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Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expressions in type 2 endometrial cancer

Archives of Gynecology and Obstetrics volume 300, pages 377–382 (2019)Cite this article

Abstract

Purpose

The aim of this study was to evaluate prognostic importance of programmed death-1 (PD-1) and/ or programmed death-ligand 1 (PD-L1) expressions in type 2 endometrial cancer.

Study design

Formalin-fixed, paraffin-embedded tissue samples from 53 cases with type 2 endometrial cancer were analyzed. One-third of our cases had serous adenocarcinoma (32%), 11 had clear cell (21%) and 25 had mixed-type adenocarcinoma (47%). PD-1 and PD-L1 expressions in tumor tissue and microenvironment were detected by immunohistochemistry. Clinical and pathological characteristics including age, stage, initial symptom, surgical procedure, myometrial invasion, lymphovascular space invasion (LVSI), lymph node invasion, adjuvant therapy, and survival were reviewed. The Kaplan–Meier and Cox proportional hazards models were used to evaluate the prognostic factors.

Results

PD-1 expression in tumor tissue and microenvironment was detected in 22 (42%) and 28 (53%) cases, respectively. PD-L1 expression was detected in tumor and microenvironment in 8 (15%) and in 15 cases (28%), respectively. Expression of PD-1 and PD-L1 expressions in tumor area was associated with shorter survival (p = 0.006 and 0.001, respectively) but PD-1 and PD-L1 expressions in microenvironment were not found to be related with survival. PD-1 (p = 0.006) and PD-L1 expressions (p = 0.001) in addition to LVSI (p = 0.005), myometrial invasion (p = 0.015), lymph node involvement (p = 0.019), and suboptimal cytoreduction (p = 0.042), were found to be associated with poor prognostic indicators. PD-1 and PD-L1 expressions in tumor and lymph node involvement were determined as independent prognostic factors.

Conclusion

PD-1 and PD-L1 expressions in type 2 endometrial cancers were found to be poor prognostic indicators.

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References

  1. Suarez AA, Felix AS, Cohn DE (2017) Bokhman Redux: Endometrial cancer "types" in the 21st century. Gynecol Oncol 144(2):243–249

    Article  Google Scholar 

  2. Ueda SM, Kapp DS, Cheung MK, Shin JY, Osann K, Husain A et al (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(2):218.e1–6

    Article  Google Scholar 

  3. Murali R, Soslow RA, Weigelt B (2014) Classification of endometrial carcinoma: more than two types. Lancet Oncol 15(7):e268–e278

    Article  PubMed  PubMed Central  Google Scholar 

  4. Piulats JM, Guerra E, Gil-Martín M, Roman-Canal B, Gatius S, Sanz-Pamplona R et al (2017) Molecular approaches for classifying endometrial carcinoma. Gynecol Oncol 145(1):200–207

    Article  CAS  PubMed  Google Scholar 

  5. Hamanishi J, Mandai M, Matsumura N, Abiko K, Baba T, Konishi I (2016) PD-1/PD-L1 blockade in cancer treatment: perspectives and issues. Int J Clin Oncol 21(3):462–473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gargiulo P, Della Pepa C, Berardi S, Califano D, Scala S, Buonaguro L et al (2016) Tumor genotype and immune microenvironment in POLE-ultramutated and MSI-hypermutated endometrial cancers: New candidates for checkpoint blockade immunotherapy? Cancer Treat Rev 48:61–68

    Article  CAS  PubMed  Google Scholar 

  7. Chen K, Cheng G, Zhang F, Zhang N, Li D, Jin J et al (2016) Prognostic significance of programmed death-1 and programmed death-ligand 1 expression in patients with esophageal squamous cell carcinoma. Oncotarget 7(21):30772–30780

    PubMed  PubMed Central  Google Scholar 

  8. Balkwill FR, Capasso M, Hagemann T (2012) The tumor microenvironment at a glance. J Cell Sci 125(Pt 23):5591–5596

    Article  CAS  Google Scholar 

  9. Xiao X, Dong D, He W, Song L, Wang Q, Yue J et al (2018) Mismatch repair deficiency is associated with MSI phenotype, increased tumor-infiltrating lymphocytes and PD-L1 expression in immune cells in ovarian cancer. Gynecol Oncol 149(1):146–154

    Article  CAS  PubMed  Google Scholar 

  10. Vanderstraeten A, Luyten C, Verbist G, Tuyaerts S, Amant F (2014) Mapping the immunosuppressive environment in uterine tumors: implications for immunotherapy. Cancer Immunol Immunother 63(6):545–557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yamashita H, Nakayama K, Ishikawa M, Nakamura K, Ishibashi T, Sanuki K, et al. (2017) Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer. Oncotarget 31;9(5):5652–5664.

