J Pathol Transl Med.  2016 Sep;50(5):377-384. 10.4132/jptm.2016.07.25.

Do Helper T Cell Subtypes in Lymphocytic Thyroiditis Play a Role in the Antitumor Effect?

Affiliations
  • 1Department of Medicine, Yonsei University Graduate School, Seoul, Korea.
  • 2Department of Laboratory Medicine, Chosun University College of Medicine, Gwangju, Korea.
  • 3Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
  • 4Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea.
  • 5Department of General Surgery, Yonsei University College of Medicine, Seoul, Korea.
  • 6Department of Pathology, Sungkyunkwan University College of Medicine, Seoul, Korea.
  • 7Department of Pathology, Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, Korea. soonwonh@yuhs.ac

Abstract

BACKGROUND
Papillary thyroid carcinoma (PTC) is frequently accompanied by lymphocytic thyroiditis (LT). Some reports claim that Hashimoto's thyroiditis (the clinical form of LT) enhances the likelihood of PTC; however, others suggest that LT has antitumor activity. This study was aimed to find out the relationship between the patterns of helper T cell (Th) cytokines in thyroid tissue of PTC with or without LT and the clinicopathological manifestation of PTC.
METHODS
Fresh surgical samples of PTC with (13 cases) or without (10 cases) LT were used. The prognostic parameters (tumor size, extra-thyroidal extension of PTC, and lymph node metastasis) were analyzed. The mRNA levels of two subtypes of Th cytokines, Th1 (tumor necrosis factor α [TNF-α], interferon γ [IFN-γ ], and interleukin [IL] 2) and Th2 (IL-4 and IL-10), were analyzed. Because most PTC cases were microcarcinomas and recent cases without clinical follow-up, negative or faint p27 immunoreactivity was used as a surrogate marker for lymph node metastasis.
RESULTS
PTC with LT cases showed significantly higher expression of TNF-α (p = .043), IFN-γ (p < .010), IL-4 (p = .015) than those without LT cases. Although the data were not statistically significant, all analyzed cytokines (except for IL-4) were highly expressed in the cases with higher expression of p27 surrogate marker.
CONCLUSIONS
These results indicate that mixed Th1 (TNF-α, IFN-γ , and IL-2) and Th2 (IL-10) immunity might play a role in the antitumor effect in terms of lymph node metastasis.

Keyword

Thyroid cancer, papillary; Cytokines; Cyclin-dependent kinase inhibitor p27; T-lymphocytes, helper-inducer; Neoplasm metastasis; Lymphocytic thyroiditis

MeSH Terms

Biomarkers
Cyclin-Dependent Kinase Inhibitor p27
Cytokines
Follow-Up Studies
Interferons
Interleukin-4
Interleukins
Lymph Nodes
Necrosis
Neoplasm Metastasis
RNA, Messenger
T-Lymphocytes, Helper-Inducer
Thyroid Gland
Thyroid Neoplasms
Thyroiditis
Thyroiditis, Autoimmune*
Biomarkers
Cyclin-Dependent Kinase Inhibitor p27
Cytokines
Interferons
Interleukin-4
Interleukins
RNA, Messenger

Figure

  • Fig. 1. p27 immunoreactivity (nuclear staining) on papillary thyroid carcinoma cells. Two-tiered grading system reveals a low grade (A, negative staining or faint staining less than 30% of tumor cells) and a high grade (B, positive staining more than 30% of tumor cells).


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