Skip to main content
Log in

MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138.

Methods

This is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC.

Results

Sensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761–0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138.

Conclusion

IHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE.

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

Availability of data and material

All data are available upon request.

References

  1. Kitaya K, Takeuchi T, Mizuta S, Matsubayashi H, Ishikawa T. Endometritis: new time, new concepts. Fertil Steril. 2018;110:344–50.

    Article  Google Scholar 

  2. Park HJ, Kim YS, Yoon TK, Lee WS. Chronic endometritis and infertility. Clin Exp Reprod Med. 2016;43:185–92.

    Article  Google Scholar 

  3. Moreno I, Cicinelli E, Garcia-Grau I, Gonzalez-Monfort M, Bau D, Vilella F, et al. The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology. Am J Obstet Gynecol. 2018;218(6):602.e1-602.e16.

    Article  Google Scholar 

  4. Drizi A, Djokovic D, Laganà AS, van Herendael B. Impaired inflammatory state of the endometrium: a multifaceted approach to endometrial inflammation. Current insights and future directions. Prz Menopauzalny. 2020;19(2):90–100. https://doi.org/10.5114/pm.2020.97863.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kimura F, Takebayashi A, Ishida M, Nakamura A, Kitazawa J, Morimune A, Hirata K, Takahashi A, Tsuji S, Takashima A, Amano T, Tsuji S, Ono T, Kaku S, Kasahara K, Moritani S, Kushima R, Murakami T. Review: Chronic endometritis and its effect on reproduction. J Obstet Gynaecol Res. 2019;45(5):951–60.

    Article  Google Scholar 

  6. Cicinelli E, Bettocchi S, de Ziegler D, Loizzi V, Cormio G, Marinaccio M, Trojano G, Crupano FM, Francescato R, Vitagliano A, Resta L. Chronic endometritis, a common disease hidden behind endometrial polyps in premenopausal women: first evidence from a case-control study. J Minim Invasive Gynecol. 2019;26(7):1346–50.

    Article  Google Scholar 

  7. Buzzaccarini G, Vitagliano A, Andrisani A, Santarsiero CM, Cicinelli R, Nardelli C, Ambrosini G, Cicinelli E. Chronic endometritis and altered embryo implantation: a unified pathophysiological theory from a literature systematic review. J Assist Reprod Genet. 2020;37(12):2897–911.

    Article  Google Scholar 

  8. Kitaya K. Prevalence of chronic endometritis in recurrent miscarriages. Fertil Steril. 2011;95:1156–8.

    Article  Google Scholar 

  9. Cicinelli E, Matteo M, Trojano G, Mitola PC, Tinelli R, Vitagliano A, et al. Chronic endometritis in patients with unexplained infertility: prevalence and effects of antibiotic treatment on spontaneous conception. Am J Reprod Immunol 2017. https://doi.org/10.1111/aji.12782.

  10. Vitagliano A, Saccardi C, Noventa M, Di Spiezio Sardo A, Saccone G, Cicinelli E, Pizzi S, Andrisani A, Litta PS. Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: a systematic review and meta-analysis. Fertil Steril. 2018;110(1):103-112.e1. https://doi.org/10.1016/j.fertnstert.2018.03.017.

    Article  PubMed  Google Scholar 

  11. McQueen DB, Bernardi LA, Stephenson MD. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertil Steril. 2014;101:1026–30.

    Article  Google Scholar 

  12. Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015;30:323–30.

    Article  Google Scholar 

  13. Johnston-MacAnanny EB, Hartnett J, Engmann LL, Nulsen JC, Sanders MM, Benadiva CA. Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril. 2010;93:437–41.

    Article  Google Scholar 

  14. Puente E, Alonso L, Laganà AS, Ghezzi F, Casarin J, Carugno J. Chronic endometritis: old problem, novel insights and future challenges. Int J Fertil Steril. 2020;13(4):250–6. https://doi.org/10.22074/ijfs.2020.5779.

    Article  CAS  PubMed  Google Scholar 

  15. Cicinelli E, Vitagliano A, Kumar A, Lasmar RB, Bettocchi S, Haimovich S, International Working Group for Standardization of Chronic Endometritis Diagnosis. Unified diagnostic criteria for chronic endometritis at fluid hysteroscopy: proposal and reliability evaluation through an international randomized-controlled observer study. Fertil Steril. 2019;112(1):162-173.e2. https://doi.org/10.1016/j.fertnstert.2019.03.004.

    Article  PubMed  Google Scholar 

  16. Li Y, Xu S, Yu S, Huang C, Lin S, Chen W, Mo M, Lian R, Diao L, Ding L, Zeng Y. Diagnosis of chronic endometritis: How many CD138+ cells/HPF in endometrial stroma affect pregnancy outcome of infertile women? Am J Reprod Immunol. 2020;85(5):e13369. https://doi.org/10.1111/aji.13369.

  17. Chen YQ, Fang RL, Luo YN, Luo CQ. Analysis of the diagnostic value of CD138 for chronic endometritis, the risk factors for the pathogenesis of chronic endometritis and the effect of chronic endometritis on pregnancy: a cohort study. BMC Womens Health. 2016;16(1):60.

