Endocrinol Metab.  2020 Mar;35(1):44-54. 10.3803/EnM.2020.35.1.44.

Recent Improvements in Genomic and Transcriptomic Understanding of Anaplastic and Poorly Differentiated Thyroid Cancers

Affiliations
  • 1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 2Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
  • 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. yjparkmd@snu.ac.kr
  • 4Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
  • 5Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam, Korea. jeongsunseo@gmail.com
  • 6Gong-Wu Genomic Medicine Institute, Seoul National University Bundang Hospital, Seongnam, Korea.
  • 7Macrogen Inc., Seoul, Korea.

Abstract

Anaplastic thyroid cancer (ATC) is a lethal human cancer with a 5-year survival rate of less than 10%. Recently, its genomic and transcriptomic characteristics have been extensively elucidated over 5 years owing to advance in high throughput sequencing. These efforts have extended molecular understandings into the progression mechanisms and therapeutic vulnerabilities of aggressive thyroid cancers. In this review, we provide an overview of genomic and transcriptomic alterations in ATC and poorly-differentiated thyroid cancer, which are distinguished from differentiated thyroid cancers. Clinically relevant genomic alterations and deregulated signaling pathways will be able to shed light on more effective prevention and stratified therapeutic interventions for affected patients.

Keyword

Thyroid neoplasms; Thyroid carcinoma, anaplastic; Genome; Transcriptome; High-throughput nucleotide sequencing

MeSH Terms

Genome
High-Throughput Nucleotide Sequencing
Humans
Survival Rate
Thyroid Carcinoma, Anaplastic
Thyroid Gland*
Thyroid Neoplasms*
Transcriptome

Figure

  • Fig. 1 The major genetic contributors to thyroid cancer progression. Progression mechanisms of BRAF-positive papillary thyroid cancer (PTC) and RAS-positive follicular thyroid cancer (FTC) are illustrated. TERT, telomerase reverse transcriptase; TP53, tumor protein p53; CDKN2A, cyclin dependent kinase inhibitor 2A; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; AKT1, AKT serine/threonine kinase 1; ATC, anaplastic thyroid cancer; EIF1AX, eukaryotic translation initiation factor 1A X-linked; FA, follicular adenoma; miFTC, minimally invasive FTC; wiFTC, widely invasive FTC.

  • Fig. 2 Transcriptomic signatures of thyroid cancer. (A) Transcriptome based molecular subtype classifications of thyroid cancer according to histological subtypes. From The Cancer Genome Atlas (TCGA)'s original investigation, papillary thyroid cancers are classified into two molecular subtypes, BRAFV600E-like and RAS-like [10]. Afterward, Yoo et al. [11] showed that RAS-like can be breakdown into RAS-like and non-BRAF/non-RAS subtype (NBNR). RAS-like tumors with eukaryotic translation initiation factor 1A X-linked (EIF1AX), paired box 8 (PAX8)-peroxisome proliferator activated receptor gamma (PPARG), and THADA armadillo repeat containing (THADA) fusion were re-classified into NBNR. Dicer 1, ribonuclease III (DICER1), enhancer of zeste 1 polycomb repressive complex 2 subunit (EZH1), isocitrate dehydrogenase (NADP(+)) 1 (IDH1), and speckle type BTB/POZ protein (SPOP) are also associated with NBNR signature. (B) Schematic illustration of activated and deactivated signaling pathways according to the aggressiveness of thyroid cancer. BRS, BRAFV600E-RAS score; MAPK, mitogen-activated protein kinase; ECM, extracellular matrix; PD, programmed death; VEGF, vascular endothelial growth factor; JAK-STAT, Janus kinase-signal transducer and activator of transcription.


Cited by  1 articles

Mechanisms of TERT Reactivation and Its Interaction with BRAFV600E
Young Shin Song, Young Joo Park
Endocrinol Metab. 2020;35(3):515-525.    doi: 10.3803/EnM.2020.304.


