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Peripheral location and infiltrative margin predict invasive features of papillary thyroid microcarcinoma

 Woo Kyung Lee  ;  Jandee Lee  ;  Hyunji Kim  ;  Seul Gi Lee  ;  Sun Hyung Choi  ;  Seonhyang Jeong  ;  Hyeong Ju Kwon  ;  Sang Geun Jung  ;  Young Suk Jo 
 EUROPEAN JOURNAL OF ENDOCRINOLOGY, Vol.181(2) : 139-149, 2019 
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OBJECTIVE: Tumor location in papillary thyroid microcarcinoma (PTMC) might determine tumor outgrowth from the thyroid gland. However, the clinical implications of tumor location and minimal extrathyroid extension (mETE) have not been well-elucidated. We aimed to investigate the relationship between tumor location and mETE to predict aggressiveness of PTMC. METHODS: A total of 858 patients with PTMC were grouped according to tumor location on ultrasonography: central (cPTMC) and peripheral PTMC (pPTMC). PTMC without mETE (PTMC-mETE(-)) was divided further according to margin shape: encapsulated (E-) or infiltrative (I-). To understand the molecular biologic characteristics of PTMC presenting with an I-margin and mETE, transcriptome data from TCGA-THCA were analyzed using Gene Set Enrichment Analysis (GSEA). RESULTS: pPTMC (n=807, 94.1%) accounted for the majority of cases; mETE was identified only in pPTMC (403/807; 49.9%). pPTMC-mETE(+) showed aggressive clinical characteristics that increased the odds ratio (OR) for lymph node metastasis (LNM). Interestingly, subgroup analysis of PTMC-mETE(-) revealed that the I-margin also increased the OR for LNM, independent of other clinical factors. GSEA of TCGA-THCA data suggested coordinated upregulation of genes related to epithelial-mesenchymal transition (EMT) in PTC with mETE. Immunohistochemical staining for Laminin Subunit Gamma 2 (LAMC2), CD59, E-cadherin, and vimentin showed that these markers of EMT were associated with progressive changes in E-margin PTMC-mETE(-), I-margin PTMC-mETE(-), and pPTMC-mETE(+). CONCLUSION: mETE related to peripheral location of PTMC is an important predictor of tumor invasiveness, as is the I-margin, which presents with EMT features similar to mETE. I-margin PTMC-mETE(-) and pPTMC-mETE(+) might reflect the pattern of invasive PTMC.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jan Dee(이잔디) ORCID logo https://orcid.org/0000-0003-4090-0049
Jo, Young Suk(조영석) ORCID logo https://orcid.org/0000-0001-9926-8389
Choi, S.H.(최선형)
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