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Prolonged survival of anaplastic thyroid carcinoma is associated with resectability, low tumor-infiltrating neutrophils/myeloid-derived suppressor cells, and low peripheral neutrophil-to-lymphocyte ratio

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Abstract

Purpose

Anaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid cancer with most patients dying of their disease within a few months. Only a very small percentage of long-term survivors (LTS) are alive for 2 years or longer. In this retrospective case-control study, we provided a comprehensive comparison between 46 ATC LTSs and 75 ATC control patients who suffered disease-specific mortality within 2 years, aiming to identify factors that may be associated with prolonged survival in ATC.

Methods

A comprehensive clinicopathologic and molecular comparison was performed between 46 ATC LTSs and 75 ATC control patients. Peripheral neutrophil count and neutrophil-to-lymphocyte ratio (NLR) were recorded. The composition of the tumor microenvironment was compared using immunohistochemistry.

Results

Compared with ATC control patients, ATC LTSs were characterized by 1) higher frequency of (primary) resection as well as clinicopathologic parameters attributed to resectability; 2) lower rate of concurrent RAS/BRAF and TERT promoter mutations; 3) lower peripheral neutrophil count and NLR; and 4) lower number of tumor-infiltrating neutrophils/myeloid-derived suppressor cells (MDSC). The survival benefits of low peripheral neutrophil counts and low NLR persisted even when controlling for distant metastasis status at presentation.

Conclusions

In addition to traditional beneficial prognostic factors, e.g., surgical resection, factors attributed to resectability, and absence of co-existing RAS/BRAF and TERT promoter mutations, we herein show that tumor-infiltrating and circulating neutrophils/MDSC are adverse prognostic factors in ATC.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. B. Lin, H. Ma, M. Ma, Z. Zhang, Z. Sun et al. The incidence and survival analysis for anaplastic thyroid cancer: a SEER database analysis. Am J. Transl. Res. 11, 5888–5896 (2019)

    PubMed  PubMed Central  Google Scholar 

  2. T.A. Janz, D.M. Neskey, S.A. Nguyen, E.J. Lentsch, Is the incidence of anaplastic thyroid cancer increasing: a population based epidemiology study. World J. Otorhinolaryngol. Head. Neck Surg. 5, 34–40 (2019)

    Article  Google Scholar 

  3. N. Prasongsook, A. Kumar, A.V. Chintakuntlawar, R.L. Foote, J. Kasperbauer et al. Survival in response to multimodal therapy in anaplastic thyroid cancer. J. Clin. Endocrinol. Metab. 102, 4506–4514 (2017)

    Article  Google Scholar 

  4. B. Xu, T. Fuchs, S. Dogan, I. Landa, N. Katabi et al. Dissecting anaplastic thyroid carcinoma: a comprehensive clinical, histologic, immunophenotypic, and molecular study of 360 cases. Thyroid 30, 1505–1517 (2020)

    Article  CAS  Google Scholar 

  5. A. Mohebati, M. Dilorenzo, F. Palmer, S.G. Patel, D. Pfister et al. Anaplastic thyroid carcinoma: a 25-year single-institution experience. Ann. Surg. Oncol. 21, 1665–1670 (2014)

    Article  CAS  Google Scholar 

  6. G.B. Hvilsom, S.C. Londero, C.H. Hahn, S. Schytte, H.B. Pedersen et al. Anaplastic thyroid carcinoma in Denmark 1996-2012: a national prospective study of 219 patients. Cancer Epidemiol. 53, 65–71 (2018)

    Article  Google Scholar 

  7. J. Wendler, M. Kroiss, K. Gast, M.C. Kreissl, S. Allelein et al. Clinical presentation, treatment and outcome of anaplastic thyroid carcinoma: results of a multicenter study in Germany. Eur. J. Endocrinol./Eur. Federation Endocr. Soc. 175, 521–529 (2016)