Reference

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019; 69:7–34. PMID: 30620402.
Article
2. Dralle H, Machens A, Basa J, Fatourechi V, Franceschi S, Hay ID, et al. Follicular cell-derived thyroid cancer. Nat Rev Dis Primers. 2015; 1:15077. PMID: 27188261.
Article
3. La Vecchia C, Malvezzi M, Bosetti C, Garavello W, Bertuccio P, Levi F, et al. Thyroid cancer mortality and incidence: a global overview. Int J Cancer. 2015; 136:2187–2195. PMID: 25284703.
Article
4. Ibrahimpasic T, Ghossein R, Shah JP, Ganly I. Poorly differentiated carcinoma of the thyroid gland: current status and future prospects. Thyroid. 2019; 29:311–321. PMID: 30747050.
Article
5. Hyman DM, Taylor BS, Baselga J. Implementing genome-driven oncology. Cell. 2017; 168:584–599. PMID: 28187282.
Article
6. Song YS, Park YJ. Genomic characterization of differentiated thyroid carcinoma. Endocrinol Metab (Seoul). 2019; 34:1–10. PMID: 30912334.
Article
7. Bollag G, Tsai J, Zhang J, Zhang C, Ibrahim P, Nolop K, et al. Vemurafenib: the first drug approved for BRAF-mutant cancer. Nat Rev Drug Discov. 2012; 11:873–886. PMID: 23060265.
Article
8. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010; 363:1693–1703. PMID: 20979469.
9. Shaw AT, Friboulet L, Leshchiner I, Gainor JF, Bergqvist S, Brooun A, et al. Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F. N Engl J Med. 2016; 374:54–61. PMID: 26698910.
10. Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014; 159:676–690. PMID: 25417114.
11. Yoo SK, Lee S, Kim SJ, Jee HG, Kim BA, Cho H, et al. Comprehensive analysis of the transcriptional and mutational landscape of follicular and papillary thyroid cancers. PLoS Genet. 2016; 12:e1006239. PMID: 27494611.
Article
12. Mercer KE, Pritchard CA. Raf proteins and cancer: B-Raf is identified as a mutational target. Biochim Biophys Acta. 2003; 1653:25–40. PMID: 12781369.
Article
13. Jung SH, Kim MS, Jung CK, Park HC, Kim SY, Liu J, et al. Mutational burdens and evolutionary ages of thyroid follicular adenoma are comparable to those of follicular carcinoma. Oncotarget. 2016; 7:69638–69648. PMID: 27626165.
Article
14. Yoo SK, Song YS, Lee EK, Hwang J, Kim HH, Jung G, et al. Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer. Nat Commun. 2019; 10:2764. PMID: 31235699.
Article
15. Duan H, Li Y, Hu P, Gao J, Ying J, Xu W, et al. Mutational profiling of poorly differentiated and anaplastic thyroid carcinoma by the use of targeted next-generation sequencing. Histopathology. 2019; 75:890–899. PMID: 31230400.
Article
16. Pozdeyev N, Gay LM, Sokol ES, Hartmaier R, Deaver KE, Davis S, et al. Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. Clin Cancer Res. 2018; 24:3059–3068. PMID: 29615459.
Article
17. Chen H, Luthra R, Routbort MJ, Patel KP, Cabanillas ME, Broaddus RR, et al. Molecular profile of advanced thyroid carcinomas by next-generation sequencing: characterizing tumors beyond diagnosis for targeted therapy. Mol Cancer Ther. 2018; 17:1575–1584. PMID: 29695638.
Article
18. Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest. 2016; 126:1052–1066. PMID: 26878173.
Article
19. Kunstman JW, Juhlin CC, Goh G, Brown TC, Stenman A, Healy JM, et al. Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet. 2015; 24:2318–2329. PMID: 25576899.
Article
20. Khan SA, Ci B, Xie Y, Gerber DE, Beg MS, Sherman SI, et al. Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling. Head Neck. 2019; 41:1928–1934. PMID: 30758123.
Article
21. Tiedje V, Ting S, Herold T, Synoracki S, Latteyer S, Moeller LC, et al. NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma. Oncotarget. 2017; 8:42613–42620. PMID: 28489587.
Article
22. Bonhomme B, Godbert Y, Perot G, Al Ghuzlan A, Bardet S, Belleannee G, et al. Molecular pathology of anaplastic thyroid carcinomas: a retrospective study of 144 cases. Thyroid. 2017; 27:682–692. PMID: 28351340.
