Skip to main content
Log in

Stanniocalcin-2 May Be a Potentially Valuable Prognostic Marker in Endometrial Cancer: a Preliminary Study

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

In the current study, we primarily aimed to investigate stanniocalcin-2 (STC2) protein expression pattern in hysterectomy specimens from patients with endometrioid type endometrial cancer (EC) using immunohistochemistry. Secondly, in order to clarify its prognostic impact, we examined relationships of the expression levels of STC2 with clinicopathologic features and outcome of patients. Histopathology slides of 49 patients were stained with the monoclonal mouse antibody targeting STC2 protein. The expression levels of STC2 were classified based on three-tiered semiquantitative scheme: negative expression, expression level of 0; low-expression, expression level of 1+; and high-expression, expression levels of 2+ and 3+. Recurrence-free survival (RFS) was used as the primary prognostic outcome. Immunohistochemical analysis revealed that 73.5% of tissue samples exhibited positive staining with STC2. The intensity of staining with STC2 was weak in 40.8%, moderate in 22.4%, and strong in 10.2%. Thirty-eight percent of samples showed negative expression; 18.4%, low-expression (1+); and 42.8%, high-expression (2 to 3+). High-expression of STC2 was significantly associated with grade 2–3 tumors (p = 0.026) and disease recurrence (p = 0.013). Multivariate analysis revealed that both the tumor grade and STC2 were independent predictors of disease recurrence. Kaplan-Meier analyses confirmed that patients with high-expression of STC2 had a significantly poorer RFS than those with negative or low STC2 expression (p = 0.037); although overall survival did not differ with respect to expression levels of STC2 (p = 0.148). In conclusion, high-expression of STC2 is a negative prognostic factor, associated with increased risk of recurrence in endometrioid EC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386. https://doi.org/10.1002/ijc.29210

    Article  CAS  Google Scholar 

  2. Ueda SM, Kapp DS, Cheung MK, Shin JY, Osann K, Husain A, Teng NN, Berek JS, Chan JK (2008) Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths. Am J Obstet Gynecol 198:218.e1–218.e6. https://doi.org/10.1016/j.ajog.2007.08.075

    Article  Google Scholar 

  3. Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, Heintz AP, Ngan HY, Pecorelli S (2006) Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological Cancer. Int J Gynaecol Obstet 95(Suppl 1):S105–S143

    Article  PubMed  Google Scholar 

  4. Banno K, Kisu I, Yanokura M, Masuda K, Ueki A, Kobayashi Y, Susumu N, Aoki D (2012) Epigenetics and genetics in endometrial cancer: new carcinogenic mechanisms and relationship with clinical practice. Epigenomics 4:147–162. https://doi.org/10.2217/epi.12.13

    Article  CAS  PubMed  Google Scholar 

  5. Chu SJ, Zhang J, Zhang R, Lu WW, Zhu JS (2015) Evolution and functions of stanniocalcins in cancer. Int J Immunopathol Pharmacol 28:14–20. https://doi.org/10.1177/0394632015572745

    Article  CAS  PubMed  Google Scholar 

  6. Takei Y, Yamamoto H, Sato T, Otani A, Kozai M, Masuda M, Taketani Y, Muto-Sato K, Lanske B, Takeda E (2012) Stanniocalcin 2 is associated with ectopic calcification in α-klotho mutant mice and inhibits hyperphosphatemia-induced calcification in aortic vascular smooth muscle cells. Bone 50:998–1005. https://doi.org/10.1016/j.bone.2012.01.006

    Article  CAS  PubMed  Google Scholar 

  7. Ziello JE, Jovin IS, Huang Y (2007) Hypoxia-inducible factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J Biol Med 80:51–60

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Kim PH, Na SS, Lee B, Kim JH, Cho JY (2015) Stanniocalcin 2 enhances mesenchymal stem cell survival by suppressing oxidative stress. BMB Rep 48:702–707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhong H, Hanrahan C, van der Poel H, Simons JW (2001) Hypoxia-inducible factor 1alpha and 1beta proteins share common signaling pathways in human prostate cancer cells. Biochem Biophys Res Commun 284:352–356