    Article  CAS  Google Scholar 

  8. I. Sugitani, A. Miyauchi, K. Sugino, T. Okamoto, A. Yoshida et al. Prognostic factors and treatment outcomes for anaplastic thyroid carcinoma: ATC Research Consortium of Japan cohort study of 677 patients. World J. Surg. 36, 1247–1254 (2012)

    Article  Google Scholar 

  9. K. Kos, K.E. de Visser, Neutrophils create a fertile soil for metastasis. Cancer Cell 39, 301–303 (2021)

    Article  CAS  Google Scholar 

  10. K. Cole, K. Pravoverov, J.E. Talmadge, Role of myeloid-derived suppressor cells in metastasis. Cancer Metastasis Rev. 40, 391–411 (2021)

    Article  Google Scholar 

  11. M. Wu, M. Ma, Z. Tan, H. Zheng, X. Liu, Neutrophil: a new player in metastatic cancers. Front. Immunol. 11, 565165 (2020)

    Article  CAS  Google Scholar 

  12. R. Trovato, S. Cane, V. Petrova, S. Sartoris, S. Ugel et al. The engagement between MDSCs and metastases: partners in crime. Front. Oncol. 10, 165 (2020)

    Article  Google Scholar 

  13. A.M.K. Law, F. Valdes-Mora, D. Gallego-Ortega, Myeloid-derived suppressor cells as a therapeutic target for cancer. Cells 9, 561 (2020).

    Article  CAS  Google Scholar 

  14. M. Shen, P. Hu, F. Donskov, G. Wang, Q. Liu et al. Tumor-associated neutrophils as a new prognostic factor in cancer: a systematic review and meta-analysis. PloS One 9, e98259 (2014)

    Article  Google Scholar 

  15. C. Valero, M. Lee, D. Hoen, K. Weiss, D.W. Kelly et al. Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors. Nat. Commun. 12, 729 (2021)

    Article  CAS  Google Scholar 

  16. T. Sato, M. Omura, J. Saito, A. Hirasawa, Y. Kakuta et al. Neutrophilia associated with anaplastic carcinoma of the thyroid: production of macrophage colony-stimulating factor (M-CSF) and interleukin-6. Thyroid 10, 1113–1118 (2000)

    Article  CAS  Google Scholar 

  17. J. Park, J. Park, J.H. Shin, Y.L. Oh, H.A. Jung, et al. Prognostic value of the neutrophil-to-lymphocyte ratio before and after radiotherapy for anaplastic thyroid carcinoma. Cancers 13 13, 1913 (2021).

    Article  CAS  Google Scholar 

  18. N. Fukuda, K. Toda, Y.U. Fujiwara, X. Wang, A. Ohmoto et al. Neutrophil-to-lymphocyte ratio as a prognostic marker for anaplastic thyroid cancer treated with lenvatinib. In vivo 34, 2859–2864 (2020)

    Article  CAS  Google Scholar 

  19. D.T. Cheng, T.N. Mitchell, A. Zehir, R.H. Shah, R. Benayed et al. Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J. Mol. Diagn. 17, 251–264 (2015)

    Article  CAS  Google Scholar 

  20. A.J. Gentles, A.M. Newman, C.L. Liu, S.V. Bratman, W. Feng et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat. Med. 21, 938–945 (2015)

    Article  CAS  Google Scholar 

  21. M. Ryder, R.A. Ghossein, J.C. Ricarte-Filho, J.A. Knauf, J.A. Fagin, Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer. Endocr.-Relat. Cancer 15, 1069–1074 (2008)

    Article  CAS  Google Scholar 

  22. I. Landa, T. Ibrahimpasic, L. Boucai, R. Sinha, J.A. Knauf et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J. Clin. Investig. 126, 1052–1066 (2016)

    Article  Google Scholar 

  23. G.Q. Zhang, W.J. Wei, H.J. Song, Z.K. Sun, C.T. Shen et al. Programmed cell death-ligand 1 overexpression in thyroid cancer. Endocr. Pract. 25, 279–286 (2019)

