Expression of integrin α_vβ₃ in medullary thyroid carcinoma

Abstract

Aim: Tumor markers often remain elevated after intended curative resection of medullary thyroid carcinoma (MTC). The aim of this study was to determine the expression of α_vβ₃, a promising theranostics target, in MTC and its metastases. Materials & methods: A_vβ₃ expression was analyzed in 104 patients using a tissue microarray and correlated with clinicopathological variables and survival. Results: Cytoplasmic α_vβ₃ positivity was seen in 70 patients and was associated with lymph node metastases at time of initial surgery. Membranous positivity was considered positive in 30 patients and was associated with sporadic MTC. Conclusion: A_vβ₃ was expressed in the cytoplasm of 67% of MTC patients. Membranous expression, which is presumably most relevant for the theranostic use of α_vβ₃, was seen in 29%.

Article highlights

• After intended curative resection of medullary thyroid carcinoma (MTC), calcitonin levels often remain elevated indicating remnant disease or metastasis.

• There is a demand for new imaging and therapeutic options for patients with MTC.

• A_vβ₃, an integrin expressed in many tumors, is a promising target for nuclear imaging and treatment using radiolabeled arginine-glycine-aspartic acid (RGD).

• Cytoplasmic and membranous α_vβ₃ expression was analyzed using a tissue microarray including primary tumors and lymph node metastases of 104 and 27 patients, respectively.

• Cytoplasmic expression was considered positive in 67% of patients and was associated with lymph node metastases at the time of initial surgery.

• Membranous expression, which is thought to be most relevant for the theranostic use of α_vβ, was seen in 29% of patients and was associated with sporadic MTC.

• Survival analysis showed no prognostic value of α_vβ₃.

• The correlation of immunohistochemical α_vβ₃ expression and uptake of radiolabeled RGD should be further assessed in patients with membranous α_vβ₃ expression.

Keywords: :

• medullary thyroid carcinoma
• nuclear imaging
• nuclear therapy
• tissue microarray
• α_vβ₃

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/14796694.2024.2376511

Acknowledgments

We would like to thank H Morreau for his time to select the MTC tissue of the LUMC, D Castiliego for his contribution in the construction of the TMA, D Lobeek for sharing her knowledge about α_vβ₃ staining and the α_vβ₃ staining protocol used in the RUMC, and U Flucke for her contribution to the establishment and assessment of the α_vβ₃ stained TMA.

Author contributions

All authors contributed to the article and approved the submitted version.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All procedures performed in this study were in accordance with ethical standards of the Institutional Review Board of the UMC Utrecht and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.