    Article  Google Scholar 

  18. Parks RN, Kim CJ, Al-Safi ZA, Armstrong AA, Zore T, Moatamed NA. Multiple myeloma 1 transcription factor is superior to CD138 as a marker of plasma cells in endometrium. Int J Surg Pathol. 2019;27(4):372–9.

    Article  CAS  Google Scholar 

  19. Kannar V, Lingaiah HK, Sunita V. Evaluation of endometrium for chronic endometritis by using syndecan-1 in abnormal uterine bleeding. J Lab Physicians. 2012;15(4):69–73.

    Google Scholar 

  20. Kitaya K, Yasuo T. Immunohistochemistrical and clinicopathological characterization of chronic endometritis. Am J Reprod Immunol. 2011;66:410–5.

    Article  CAS  Google Scholar 

  21. Kitaya K, Tada Y, Taguchi S, Funabiki M, Hayashi T, Nakamura Y. Local mononuclear cell infiltrates in infertile patients with endometrial macropolyps versus micropolyps. Hum Reprod. 2012;27:3474–80.

    Article  CAS  Google Scholar 

  22. Kitaya K, Yasuo T. Inter-observer and intra-observer variability in immunohistochemical detection of endometrial stromal plasmacytes in chronic endometritis. Exp Ther Med. 2013;5(2):485–8.

    Article  Google Scholar 

  23. Falini B, Fizzotti M, Pucciarini A, Bigerna B, Marafioti T, Gambacorta M, Pacini R, Alunni C, Natali-Tanci L, Ugolini B, Sebastiani C, Cattoretti G, Pileri S, Dalla-Favera R, Stein H. A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. Blood. 2000;95(6):2084–92 (Erratum in: Blood. 2013 Oct 3;122(14):2523.).

    Article  CAS  Google Scholar 

  24. Wasco MJ, Fullen D, Su L, Ma L. The expression of MUM1 in cutaneous T-cell lymphoproliferative disorders. Hum Pathol. 2008;39(4):557–63.

    Article  CAS  Google Scholar 

  25. Gaidano G, Carbone A. MUM1: a step ahead toward the understanding of lymphoma histogenesis. Leukemia. 2000;14(4):563–6.

    Article  CAS  Google Scholar 

  26. Valsami S, Pappa V, Rontogianni D, Kontsioti F, Papageorgiou E, Dervenoulas J, Karmiris T, Papageorgiou S, Harhalakis N, Xiros N, Nikiforakis E, Economopoulos T. A clinicopathological study of B-cell differentiation markers and transcription factors in classical Hodgkin’s lymphoma: a potential prognostic role of MUM1/IRF4. Haematologica. 2007;92(10):1343–50.

    Article  CAS  Google Scholar 

  27. Tsuboi K, Iida S, Inagaki H, Kato M, Hayami Y, Hanamura I, Miura K, Harada S, Kikuchi M, Komatsu H, Banno S, Wakita A, Nakamura S, Eimoto T, Ueda R. MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies. Leukemia. 2000;14(3):449–56.

    Article  CAS  Google Scholar 

  28. Naresh KN. MUM1 expression dichotomises follicular lymphoma into predominantly, MUM1-negative low-grade and MUM1-positive high-grade subtypes. Haematologica. 2007;92(2):267–8.

    Article  Google Scholar 

  29. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, STROBE Initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 2007;335(7624):806–8. https://doi.org/10.1136/bmj.39335.541782.AD.

    Article  Google Scholar 

  30. Bayer-Garner IB, Korourian S. Plasma cells in chronic endometritis are easily identified when stained with syndecan-1. Mod Pathol. 2001;14:877–9.

    Article  CAS  Google Scholar 

  31. Cicinelli E, Matteo M, Tinelli R, Pinto V, Marinaccio M, Indraccolo U, De Ziegler D, Resta L. Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. Reprod Sci. 2014;21(5):640–7.

    Article  Google Scholar 

  32. Cicinelli E, Cicinelli R, Vitagliano A. Consistent evidence on the detrimental role of severe chronic endometritis on in vitro fertilization outcome and the reproductive improvement after antibiotic therapy: on the other hand, mild chronic endometritis appears a more intricate matter. Fertil Steril. 2021;116(2):345–6.

    Article  Google Scholar 

  33. Song D, He Y, Wang Y, Liu Z, Xia E, Huang X, Xiao Y, Li TC. Impact of antibiotic therapy on the rate of negative test results for chronic endometritis: a prospective randomized control trial. Fertil Steril. 2021;115(6):1549–56.

    Article  CAS  Google Scholar 

  34. Cicinelli E, Resta L, Loizzi V, Pinto V, Santarsiero C, Cicinelli R, Greco P, Vitagliano A. Antibiotic therapy versus no treatment for chronic endometritis: a case-control study. Fertil Steril. 2021;115(6):1541–8.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

University of Bari, University of Padua, University of Barcelona.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Giovanni Buzzaccarini.

Ethics declarations

Ethics approval

The study received local ethical approval.

Consent to participate

All patients gave their written consent for the procedure.

Consent for publication

All patients gave their written consent for the anonymous use of their clinical data for research purposes.

Conflict of interest

The authors declare no competing interests.

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

Cicinelli, E., Haimovich, S., De Ziegler, D. et al. MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining. J Assist Reprod Genet 39, 219–226 (2022). https://doi.org/10.1007/s10815-021-02356-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-021-02356-1

Keywords

Navigation