Transglutaminase 2 expression is associated with increased risk of lymph node metastasis and recurrence in papillary thyroid cancer

Transglutaminase 2 (TG2) is associated with mobilization, invasion, and chemoresistance of tumor cells. We aimed to determine whether the immunohistochemical staining with TG2 antibody differs between metastatic and non-metastatic papillary thyroid cancer patients. We included 76 patients with papillary thyroid cancer (72% female, median age 52 (24–81) years, follow-up time 107 (60–216) months). Thirty of them with no metastasis, 30 of them with only lymph node metastasis and 16 patients with distant ± lymph node metastasis. Immunohistochemical staining of TG2 antibody was evaluated in the primary tumor and extra-tumoral tissue. We also divided subjects into two groups according to their primary tumor TG2 staining score (group A, high risk group: ≥3, n = 43; group B, low risk group: <3, n = 33). Vascular invasion (p < 0.001), thyroid capsule invasion (p < 0.001), extrathyroidal extension (p < 0.001), intrathyroidal dissemination (p = 0.001), lymph node metastasis (p < 0.001), presence of aggressive histology (p < 0.001) were significantly higher in group A. No significant difference was found between the groups in terms of distant metastasis. Based on ATA risk classification 95.5% of patients with low risk were in group B but 86.8% of intermediate risk and 56.3% of high risk were in group A. In regression analysis, lymph node metastasis increased by 1.9 times with each one point increase in TG2 staining score. TG2 staining score of the primary tumor may be a predictive factor for lymph node metastasis. High or low TG2 scores may effect the frequency of follow-up and decision of treatment regimens.