Tumor immune microenvironment characteristics of papillary thyroid carcinoma are associated with histopathological aggressiveness and BRAF mutation status

Casey Means, Daniel Clayburgh, Lauren Maloney, David Sauer, Matthew H. Taylor, Maisie Shindo, Lisa Coussens, Takahiro Tsujikawa

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Abstract

Background: Papillary thyroid carcinoma (PTC) follows an indolent course; however, up to 30% of patients develop recurrent disease requiring further treatment. Profiling PTC immune complexity may provide new biomarkers for improved risk prediction. Methods: Immune complexity profiles were quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 39 patients with PTC, and were assessed for correlations with aggressive histopathological features based on the presence of lymphovascular invasion and/or extrathyroidal extension, and BRAF V600E mutational status. Results: mIHC revealed two distinct immune clusters stratifying patients: a lymphoid-inflamed group (higher CD8 + T cells, reduced dendritic and mast cells) and a myeloid/hypo-inflamed group that correlated with aggressive pathological features. BRAF mutation was not associated with aggressive pathological features but did correlate with increased mast cell density. Conclusions: Distinct immune microenvironments exist in PTC correlating with pathological aggressiveness. Immune-based biomarkers associated with possible tumor-immune interactions may be used for risk stratification.

Original languageEnglish (US)
JournalHead and Neck
DOIs
StatePublished - Jan 1 2019

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Tumor Microenvironment
Mutation
Mast Cells
Biomarkers
Immunohistochemistry
Dendritic Cells
Cell Count
T-Lymphocytes
Papillary Thyroid cancer
Neoplasms
Therapeutics

Keywords

  • biomarker
  • immune cell
  • multiplex immunohistochemistry
  • thyroid cancer
  • tumor microenvironment

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

@article{f06ba7620dec4a4caf30d857c7179f73,
title = "Tumor immune microenvironment characteristics of papillary thyroid carcinoma are associated with histopathological aggressiveness and BRAF mutation status",
abstract = "Background: Papillary thyroid carcinoma (PTC) follows an indolent course; however, up to 30{\%} of patients develop recurrent disease requiring further treatment. Profiling PTC immune complexity may provide new biomarkers for improved risk prediction. Methods: Immune complexity profiles were quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 39 patients with PTC, and were assessed for correlations with aggressive histopathological features based on the presence of lymphovascular invasion and/or extrathyroidal extension, and BRAF V600E mutational status. Results: mIHC revealed two distinct immune clusters stratifying patients: a lymphoid-inflamed group (higher CD8 + T cells, reduced dendritic and mast cells) and a myeloid/hypo-inflamed group that correlated with aggressive pathological features. BRAF mutation was not associated with aggressive pathological features but did correlate with increased mast cell density. Conclusions: Distinct immune microenvironments exist in PTC correlating with pathological aggressiveness. Immune-based biomarkers associated with possible tumor-immune interactions may be used for risk stratification.",
keywords = "biomarker, immune cell, multiplex immunohistochemistry, thyroid cancer, tumor microenvironment",
author = "Casey Means and Daniel Clayburgh and Lauren Maloney and David Sauer and Taylor, {Matthew H.} and Maisie Shindo and Lisa Coussens and Takahiro Tsujikawa",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/hed.25740",
language = "English (US)",
journal = "Head and Neck",
issn = "1043-3074",
publisher = "Wiley-Liss Inc.",

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TY - JOUR

T1 - Tumor immune microenvironment characteristics of papillary thyroid carcinoma are associated with histopathological aggressiveness and BRAF mutation status

AU - Means, Casey

AU - Clayburgh, Daniel

AU - Maloney, Lauren

AU - Sauer, David

AU - Taylor, Matthew H.

AU - Shindo, Maisie

AU - Coussens, Lisa

AU - Tsujikawa, Takahiro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Papillary thyroid carcinoma (PTC) follows an indolent course; however, up to 30% of patients develop recurrent disease requiring further treatment. Profiling PTC immune complexity may provide new biomarkers for improved risk prediction. Methods: Immune complexity profiles were quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 39 patients with PTC, and were assessed for correlations with aggressive histopathological features based on the presence of lymphovascular invasion and/or extrathyroidal extension, and BRAF V600E mutational status. Results: mIHC revealed two distinct immune clusters stratifying patients: a lymphoid-inflamed group (higher CD8 + T cells, reduced dendritic and mast cells) and a myeloid/hypo-inflamed group that correlated with aggressive pathological features. BRAF mutation was not associated with aggressive pathological features but did correlate with increased mast cell density. Conclusions: Distinct immune microenvironments exist in PTC correlating with pathological aggressiveness. Immune-based biomarkers associated with possible tumor-immune interactions may be used for risk stratification.

AB - Background: Papillary thyroid carcinoma (PTC) follows an indolent course; however, up to 30% of patients develop recurrent disease requiring further treatment. Profiling PTC immune complexity may provide new biomarkers for improved risk prediction. Methods: Immune complexity profiles were quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 39 patients with PTC, and were assessed for correlations with aggressive histopathological features based on the presence of lymphovascular invasion and/or extrathyroidal extension, and BRAF V600E mutational status. Results: mIHC revealed two distinct immune clusters stratifying patients: a lymphoid-inflamed group (higher CD8 + T cells, reduced dendritic and mast cells) and a myeloid/hypo-inflamed group that correlated with aggressive pathological features. BRAF mutation was not associated with aggressive pathological features but did correlate with increased mast cell density. Conclusions: Distinct immune microenvironments exist in PTC correlating with pathological aggressiveness. Immune-based biomarkers associated with possible tumor-immune interactions may be used for risk stratification.

KW - biomarker

KW - immune cell

KW - multiplex immunohistochemistry

KW - thyroid cancer

KW - tumor microenvironment

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