Lipocalin-2 (LCN-2) and Twist can help differentiate between benign and malignant thyroid nodules, according to a new study published in Annals of Diagnostic Pathology. They may also be valuable predictive biomarkers in thyroid cancer patients.

High LCN-2 expression has been reported in many tumors. Similarly, research has shown that Twist is overexpressed in different tumors and induces epithelial-to-mesenchymal transition, which is crucial for metastasis, tumorigenesis, and cancer progression. These findings suggest they could be biomarkers as well as therapeutic targets in cancer.

In the present study, a team of researchers led by Sema Hücümenoğlu, MD, from the Department of Pathology at Ankara Training and Research Hospital in Turkey examined LCN-2 and Twist expression in thyroid cancers and elucidated their role in epithelial-to-mesenchymal transition. 

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The researchers analyzed a total of 249 patients. Of these, 120 had papillary thyroid carcinoma, 34 had follicular thyroid carcinoma, 15 had medullary thyroid carcinoma, 20 had noninvasive follicular thyroid neoplasm with papillary-like nuclear features, 47 had follicular adenoma, and 13 had nodular hyperplasia.

Read more about the treatment of medullary thyroid carcinoma.

The results showed there was a significant increase in the expression of LCN-2 and Twist in nodular hyperplasia and follicular adenomas, compared to the other types of thyroid cancer. The researchers also found that the expression of Twist was high in cases with a positive epithelial-to-mesenchymal transition phenotype.

LCN-2 is a circulatory protein that plays a role in the transportation of small and hydrophobic molecules such as steroids, free fatty acids, prostaglandins, and hormones to target organs. Twist is a transcription factor with the helix-loop-helix domain, which is involved in embryonic development. 


Celepli P, Bigat İ, Karabulut S, Celepli S, Hücümenoğlu S. Evaluation of Lipocalin-2 and Twist expression in thyroid cancers and its relationship with epithelial mesenchymal transition. Ann Diagn Pathol. Published online May 12, 2022. doi:10.1016/j.anndiagpath.2022.151973