Matrix Metalloproteinases 2 and 9 and Their Tissue Inhibitors in the Diagnostics of Medullary Thyroid Carcinoma

Appl Immunohistochem Mol Morphol. 2023 Feb 1;31(2):121-127. doi: 10.1097/PAI.0000000000001092. Epub 2022 Nov 28.

Abstract

Medullary Thyroid Carcinoma (MTC) is a tumor of the neuroendocrine system. In recent years, the need to assess the MTC diagnostic-related parameters has emerged with the aim to elucidate the mechanisms involved in this pathology. The objective of this study was to evaluate the role of Matrix Metalloproteinases (MMPs) 2 and 9, their tissue inhibitors of matrix metalloproteinases (TIMPs), S100 protein, and amyloid in the diagnostic of MTC. Thirty-two samples with MTC (72% women) were included in this cross-sectional study and divided by groups: T category 1 (T1)≤20 mm and T category 2 (T2) 20 to 40 mm of tumor size. MMPs 2 and 9, TIMPs 2 and 1, S100 protein, and calcitonin in tissues were obtained by immunohistochemical techniques. The presence of amyloid in tissue sections was detected on Thioflavin T-stained slides under fluorescent microscope. Percentage of positive cells (P) observed for MMP-2 was higher in those samples presenting T2 MTC with respect to those with T1 MTC ( P <0.05). Moreover, P-MMP-2 showed a direct correlation with higher T category of MTC (Rho=0.439, P < 0.001), whereas P-MPP-9 was directly correlated with S100 protein and the intensity of calcitonin in tissues (Rho=0.419, P =0.017; Rho=0.422, P =0.016, respectively. Therefore, MMPs were directly correlated with some traditional biomarkers of MTC. In this regard, P-MMP-2 was more expressed in type 2 MTC. Combining the analysis of traditional and other useful biomarkers of MTC as MMPs 2 and 9 could be a useful strategy in the diagnostic of MTC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / metabolism
  • Biomarkers, Tumor / analysis
  • Calcitonin
  • Carcinoma, Neuroendocrine* / diagnosis
  • Carcinoma, Neuroendocrine* / metabolism
  • Carcinoma, Neuroendocrine* / pathology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 2* / metabolism
  • Matrix Metalloproteinase 9* / metabolism
  • S100 Proteins
  • Thyroid Neoplasms* / diagnosis
  • Thyroid Neoplasms* / metabolism
  • Thyroid Neoplasms* / pathology
  • Tissue Inhibitor of Metalloproteinases* / metabolism

Substances

  • Amyloid
  • Biomarkers, Tumor
  • Calcitonin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • S100 Proteins
  • Tissue Inhibitor of Metalloproteinases

Supplementary concepts

  • Thyroid cancer, medullary