The role of transglutaminase 2 expression in determining metastasis risk, recurrence, and survival in differentiated papillary thyroid cancers

The Role of Transglutaminase 2 Expression in Determining Metastasis Risk, Recurrence, and Survival in Differentiated Papillary Thyroid Cancers Objectives: Transglutaminase 2 (TG2), also known as tissue transglutaminase, is a member of transglutaminase enzyme family. Transglutaminase 2 is associated with mobilization, invasion and chemoresistance of tumor cells. Aberrant regulation of genes encoding TG2, has been recognized in many different types of cancers. Different studies have shown that TG2 expression is higher in metastatic tissues and chemoresistant tumors than the primary tumor. In our study, we aimed to investigate the role of TG2 expression in tumor biology, metastasis risk, recurrence and survival. Patients and Methods: Our study included 76 PTC patients (n=76); thirty of them had no evidence of metastasis, 30 had only lymph node metastasis and 16 patients had distant metastasis. The expression of TG2 antibody was evaluated by immunohistochemical methods in the primary tumor and metastatic tissues. Ekstra-tumoral thyroid tissue was used as control. Results: Seventy-six patients, 55 (72%) of whom were female, with a median disease duration of 107 (60-216) months and a median age of 52 (24-81) were included in the study. 30 of them (39,5%) had no metastasis, 30 of them (39,5%) had only lymph node metastasis and 16 patients (21,1 %) have distant metastasis. In the follow-up, mortality was observed in 1 (1,3 %), recurrence in 9 (11,8 %), progression in 4 (5,3 %), stable disease in 12 (15,8 %), and complete remission in 50 (65,8 %) patients. The cases were divided into two groups as low risk and high risk according to the primary tumor TG2 staining score. Among the groups; there was a significant difference between vascular invasion (p=0,001), thyroid capsule invasion (p<0,001), extrathyroidal soft tissue invasion (p<0,001), intrathyroidal invasion (p<0,001), lymph node metastasis (p<0,001) and complete remission(p=0,036). It was shown that the risk of lymph node metastasis increased by 4,26 times with 1 point increase in the primary tumor's TG2 staining score. However, no significant difference was found in distant metastasis (p>0,05). Conclusions: TG2 staining score can be an important predictor for lymph node metastasis and recurrence. High levels of TG2 staining score should be determined at the time of diagnosis. More aggressive treatments and close follow-up should be performed in patients with a high TG2 score. (This study was funded by Istanbul University with the project number TTU-2018-28047.