Article
23. Jeon MJ, Chun SM, Kim D, Kwon H, Jang EK, Kim TY, et al. Genomic alterations of anaplastic thyroid carcinoma detected by targeted massive parallel sequencing in a BRAF (V600E) mutation-prevalent area. Thyroid. 2016; 26:683–690. PMID: 26980298.
24. Kelly LM, Barila G, Liu P, Evdokimova VN, Trivedi S, Panebianco F, et al. Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer. Proc Natl Acad Sci U S A. 2014; 111:4233–4238. PMID: 24613930.
Article
25. Panebianco F, Nikitski AV, Nikiforova MN, Kaya C, Yip L, Condello V, et al. Characterization of thyroid cancer driven by known and novel ALK fusions. Endocr Relat Cancer. 2019; 26:803–814. PMID: 31539879.
Article
26. Nikitski AV, Rominski SL, Wankhede M, Kelly LM, Panebianco F, Barila G, et al. Mouse model of poorly differentiated thyroid carcinoma driven by STRN-ALK fusion. Am J Pathol. 2018; 188:2653–2661. PMID: 30125543.
Article
27. Landa I, Pozdeyev N, Korch C, Marlow LA, Smallridge RC, Copland JA, et al. Comprehensive genetic characterization of human thyroid cancer cell lines: a validated panel for preclinical studies. Clin Cancer Res. 2019; 25:3141–3151. PMID: 30737244.
Article
28. Martin M, Masshofer L, Temming P, Rahmann S, Metz C, Bornfeld N, et al. Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3. Nat Genet. 2013; 45:933–936. PMID: 23793026.
Article
29. Robertson AG, Shih J, Yau C, Gibb EA, Oba J, Mungall KL, et al. Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell. 2017; 32:204–220. PMID: 28810145.
Article
30. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012; 2:401–404. PMID: 22588877.
31. Yu C, Luo C, Qu B, Khudhair N, Gu X, Zang Y, et al. Molecular network including eIF1AX, RPS7, and 14-3-3γ regulates protein translation and cell proliferation in bovine mammary epithelial cells. Arch Biochem Biophys. 2014; 564:142–155. PMID: 25281768.
Article
32. Krishnamoorthy GP, Davidson NR, Leach SD, Zhao Z, Lowe SW, Lee G, et al. EIF1AX and RAS mutations cooperate to drive thyroid tumorigenesis through ATF4 and c-MYC. Cancer Discov. 2019; 9:264–281. PMID: 30305285.
Article
33. Dienstmann R, Rodon J, Serra V, Tabernero J. Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors. Mol Cancer Ther. 2014; 13:1021–1031. PMID: 24748656.
Article
34. Millis SZ, Ikeda S, Reddy S, Gatalica Z, Kurzrock R. Landscape of phosphatidylinositol-3-kinase pathway alterations across 19 784 diverse solid tumors. JAMA Oncol. 2016; 2:1565–1573. PMID: 27388585.
35. Chaft JE, Arcila ME, Paik PK, Lau C, Riely GJ, Pietanza MC, et al. Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling. Mol Cancer Ther. 2012; 11:485–491. PMID: 22135231.
Article
36. Janku F, Lee JJ, Tsimberidou AM, Hong DS, Naing A, Falchook GS, et al. PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers. PLoS One. 2011; 6:e22769. PMID: 21829508.
Article
37. Chiu JW, Krzyzanowska MK, Serra S, Knox JJ, Dhani NC, Mackay H, et al. Molecular profiling of patients with advanced colorectal cancer: princess margaret cancer centre experience. Clin Colorectal Cancer. 2018; 17:73–79. PMID: 29128266.
Article
38. Gibson WJ, Ruan DT, Paulson VA, Barletta JA, Hanna GJ, Kraft S, et al. Genomic heterogeneity and exceptional response to dual pathway inhibition in anaplastic thyroid cancer. Clin Cancer Res. 2017; 23:2367–2373. PMID: 27797976.
Article
39. Rudolph M, Anzeneder T, Schulz A, Beckmann G, Byrne AT, Jeffers M, et al. AKT1 (E17K) mutation profiling in breast cancer: prevalence, concurrent oncogenic alterations, and blood-based detection. BMC Cancer. 2016; 16:622. PMID: 27515171.
Article
40. Bleeker FE, Felicioni L, Buttitta F, Lamba S, Cardone L, Rodolfo M, et al. AKT1(E17K) in human solid tumours. Oncogene. 2008; 27:5648–5650. PMID: 18504432.
