Skip to main content

Advertisement

SpringerLink
Log in

Expression of CD44 variant 6 and its prognostic value in benign and malignant endometrial tissue

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

CD44 expression in both the early and metastatic phases of many epithelial and non-epithelial cancers is strongly prognostic. The objective of the study is to evaluate whether there is any relationship between the expression of CDD44v6 and endometrial cancer (EC) staging and prognosis.

Methods

This retrospective study included 60 EC patients for whom surgical staging was performed between 2000 and 2006. Twenty-eight randomly selected patients with normal endometria served as the control group. We immunohistochemically evaluated membranous and cytoplasmic CD44v6 staining in tissue paraffin blocks. The results were graded as positive or negative.

Results

Membranous staining in both advanced and early stage EC patients was significantly higher than that in the control group (p = 0.002). The extent of either membranous or cytoplasmic staining in both advanced- and early stage patients did not differ significantly by age, tumor grade, stage, extent of myometrial invasion, lymph node involvement, cytology, adnexal involvement, or omental spreading. In advanced-stage patients, neither papillary serous not clear cell cancers exhibited cytoplasmic staining.

Conclusions

CD44v6 membranous staining can be useful for differentiating malignant from benign endometrial tissue. However, staining is not associated with EC staging or prognosis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Behzad F, Seif MW, Campbell S et al (1994) Expression of two isoforms of CD44 in human endometrium. Biol Reprod 51:739–747

    Article  CAS  PubMed  Google Scholar 

  2. Afify AM, Craig S, Paulino AF (2006) Temporal variation in the distribution of hyaluronic acid, CD44 s, and CD44v6 in the human endometrium across the menstrual cycle. Appl Immunohistochem Mol Morphol 14:328–333

    Article  CAS  PubMed  Google Scholar 

  3. Afify AM, Craig S, Paulino AF et al (2005) Expression of hyaluronic acid and its receptors, CD44 s and CD44v6, in normal, hyperplastic, and neoplastic endometrium. Ann Diagn Pathol 9:312–318

    Article  PubMed  Google Scholar 

  4. Saegusa M, Hashimura M, Okayasu I (1998) CD44 expression in normal, hyperplastic, and malignant endometrium. J Pathol 184:297–306

    Article  CAS  PubMed  Google Scholar 

  5. Woodman AC, Sugiyama M, Yoshida K et al (1996) Analysis of anomalous CD44 gene expression in human breast, bladder, and colon cancer and correlation of observed mRNA and protein isoforms. Am J Pathol 149:1519–1530

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Koopman G, Heider KH, Horst E et al (1993) Activated human lymphocytes and aggressive non-Hodgkin’s lymphomas express a homologue of the rat metastasis-associated variant of CD44. J Exp Med 177:897–904

    Article  CAS  PubMed  Google Scholar 

  7. Rodriguez C, Monges G, Rouanet P et al (1995) CD44 expression patterns in breast and colon tumors: a PCR-based study of splice variants. Int J Cancer 64:347–354

    Article  CAS  PubMed  Google Scholar 

  8. Yamaguchi A, Saito M, Gio T et al (1995) Expression of CD44 variant exons 8–10 in gastric cancer. Jpn J Cancer Res 86:1166–1171

    Article  CAS  PubMed  Google Scholar 

  9. Kallakury BV, Yang F, Figge J et al (1996) Decreased levels of CD44 protein and mRNA in prostate carcinoma. Correlation with tumor grade and ploidy. Cancer 78:1461–1469

    Article  CAS  PubMed  Google Scholar 

  10. Assimakopoulos D, Kolettas E, Patrikakos G et al (2002) The role of CD44 in the development and prognosis of head and neck squamous cell carcinomas. Histol Histopathol 17:1269–1281

    CAS  PubMed  Google Scholar 

  11. Naor D, Sionov RV, Ish-Shalom D (1997) CD44: structure, function, and association with the malignant process. Adv Cancer Res 71:241–319

    Article  CAS  PubMed  Google Scholar 

  12. Faleiro-Rodrigues C, Lopes C (2004) E-cadherin, CD44 and CD44v6 in squamous intraepithelial lesions and invasive carcinomas of the uterine cervix: an immunohistochemical study. Pathobiology 71:329–336

    Article  CAS  PubMed  Google Scholar 

  13. Saegusa M, Hashimura M, Machida D et al (1999) Down-regulation of CD44 standard and variant isoforms during the development and progression of uterine cervical tumours. J Pathol 187:173–183

    Article  CAS  PubMed  Google Scholar 

  14. Hong SC, Song JY, Lee JK et al (2006) Significance of CD44v6 expression in gynecologic malignancies. J Obstet Gynaecol Re 32:379–386

    Article  CAS  Google Scholar 

  15. Elzarkaa AA, Sabaa BE, Abdelkhalik D et al (2016) Clinical relevance of CD44 surface expression in advanced stage serous epithelial ovarian cancer: a prospective study. J Cancer Res Clin Oncol 142:949–958

