Histochemistry and Cell Biology

, Volume 149, Issue 6, pp 635–644 | Cite as

Expression of serine peptidase inhibitor Kunitz type 1 in differentiated thyroid cancer

  • Chien-Liang Liu
  • Po-Sheng Yang
  • Ming-Nan Chien
  • Yuan-Ching Chang
  • Chi-Hsin Lin
  • Shih-Ping ChengEmail author
Original Paper


SPINT1, also known as HAI-1, is a Kunitz-type serine protease inhibitor that inhibits multiple proteases including hepatocyte growth factor (HGF) activator and matriptase. SPINT1 has been shown to modulate HGF/MET activation in certain cancer types. In the present study, we analyzed microarray datasets and found that SPINT1 was consistently upregulated in differentiated thyroid cancer. SPINT1 protein expression was investigated using tissue microarrays and independent samples of our 143 patients. Strong SPINT1 expression was observed in 61–68% of papillary thyroid cancer and 41–50% of follicular thyroid cancer. The overexpression diminished in anaplastic thyroid cancer. The SPINT1 expression in normal thyroid tissues and benign thyroid lesions was low. Furthermore, we noted that the SPINT1 expression was associated with extrathyroidal invasion, lymphovascular invasion, lymph node metastasis, advanced TNM stage, and a higher risk of recurrence in differentiated thyroid cancer. The results were in accordance with our analysis of The Cancer Genome Atlas data. In conclusion, an overexpression of SPINT1 appears to be associated with an invasive phenotype in differentiated thyroid cancer.


Serine protease inhibitor Hepatocyte growth factor Thyroid cancer Invasion 



This work was supported by research grants from the Ministry of Science and Technology of Taiwan (MOST-104-2314-B-195-004-MY3) and MacKay Memorial Hospital (MMH-10712 and MMH-E-107-10).

Compliance with ethical standards

Informed consent

Institutional review board approval was obtained for the study, and the need for informed consent was waived.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

418_2018_1660_MOESM1_ESM.tif (9.3 mb)
Supplementary material 1 Supplemental Figure 1. (a) Representative image of a tissue microarray slide containing cores from malignant thyroid tumors and corresponding normal thyroid tissues. Red boxes indicate sets of three cores from the same primary tumor. (b) Representative microphotographs from two cases, demonstrating similar expression levels of SPINT1 in different regions of the same tumor. Scale bar, 500 μm (TIF 9536 KB)
418_2018_1660_MOESM2_ESM.tif (230 kb)
Supplementary material 2 Supplemental Figure 2. Scatter plots of H-score of SPINT1 immunohistochemical staining versus clinicopathological factors in differentiated thyroid cancer (n = 143). ATA, American Thyroid Association. MACIS, metastases, age, completeness of resection, invasion, and size (papillary thyroid cancer only). ***, P < 0.001 (TIF 229 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of SurgeryMacKay Memorial Hospital and Mackay Medical CollegeTaipeiTaiwan
  2. 2.Department of Medical ResearchMacKay Memorial HospitalTaipeiTaiwan
  3. 3.Division of Endocrinology and Metabolism, Department of Internal MedicineMacKay Memorial Hospital and Mackay Medical CollegeTaipeiTaiwan
  4. 4.Department of Bioscience TechnologyChung Yuan Christian UniversityTaoyuanTaiwan
  5. 5.Department of Pharmacology, Graduate Institute of Medical SciencesTaipei Medical UniversityTaipeiTaiwan

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