PMID- 30965283
OWN - NLM
STAT- MEDLINE
DCOM- 20200722
LR  - 20210716
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Print)
IS  - 1351-0088 (Linking)
VI  - 26
IP  - 6
DP  - 2019 Jun
TI  - Papillary thyroid carcinoma behavior: clues in the tumor microenvironment.
PG  - 601-614
LID - 10.1530/ERC-19-0074 [doi]
AB  - The prevalence of thyroid carcinoma is increasing and represents the most common 
      endocrine malignancy, with papillary thyroid carcinoma (PTC) being the most 
      frequent subtype. The genetic alterations identified in PTCs fail to distinguish 
      tumors with different clinical behaviors, such as extra-thyroidal extension and 
      lymph node metastasis. We hypothesize that the immune microenvironment may play a 
      critical role in tumor invasion and metastasis. Computational immunogenomic 
      analysis was performed on 568 PTC samples in The Cancer Genome Atlas using 
      CIBERSORT, TIMER and TIDE deconvolution analytic tools for characterizing immune 
      cell composition. Immune cell infiltrates were correlated with histologic type, 
      mutational type, tumor pathologic T stage and lymph node N stage. Dendritic cells 
      (DCs) are highly associated with more locally advanced tumor T stage (T3/T4, odds 
      ratio (OR) = 2.6, CI = 1.4-4.5, P = 5.4 x 10-4). Increased dendritic cells (OR = 
      3.4, CI = 1.9-6.3, P = 5.5 x 10-5) and neutrophils (OR = 10.5, CI = 2.7-44, P = 
      8.7 x 10-4) significantly correlate with lymph node metastasis. In addition, 
      dendritic cells positively correlate with tall cell morphology (OR = 4.5, CI = 
      1.6-13, P = 4.9 x 10-3) and neutrophils negatively correlate with follicular 
      morphology (OR = 1.3 x 10-3, CI = 5.3 x 10-5-0.031, P = 4.1 x 10-5). TIDE 
      analysis indicates an immune-exclusive phenotype that may be mediated by 
      increased galectin-3 found in PTCs. Thus, characterization of the PTC immune 
      microenvironment using three computational platforms shows that specific immune 
      cells correlate with mutational type, histologic type, local tumor extent and 
      lymph node metastasis. Immunologic evaluation of PTCs may provide a better 
      indication of biologic behavior, resulting in the improved diagnosis and 
      treatment of thyroid cancer.
FAU - Bergdorf, Kensey
AU  - Bergdorf K
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
FAU - Ferguson, Donna C
AU  - Ferguson DC
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
FAU - Mehrad, Mitra
AU  - Mehrad M
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
FAU - Ely, Kim
AU  - Ely K
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
FAU - Stricker, Thomas
AU  - Stricker T
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
FAU - Weiss, Vivian L
AU  - Weiss VL
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee, USA.
LA  - eng
GR  - S10 OD023475/OD/NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
GR  - U24 DK059637/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Lymphocytes, Tumor-Infiltrating/*immunology
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Prognosis
MH  - Thyroid Cancer, Papillary/genetics/immunology/*pathology
MH  - Thyroid Neoplasms/genetics/immunology/*pathology
MH  - Tumor Microenvironment/*genetics/*immunology
MH  - Young Adult
PMC - PMC8279427
MID - NIHMS1712865
OTO - NOTNLM
OT  - RNA sequencing
OT  - immunogenomics
OT  - papillary thyroid carcinoma
OT  - thyroid cancer
OT  - tumor immunology
COIS- Disclosure: No potential conflicts of interest were disclosed by the authors. 
      Declaration of Interest: None of the authors have any conflicts of interest.
EDAT- 2019/04/10 06:00
MHDA- 2020/07/23 06:00
PMCR- 2021/07/14
CRDT- 2019/04/10 06:00
PHST- 2019/04/01 00:00 [received]
PHST- 2019/04/09 00:00 [accepted]
PHST- 2019/04/10 06:00 [pubmed]
PHST- 2020/07/23 06:00 [medline]
PHST- 2019/04/10 06:00 [entrez]
PHST- 2021/07/14 00:00 [pmc-release]
AID - ERC-19-0074.R1 [pii]
AID - 10.1530/ERC-19-0074 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2019 Jun;26(6):601-614. doi: 10.1530/ERC-19-0074.