55: 33–37.PubMedCrossRefGoogle Scholar
  22. 22.
    Salvesen HB, Iversen OE, Akslen LA. Prognostic significance of angiogenesis and Ki-67, p53, and p21 expression: a population-based endometrial carcinoma study. J Clin Oncol, 1999, 17: 1382–1390.PubMedGoogle Scholar
  23. 23.
    Halperin R, Zehavi S, Habler L, et al. Comparative immunohistochemical study of endometrioid and serous papillary carcinoma of endometrium. Eur J Gynaecol Oncol, 2001, 22: 122–126.PubMedGoogle Scholar
  24. 24.
    Voss MA, Ganesan R, Ludeman L, et al. Should grade 3 endometrioid endometrial carcinoma be considered a type 2 cancer-a clinical and pathological evaluation. Gynecol Oncol, 2012, 124: 15–20.PubMedCrossRefGoogle Scholar
  25. 25.
    Alkushi A, Lim P, Coldman A, et al. Interpretation of p53 immunoreactivity in endometrial carcinoma: establishing a clinically relevant cut-off level. Int J Gynecol Pathol, 2004, 23: 129–137.PubMedCrossRefGoogle Scholar
  26. 26.
    Yamada KM, Araki M. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci, 2001, 114: 2375–2382.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Mingzhu Li
    • 1
  • Lijun Zhao
    • 1
  • Wenjuan Qi
    • 1
  • Danhua Shen
    • 1
  • Xiaoping Li
    • 1
  • Jianliu Wang
    • 1
  • Lihui Wei
    • 1
    Email author
  1. 1.Center of Gynecologic OncologyPeking University People’s HospitalBeijingChina

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