Skip to main content

Advertisement

SpringerLink
Log in

PD-L1 expression in tongue squamous cell carcinoma

  • Original Paper
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

A Correction to this article was published on 14 December 2020

This article has been updated

Abstract

Purpose

Immune checkpoint proteins programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important therapeutic targets for head and neck cancer. This large-scale case study aimed to analyze tongue squamous cell carcinomas (SCCs) and evaluate the correlation between PD-L1 expression and clinical prognosis. So far, this study is the largest case study on PD-L1 expression in tongue SCCs.

Methods

This is a case–control study that analyzed 121 tongue SCCs. Paraffin-embedded sections and clinical data were obtained retrospectively and immunohistochemistry with PD-L1 was performed.

Results

11.6% contained ≥ 50% of PD-L1-positive cells, 57.1% of these cases had a poor prognosis with nodal metastasis. Among cases of T1/2 primary lesions with nodal metastasis, cases of high PD-L1 expression had a significantly shorter disease-free survival than cases of no PD-L1 expression (p = 0.018). The hazard ratio for high PD-L1 expression was 3.21 (95 per cent CI, 1.26–8.72) compared with no PD-L1 expression after adjusting for other factors.

Conclusions

These data indicate that PD-L1 upregulation in tongue SCCs is associated with a more advanced stage and shorter disease-free survival. PD-1/PD-L1 inhibitors might hence constitute potential adjuvant therapy for tongue SCCs with PD-L1 upregulation.

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
Fig. 4

Similar content being viewed by others

Change history

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

    Article  CAS  Google Scholar 

  2. Pfister DG, Ang K, Brockstein B, Colevas AD, Ellenhorn J, Goepfert H, Hicks WL, Hong WK, Kies MS, Lydiatt W, McCaffrey T, Mittal BB, Ridge JA, Schuller DE, Shah JP, Spencer S, Trotti A, Urba S, Weymuller EA, Wheeler RH, Wolf GT (2000) NCCN practice guidelines for head and neck cancers. Oncology 14:163–194

    CAS  PubMed  Google Scholar 

  3. Guidi A, Codecà C, Ferrari D (2018) Chemotherapy and immunotherapy for recurrent and metastatic head and neck cancer: a systematic review. Med Oncol 35:37

    Article  Google Scholar 

  4. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359:1116–1127

    Article  CAS  Google Scholar 

  5. Kiyota N, Hasegawa Y, Takahashi S, Yokota T, Yen C-J, Iwae S, Shimizu Y, Hong RL, Goto M, Kang JH, Li WSK, Ferris RL, Gillison M, Namba Y, Monga M, Lynch M, Tahara M (2017) A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator's choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141. Oral Oncol 73:138–146

    Article  CAS  Google Scholar 

  6. Scognamiglio T, Chen Y-T (2018) Beyond the percentages of PD-L1-positive tumor cells: induced versus constitutive PD-L1 expression in primary and metastatic head and neck squamous cell carcinoma. Head Neck Pathol 12:221–229

    Article  Google Scholar 

  7. Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Docampo LCI, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375:1856–1867

    Article  Google Scholar 

  8. O’Sullivan B (2010) International Union Against Cancer (UICC). Lip and oral cavity. In: Sobin LH, Gospo- darowicz MK, Wittekind C (eds) TNM classification of malignant tumours. 7th ed. New York: Wiley; 2010. p. 25–29

  9. Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, Richardson W, Towne P, Hanks D, Vennapusa B, Mistry A, Kalamegham R, Averbuch S, Novotny J, Rubin E, Emancipator K, McCaffery I, Williams JA, Walker J, Longshore J, Tsao MS, Kerr KM (2017) PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project. J Thorac Oncol 12:208–222

    Article  Google Scholar 

  10. Chen SC, Chang PMH, Wang HJ, Tai SK, Chu PY, Yang MH (2018) PD-L1 expression is associated with p16INK4Aexpression in non-oropharyngeal head and neck squamous cell carcinoma. Oncol Lett 15:2259–2265

    PubMed  Google Scholar 

  11. Schneider S, Kadletz L, Wiebringhaus R, Kenner L, Selzer E, Füreder T, Rajky O, Berghoff AS, Preusser M, Heiduschka G (2018) PD-1 and PD-L1 expression in HNSCC primary cancer and related lymph node metastasis - impact on clinical outcome. Histopathology 73:573–584

    Article  Google Scholar 

  12. Satgunaseelan L, Gupta R, Madore J, Chia N, Lum T, Palme CE, Boyer M, Scolyer RA, Clark JR (2016) Programmed cell death-ligand 1 expression in oral squamous cell carcinoma is associated with an inflammatory phenotype. Pathology 48:574–580