Article
41. Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM, et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature. 2007; 448:439–444. PMID: 17611497.
42. Porta C, Paglino C, Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol. 2014; 4:64. PMID: 24782981.
Article
43. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100:57–70. PMID: 10647931.
Article
44. Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017; 23:703–713. PMID: 28481359.
45. Xing M, Liu R, Liu X, Murugan AK, Zhu G, Zeiger MA, et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014; 32:2718–2726. PMID: 25024077.
Article
46. Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, et al. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2014; 99:E754–E765. PMID: 24476079.
Article
47. Song YS, Lim JA, Choi H, Won JK, Moon JH, Cho SW, et al. Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients. Cancer. 2016; 122:1370–1379. PMID: 26969876.
48. Liu R, Zhang T, Zhu G, Xing M. Regulation of mutant TERT by BRAF V600E/MAP kinase pathway through FOS/GABP in human cancer. Nat Commun. 2018; 9:579. PMID: 29422527.
Article
49. Song YS, Yoo SK, Kim HH, Jung G, Oh AR, Cha JY, et al. Interaction of BRAF-induced ETS factors with mutant TERT promoter in papillary thyroid cancer. Endocr Relat Cancer. 2019; 26:629–641. PMID: 30999281.
Article
50. Diplas BH, He X, Brosnan-Cashman JA, Liu H, Chen LH, Wang Z, et al. The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma. Nat Commun. 2018; 9:2087. PMID: 29802247.
Article
51. Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, et al. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Nat Genet. 2015; 47:1411–1414. PMID: 26523776.
Article
52. Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, et al. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature. 2015; 526:700–704. PMID: 26466568.
Article
53. Liang WS, Hendricks W, Kiefer J, Schmidt J, Sekar S, Carpten J, et al. Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma. Genome Res. 2017; 27:524–532. PMID: 28373299.
Article
54. Donehower LA, Soussi T, Korkut A, Liu Y, Schultz A, Cardenas M, et al. Integrated analysis of TP53 gene and pathway alterations in the Cancer Genome Atlas. Cell Rep. 2019; 28:1370–1384. PMID: 31365877.
Article
55. Cho SY, Park C, Na D, Han JY, Lee J, Park OK, et al. High prevalence of TP53 mutations is associated with poor survival and an EMT signature in gliosarcoma patients. Exp Mol Med. 2017; 49:e317. PMID: 28408749.
Article
56. Muller PA, Vousden KH. Mutant p53 in cancer: new functions and therapeutic opportunities. Cancer Cell. 2014; 25:304–317. PMID: 24651012.
Article
57. Acin S, Li Z, Mejia O, Roop DR, El-Naggar AK, Caulin C. Gain-of-function mutant p53 but not p53 deletion promotes head and neck cancer progression in response to oncogenic K-ras. J Pathol. 2011; 225:479–489. PMID: 21952947.
Article
58. McFadden DG, Vernon A, Santiago PM, Martinez-McFaline R, Bhutkar A, Crowley DM, et al. p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer. Proc Natl Acad Sci U S A. 2014; 111:E1600–E1609. PMID: 24711431.
Article
59. Liggett WH Jr, Sidransky D. Role of the p16 tumor suppressor gene in cancer. J Clin Oncol. 1998; 16:1197–1206. PMID: 9508208.
Article
60. Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012; 489:519–525. PMID: 22960745.
61. Bui NQ, Przybyl J, Trabucco SE, Frampton G, Hastie T, van de Rijn M, et al. A clinico-genomic analysis of soft tissue sarcoma patients reveals CDKN2A deletion as a biomarker for poor prognosis. Clin Sarcoma Res. 2019; 9:12. PMID: 31528332.
Article
62. Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E, Gagnon A, et al. The genetic evolution of melanoma from precursor lesions. N Engl J Med. 2015; 373:1926–1936. PMID: 26559571.
Article