  12. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD et al (2015) PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 372(26):2509–2520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK et al (2017) Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357(6349):409–413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sloan EA, Ring KL, Willis BC, Modesitt SC, Mills AM (2017) PD-L1 Expression in Mismatch Repair-deficient Endometrial Carcinomas, Including Lynch Syndrome-associated and MLH1 Promoter Hypermethylated Tumors. Am J Surg Pathol 41(3):326–333

    Article  PubMed  Google Scholar 

  15. Bregar A, Deshpande A, Grange C, Zi T, Stall J, Hirsch H et al (2017) Characterization of immune regulatory molecules B7–H4 and PD-L1 in low and high grade endometrial tumors. Gynecol Oncol 145(3):446–452

    Article  CAS  PubMed  Google Scholar 

  16. Eggink FA, Van Gool IC, Leary A, Pollock PM, Crosbie EJ, Mileshkin L et al (2016) Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE-mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition. Oncoimmunology 6(2):e1264565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Howitt BE, Shukla SA, Sholl LM, Ritterhouse LL, Watkins JC, Rodig S et al (2015) Association of Polymerase e-Mutated and Microsatellite-Instable Endometrial Cancers with Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1. JAMA Oncol 1(9):1319–1323

    Article  PubMed  PubMed Central  Google Scholar 

  18. Paydas S, Bagir EK, Deveci MA, Gonlusen G (2016) Clinical and prognostic significance of PD-1 and PD-L1 expression in sarcomas. Med Oncol 33(8):93

    Article  CAS  PubMed  Google Scholar 

  19. D’Incecco A, Andreozzi M, Ludovini V, Rossi E, Capodanno A, Landi L et al (2015) PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer 112(1):95–102

    Article  CAS  PubMed  Google Scholar 

  20. Weinberg LE, Kunos CA, Zanotti KM (2013) Lymphovascular space invasion (LVSI) is an isolated poor prognostic factor for recurrence and survival among women with intermediate- to high-risk early-stage endometrioid endometrial cancer. Int J Gynecol Cancer 23(8):1438–1445

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bosse T, Peters EE, Creutzberg CL, Jürgenliemk-Schulz IM, Jobsen JJ, Mens JW et al (2015) Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer–A pooled analysis of PORTEC 1 and 2 trials. Eur J Cancer 51(13):1742–1750

    Article  PubMed  Google Scholar 

  22. Slomovit BM, Burk TW, Eife PJ, Ramondetta LM, Silva EG, Jhingran A et al (2003) Uterine papillary serous carcinoma (UPSC): a single institution review of 129 cases. Gynecol Oncol 91(3):463–469

    Article  Google Scholar 

  23. Mittica G, Ghisoni E, Giannone G, Aglietta M, Genta S, Valabrega G (2017) Checkpoint inhibitors in endometrial cancer: preclinical rationale and clinical activity. Oncotarget 8(52):90532–90544

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Prof. Dr. Gulsah Seydaoglu for the help with the statistical analysis of this study.

Funding

This study was supported by the coordination unit of Scientific Research Projects (BAP- TSA-2015–4843) of Çukurova University.

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Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Medicine, Cukurova University, 01330, Saricam/Adana, Turkey

    Umran Kucukgoz Gulec, Ahmet Baris Guzel & Mehmet Ali Vardar

  2. Department of Pathology, Faculty of Medicine, Cukurova University, Adana, Turkey

    Emine Kilic Bagir & Derya Gumurdulu

  3. Department of Medical Oncology, Faculty of Medicine, Cukurova University, Adana, Turkey

    Semra Paydas

Authors
  1. Umran Kucukgoz Gulec
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  2. Emine Kilic Bagir
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  3. Semra Paydas
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  4. Ahmet Baris Guzel
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  5. Derya Gumurdulu
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  6. Mehmet Ali Vardar
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Contributions

UKG: Protocol/project development; data collection or management; data analysis: manuscript writing/editing. EKB: Data collection or management; manuscript writing/editing. SP: Protocol/project development; manuscript writing/editing. ABG: Data collection or management; manuscript writing/editing. DG: Data collection or management; manuscript writing/editing. MAV: Data collection or management; manuscript writing/editing.

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Correspondence to Umran Kucukgoz Gulec.

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Kucukgoz Gulec, U., Kilic Bagir, E., Paydas, S. et al. Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expressions in type 2 endometrial cancer. Arch Gynecol Obstet 300, 377–382 (2019). https://doi.org/10.1007/s00404-019-05180-2

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  • DOI: https://doi.org/10.1007/s00404-019-05180-2

Keywords

  • Programmed death-1 (PD-1)
  • Programmed death-ligand 1 (PD-L1)
  • Prognostic factors
  • Type 2 endometrial cancer
  • Uterine clear cell carcinoma
  • Uterine serous carcinoma
  • Uterine mixed type adenocarcinoma