    Article  CAS  PubMed  Google Scholar 

  16. Zhao L, Gu C, Huang K, Zhang Z et al (2016) The prognostic value and clinicopathological significance of CD44 expression in ovarian cancer: a meta-analysis. Arch Gynecol Obstet 294:1019–1029

    Article  CAS  PubMed  Google Scholar 

  17. Wojciechowski M, Krawczyk T, Śmigielski J et al (2015) CD44 expression in curettage and postoperative specimens of endometrial cancer. Arch Gynecol Obstet 291:383–390

    Article  CAS  PubMed  Google Scholar 

  18. Fujita N, Yaegashi N, Ide Y et al (1994) Expression of CD44 in normal human versus tumor endometrial tissues: possible implication of reduced expression of CD44 in lymph-vascular space involvement of cancer cells. Cancer Res 54:3922–3928

    CAS  PubMed  Google Scholar 

  19. Kainz C, Kohlberger P, Sliutz G et al (1995) Splice variants of CD44 in human cervical cancer stage IB to IIB. Gynecol Oncol 57:383–387

    Article  CAS  PubMed  Google Scholar 

  20. Hoshimoto K, Yamauchi N, Takazawa Y et al (2003) CD44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker. Pathol Res Pract 199:71–77

    Article  PubMed  Google Scholar 

  21. Gun BD, Bahadir B, Bektas S et al (2012) Clinicopathological significance of fascin and CD44v6 expression in endometrioid carcinoma. Diagn Pathol 7:80

    Article  PubMed  PubMed Central  Google Scholar 

  22. Stokes GN, Shelton JB Jr, Zahn CM et al (2002) Association of CD44 isoform immunohistochemical expression with myometrial and vascular invasion in endometrioid endometrial carcinoma. Gynecol Oncol 84:58–61

    Article  PubMed  Google Scholar 

  23. Tokumo K, Kodama J, Seki N et al (1998) CD44 exon v6 correlates with cellular differentiation but not with progression and metastasis of cervical cancer. Eur J Cancer 34:2107–2111

    Article  CAS  PubMed  Google Scholar 

  24. Ayhan A, Tok EC, Bildirici I et al (2001) Overexpression of CD44 variant 6 in human endometrial cancer and its prognostic significance. Gynecol Oncol 80:355–358

    Article  CAS  PubMed  Google Scholar 

  25. Yorishima T, Nagai N, Ohama K (1997) Expression of CD44 alternative splicing variants in primary and lymph node metastatic lesions of gynecological cancer. Hiroshima J Med Sci 46:21–29

    CAS  PubMed  Google Scholar 

  26. Leblanc M, Poncelet C, Soriano D et al (2001) Alteration of CD44 and cadherins expression: possible association with augmented aggressiveness and invasiveness of endometrial carcinoma. Virchows Arch 438:78–85

    Article  CAS  PubMed  Google Scholar 

  27. Soslow RA, Shen PU, Isacson C et al (1998) The CD44v6-negative phenotype in high-grade uterine carcinomas correlates with serous histologic subtype. Mod Pathol 11:194–199

    CAS  PubMed  Google Scholar 

  28. Sugino T, Gorham H, Yoshida K (1996) Progressive loss of CD44 gene expression in invasive bladder cancer. Am J Pathol 149:873–882

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Albers A, Thie M, Hohn HP et al (1995) Differential expression and localization of integrins and CD44 in the membrane domains of human uterine epithelial cells during the menstrual cycle. Acta Anat 153:12–19

    Article  CAS  PubMed  Google Scholar 

  30. Poncelet C, Leblanc M, Walker-Combrouze F, Soriano D, Feldmann G, Madelenat P et al (2002) Expression of cadherins and CD44 isoforms in human endometrium and peritoneal endometriosis. Acta Obstet Gynecol Scand 81:195–203

    Article  PubMed  Google Scholar 

Download references

Author contributions

HKC: protocol and project development, data collection, data analysis, and manuscript writing. MG: project development, data management, data analysis, manuscript writing, and editing. FO: project development and manuscript editing. DK: protocol development, data management, and data analysis. AE: data management and data analysis.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Ankara University School of Medicine, Ankara, Turkey

    Hatice Kansu-Celik, Mete Gungor & Firat Ortac

  2. Department of Pathology, Ankara University School of Medicine, Ankara, Turkey

    Duygu Kankaya & Arzu Ensari

Authors
  1. Hatice Kansu-Celik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mete Gungor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Firat Ortac
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Duygu Kankaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arzu Ensari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hatice Kansu-Celik.

Ethics declarations

Conflict of interest

We declare that we have no conflict of interest.

Funding

None.

Ethical approval

All procedures performed in 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. The project was approved by the Ethical Committee of the Ankara University (Verdict No. 21/2006, June 2006).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kansu-Celik, H., Gungor, M., Ortac, F. et al. Expression of CD44 variant 6 and its prognostic value in benign and malignant endometrial tissue. Arch Gynecol Obstet 296, 313–318 (2017). https://doi.org/10.1007/s00404-017-4430-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-017-4430-9

Keywords

Search

Navigation