    Article  CAS  Google Scholar 

  13. Maruse Y, Kawano S, Jinno T, Matsubara R, Goto Y, Kaneko N, Sakamoto T, Hashiguchi Y, Moriyama M, Toyoshima T, Kitamura R, Tanaka H, Oobu K, Kiyoshima T, Nakamura S (2018) Significant association of increased PD-L1 and PD-1 expression with nodal metastasis and a poor prognosis in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 47:836–845

    Article  CAS  Google Scholar 

  14. Straub M, Drecoll E, Pfarr N, Weichert W, Langer R, Hapfelmeier A, Götz C, Wolff KD, Kolk A, Specht K (2016) CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity. Oncotarget Impact J 7:12024–12034

    Article  Google Scholar 

  15. Bauml J, Seiwert TY, Pfister DG, Worden F, Liu SV, Gilbert J, Saba NF, Weiss J, Wirth L, Sukari A, Kang H, Gibson MK, Massarelli E, Powell S, Meister A, Schu X, Cheng JD, Haddad R (2017) Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study. J Clin Oncol 35:1542–1549

    Article  CAS  Google Scholar 

  16. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L (2015) Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 372:2018–2028

    Article  Google Scholar 

  17. Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim J, Arvis CD, Ahn M, Majem M, Fidler MJ, de Castro G, Garrido M, Lubiniecki GM, ShentuY IME, Dolled Filhart M, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387:1540–1550

    Article  CAS  Google Scholar 

  18. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A et al (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375:1823–1833

    Article  CAS  Google Scholar 

  19. Haratake N, Toyokawa G, Tagawa T, Kozuma Y, Matsubara T, Takamori S, Akamine T, Yamada Y, Oda Y, Maehara Y (2017) Positive conversion of PD-L1 expression after treatments with chemotherapy and nivolumab. Anticancer Res 37:5713–5717

    CAS  PubMed  Google Scholar 

  20. Lin Y, Sung W, Hsieh M, Tsai S, Lai H, Yang S, Chen K, Chen M, Lee H, Yeh K, Chen C (2015) High PD-L1 expression correlates with metastasis and poor prognosis in oral squamous cell carcinoma. Suzuki H, editor. PLoS ONE 10:e0142656

  21. Hanna GJ, Woo SB, Li YY, Barletta JA, Hammerman PS, Lorch JH (2018) Tumor PD-L1 expression is associated with improved survival and lower recurrence risk in young women with oral cavity squamous cell carcinoma. Oral Maxillofacial Surg 47:568–577

    CAS  Google Scholar 

Download references

Acknowledgements

None

Funding

None.

Author information

Authors and Affiliations

  1. Department of Otolaryngology, Okayama Red Cross Hospital, Okayama, 700-8607, Japan

    Naoki Akisada

  2. Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kumamoto University, 1-1-1 Honjo, Kumamoto-City, Kumamoto, 860-8556, Japan

    Kohei Nishimoto & Yorihisa Orita

  3. Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan

    Soshi Takao

  4. Departments of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan

    Yuka Gion, Tomohiro Toji, Tadashi Yoshino & Yasuharu Sato

  5. Departments of Otolaryngology Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, Japan

    Hidenori Marunaka, Takuma Makino, Kentaro Miki, Munechika Tsumura & Kazunori Nishizaki

  6. Department of Otolaryngology, Himeji Red Cross Hospital, Himeji, Hyogo, 670-8540, Japan

    Tomoyasu Tachibana

  7. Departments of Otolaryngology, Okayama Medical Center, Okayama, 701-1192, Japan

    Yusuke Akagi

Authors
  1. Naoki Akisada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kohei Nishimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Soshi Takao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuka Gion
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hidenori Marunaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomoyasu Tachibana
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takuma Makino
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kentaro Miki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yusuke Akagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Munechika Tsumura
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tomohiro Toji
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Tadashi Yoshino
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kazunori Nishizaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yorihisa Orita
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yasuharu Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yorihisa Orita.

Ethics declarations

Conflict of interest

None.

Disclosure statement

All authors declare that: (i) no support, financial or otherwise, has been received from any organization that may have an interest in the submitted work; and (ii) there are no other relationships or activities that could appear to have influenced the submitted work.

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

Akisada, N., Nishimoto, K., Takao, S. et al. PD-L1 expression in tongue squamous cell carcinoma. Med Mol Morphol 54, 52–59 (2021). https://doi.org/10.1007/s00795-020-00261-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-020-00261-7

Keywords

Search

Navigation