    Article  Google Scholar 

  24. S. Cameselle-Garcia, S. Abdulkader-Sande, M. Sanchez-Ares, G. Rodriguez-Carnero, J. Garcia-Gomez et al. PD-L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: a retrospective study. Oncol. Lett. 22, 553 (2021)

    Article  CAS  Google Scholar 

  25. I. Girolami, L. Pantanowitz, O. Mete, M. Brunelli, S. Marletta et al. Programmed death-ligand 1 (PD-L1) is a potential biomarker of disease-free survival in papillary thyroid carcinoma: a systematic review and meta-analysis of PD-L1 immunoexpression in follicular epithelial derived thyroid carcinoma. Endocr. Pathol. 31, 291–300 (2020)

    Article  CAS  Google Scholar 

  26. J. Capdevila, L.J. Wirth, T. Ernst, S. Ponce Aix, C.C. Lin et al. PD-1 blockade in anaplastic thyroid carcinoma. J. Clin. Oncol. 38, 2620–2627 (2020)

    Article  CAS  Google Scholar 

  27. G. Al-Khadairi, J. Decock, Cancer testis antigens and immunotherapy: where do we stand in the targeting of PRAME? Cancers 11, 984 (2019).

    Article  CAS  Google Scholar 

  28. J. Li, J. Yin, J. Zhong, Z. Yang, A. Tang et al. Clinicopathological and prognostic significance of PRAME overexpression in human cancer: a meta-analysis. BioMed. Res. Int. 2020, 8828579 (2020)

    PubMed  PubMed Central  Google Scholar 

  29. K. Dhatchinamoorthy, J.D. Colbert, K.L. Rock, Cancer immune evasion through loss of MHC class I antigen presentation. Front. Immunol. 12, 636568 (2021)

    Article  CAS  Google Scholar 

  30. S.M. Glaser, S.F. Mandish, B.S. Gill, G.K. Balasubramani, D.A. Clump et al. Anaplastic thyroid cancer: prognostic factors, patterns of care, and overall survival. Head Neck 38(Suppl 1), E2083–E2090 (2016)

    Article  Google Scholar 

Download references

Funding

Research reported in this publication was supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748 and a departmental RFA funded by PaigeAI (SK202-1328).

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Bin Xu, Abhinita S. Mohanty, Snjezana Dogan & Ronald Ghossein

  2. Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada

    Lingxin Zhang

  3. Department of Pathology, Cedar Sinai Medical Center, Los Angeles, CA, USA

    Reza Setoodeh & Bonnie Balzer

  4. Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA

    Iñigo Landa

  5. Division of Subspecialty Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Vera Tiedje & James A. Fagin

  6. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Ian Ganly

Authors
  1. Bin Xu
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  2. Lingxin Zhang
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  3. Reza Setoodeh
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  4. Abhinita S. Mohanty
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  5. Iñigo Landa
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  7. Vera Tiedje
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  8. Ian Ganly
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  10. James A. Fagin
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  11. Ronald Ghossein
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Contributions

Study design: B.X., R.G. Pathology and clinical reviews: B.X., L.X., R.S., I.G., B.B. Molecular analysis: B.X., A.M., I.L., J.A.F. Immunohistochemistry: B.X., V.T. Manuscript drafting: B.X., R.G. Manuscript editing: All authors.

Corresponding author

Correspondence to Bin Xu.

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No competing financial interests exist for all contributory authors. All of the research meets the ethics guidelines, including adherence to the legal requirements of the country where the study was performed.

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Xu, B., Zhang, L., Setoodeh, R. et al. Prolonged survival of anaplastic thyroid carcinoma is associated with resectability, low tumor-infiltrating neutrophils/myeloid-derived suppressor cells, and low peripheral neutrophil-to-lymphocyte ratio. Endocrine 76, 612–619 (2022). https://doi.org/10.1007/s12020-022-03008-9

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  • DOI: https://doi.org/10.1007/s12020-022-03008-9

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