    Article  CAS  PubMed  Google Scholar 

  10. Zagzag D, Zhong H, Scalzitti JM, Laughner E, Simons JW, Semenza GL (2000) Expression of hypoxia-inducible factor 1alpha in brain tumors: association with angiogenesis, invasion, and progression. Cancer 88:2606–2618

    Article  CAS  PubMed  Google Scholar 

  11. Arigami T, Uenosono Y, Ishigami S, Yanagita S, Hagihara T, Haraguchi N, Matsushita D, Hirahara T, Okumura H, Uchikado Y, Nakajo A, Hokita S, Natsugoe S (2013) Clinical significance of stanniocalcin 2 expression as a predictor of tumor progression in gastric cancer. Oncol Rep 30:2838–2844. https://doi.org/10.3892/or.2013.2775

    Article  CAS  PubMed  Google Scholar 

  12. Zhang ZH, Wu YG, Qin CK, Rong ZH, Su ZX, Xian GZ (2014) Stanniocalcin 2 expression predicts poor prognosis of hepatocellular carcinoma. Oncol Lett 8:2160–2164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Shen XJ, Gu K, Shi JP, Yao JQ, Wu JC (2014) Increased expression of stanniocalcin 2 is associated with tumor progression after radiotherapy in patients with cervical carcinoma. Int J Clin Exp Pathol 7:8770–8776

    PubMed  PubMed Central  Google Scholar 

  14. Zhou H, Li YY, Zhang WQ, Lin D, Zhang WM, Dong WD (2014) Expression of stanniocalcin-1 and stanniocalcin-2 in laryngeal squamous cell carcinoma and correlations with clinical and pathological parameters. PLoS One 9:e95466. https://doi.org/10.1371/journal.pone.0095466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen B, Zeng X, He Y, Wang X, Liang Z, Liu J, Zhang P, Zhu H, Xu N, Liang S (2016) STC2 promotes the epithelial-mesenchymal transition of colorectal cancer cells through AKT-ERK signaling pathways. Oncotarget 7:71400–71416. https://doi.org/10.18632/oncotarget.12147

    Article  PubMed  PubMed Central  Google Scholar 

  16. Dondeti VR, Wubbenhorst B, Lal P, Gordan JD, D'Andrea K, Attiyeh EF, Simon MC, Nathanson KL (2012) Integrative genomic analyses of sporadic clear cell renal cell carcinoma define disease subtypes and potential new therapeutic targets. Cancer Res 72:112–121. https://doi.org/10.1158/0008-5472.CAN-11-1698

    Article  CAS  PubMed  Google Scholar 

  17. Law AY, Wong CK (2010) Stanniocalcin-2 promotes epithelial-mesenchymal transition and invasiveness in hypoxic human ovarian cancer cells. Exp Cell Res 316:3425–3434. https://doi.org/10.1016/j.yexcr.2010.06.026

    Article  CAS  PubMed  Google Scholar 

  18. Yang S, Ji Q, Chang B, Wang Y, Zhu Y, Li D, Huang C, Wang Y, Sun G, Zhang L, Guan Q, Xiang J, Wei W, Lu Z, Liao T, Meng J, Wang Z, Ma B, Zhou L, Wang Y, Yang G (2017) STC2 promotes head and neck squamous cell carcinoma metastasis through modulating the PI3K/AKT/snail signaling. Oncotarget 8:5976–5991. https://doi.org/10.18632/oncotarget.13355

    Article  PubMed  Google Scholar 

  19. Terakawa N, Kanamori Y, Yoshida S (2003) Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer. Endocr Relat Cancer 10:203–208

    Article  CAS  PubMed  Google Scholar 

  20. Cully M, You H, Levine AJ, Mak TW (2006) Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 6:184–192

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors received no financial support for the research, authorship, and/or publication of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hulya Ayik Aydin.

Ethics declarations

Conflicts of Interest

The authors declare no conflicts of interest.

Ethical Approval

All procedures performed involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study has been approved by Ethics Committee of the Akdeniz University School of Medicine. A written informed consent is not required for this type of retrospective study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aydin, H.A., Toptas, T., Bozkurt, S. et al. Stanniocalcin-2 May Be a Potentially Valuable Prognostic Marker in Endometrial Cancer: a Preliminary Study. Pathol. Oncol. Res. 25, 751–757 (2019). https://doi.org/10.1007/s12253-018-00576-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-018-00576-y

Keywords

Navigation