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

Research output: Contribution to journalArticle

Abstract

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 the 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 t hat 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.

Original languageEnglish
Pages (from-to)139-149
Number of pages11
JournalEuropean Journal of Endocrinology
Volume181
Issue number2
DOIs
Publication statusPublished - 2019 Jan 1

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Epithelial-Mesenchymal Transition
Neoplasms
Papillary Thyroid Microcarcinoma
Lymph Nodes
Odds Ratio
Neoplasm Metastasis
Genes
Factor IX
Laminin
Vimentin
Cadherins
Transcriptome
Ultrasonography
Thyroid Gland
Up-Regulation
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Lee, Woo Kyung ; Lee, Jandee ; Kim, Hyunji ; Lee, Seul Gi ; Choi, Sun Hyung ; Jeong, Seonhyang ; Kwon, Hyeong Ju ; Jung, Sang Geun ; Jo, Young Suk. / Peripheral location and infiltrative margin predict invasive features of papillary thyroid microcarcinoma. In: European Journal of Endocrinology. 2019 ; Vol. 181, No. 2. pp. 139-149.
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abstract = "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 the 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 t hat 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.",
author = "Lee, {Woo Kyung} and Jandee Lee and Hyunji Kim and Lee, {Seul Gi} and Choi, {Sun Hyung} and Seonhyang Jeong and Kwon, {Hyeong Ju} and Jung, {Sang Geun} and Jo, {Young Suk}",
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Peripheral location and infiltrative margin predict invasive features of papillary thyroid microcarcinoma. / Lee, Woo Kyung; Lee, Jandee; Kim, Hyunji; Lee, Seul Gi; Choi, Sun Hyung; Jeong, Seonhyang; Kwon, Hyeong Ju; Jung, Sang Geun; Jo, Young Suk.

In: European Journal of Endocrinology, Vol. 181, No. 2, 01.01.2019, p. 139-149.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Peripheral location and infiltrative margin predict invasive features of papillary thyroid microcarcinoma

AU - Lee, Woo Kyung

AU - Lee, Jandee

AU - Kim, Hyunji

AU - Lee, Seul Gi

AU - Choi, Sun Hyung

AU - Jeong, Seonhyang

AU - Kwon, Hyeong Ju

AU - Jung, Sang Geun

AU - Jo, Young Suk

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 the 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 t hat 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.

AB - 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 the 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 t hat 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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