63. Chen S, Sanjana NE, Zheng K, Shalem O, Lee K, Shi X, et al. Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell. 2015; 160:1246–1260. PMID: 25748654.
Article
64. Ravi N, Yang M, Gretarsson S, Jansson C, Mylona N, Sydow SR, et al. Identification of targetable lesions in anaplastic thyroid cancer by genome profiling. Cancers (Basel). 2019; 11:E402. PMID: 30909364.
Article
65. Paulsson JO, Backman S, Wang N, Stenman A, Crona J, Thutkawkorapin J, et al. Whole-genome sequencing of synchronous thyroid carcinomas identifies aberrant DNA repair in thyroid cancer dedifferentiation. J Pathol. 2020; 250:183–194. PMID: 31621921.
Article
66. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017; 357:409–413. PMID: 28596308.
67. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology: mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348:124–128. PMID: 25765070.
68. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015; 372:2509–2520. PMID: 26028255.
69. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014; 371:2189–2199. PMID: 25409260.
Article
70. Wang S, Jia M, He Z, Liu XS. APOBEC3B and APOBEC mutational signature as potential predictive markers for immunotherapy response in non-small cell lung cancer. Oncogene. 2018; 37:3924–3936. PMID: 29695832.
Article
71. Faden DL, Ding F, Lin Y, Zhai S, Kuo F, Chan TA, et al. APOBEC mutagenesis is tightly linked to the immune landscape and immunotherapy biomarkers in head and neck squamous cell carcinoma. Oral Oncol. 2019; 96:140–147. PMID: 31422205.
Article
72. Kasaian K, Wiseman SM, Walker BA, Schein JE, Zhao Y, Hirst M, et al. The genomic and transcriptomic landscape of anaplastic thyroid cancer: implications for therapy. BMC Cancer. 2015; 15:984. PMID: 26680454.
Article
73. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013; 14:1014–1022. PMID: 24048123.
Article
74. Kim K, Jeon S, Kim TM, Jung CK. Immune gene signature delineates a subclass of papillary thyroid cancer with unfavorable clinical outcomes. Cancers (Basel). 2018; 10:E494. PMID: 30563160.
Article
75. Coates PJ, Rundle JK, Lorimore SA, Wright EG. Indirect macrophage responses to ionizing radiation: implications for genotype-dependent bystander signaling. Cancer Res. 2008; 68:450–456. PMID: 18199539.
Article
76. Giannini R, Moretti S, Ugolini C, Macerola E, Menicali E, Nucci N, et al. Immune profiling of thyroid carcinomas suggests the existence of two major phenotypes: an ATC-like and a PDTC-like. J Clin Endocrinol Metab. 2019; 104:3557–3575. PMID: 30882858.
Article
77. Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019; 18:197–218. PMID: 30610226.
Article
78. Cantara S, Bertelli E, Occhini R, Regoli M, Brilli L, Pacini F, et al. Blockade of the programmed death ligand 1 (PD-L1) as potential therapy for anaplastic thyroid cancer. Endocrine. 2019; 64:122–129. PMID: 30762153.
Article
79. Chintakuntlawar AV, Rumilla KM, Smith CY, Jenkins SM, Foote RL, Kasperbauer JL, et al. Expression of PD-1 and PD-L1 in anaplastic thyroid cancer patients treated with multimodal therapy: results from a retrospective study. J Clin Endocrinol Metab. 2017; 102:1943–1950. PMID: 28324060.
Article
80. Ahn S, Kim TH, Kim SW, Ki CS, Jang HW, Kim JS, et al. Comprehensive screening for PD-L1 expression in thyroid cancer. Endocr Relat Cancer. 2017; 24:97–106. PMID: 28093480.
Article
81. Bastman JJ, Serracino HS, Zhu Y, Koenig MR, Mateescu V, Sams SB, et al. Tumor-infiltrating T cells and the PD-1 checkpoint pathway in advanced differentiated and anaplastic thyroid cancer. J Clin Endocrinol Metab. 2016; 101:2863–2873. PMID: 27045886.
Article
82. Havel JJ, Chowell D, Chan TA. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer. 2019; 19:133–150. PMID: 30755690.
Article
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