Study of tumor transglutaminase 2 expression in gallbladder cancer – Is it a novel predictor of survival?

BACKGROUNDS/AIMS: Transglutaminase 2 (TG2) is known to be an important mediator of inflammation induced carcinogenesis pathway. Chronic inflammation is the most important causative factor in Gallbladder cancer (GBC) carcinogenesis. We analyzed the expression of TG2 in GBC and its role as potential prognostic marker, first of its kind study. METHODS: We analyzed TG2 expression in 100 cases of GBC and 28 cases of non-cancer gallbladder specimen (calculus cholecystitis). We studied TG2 expression in GBC in comparison to control group and evaluated its role as a potential prognostic marker. RESULTS: TG2 score (1-9) was calculated by multiplying percentage cytoplasmic expression (P) with intensity of expression (I) in tumor cells. Positive TG-2 expression was observed in 62% of GBC patients compared to only 21% (n=6) in control group (p=0.001). In curative resection subgroup (n=54), TG2 positive patients showed shorter disease free survival rate (p=0.04) and higher rate of recurrence (p=0.03) compared to TG2 negative patients. TG2 positive expression was observed in 15/16 of patients with recurrent disease. In palliative treatment subgroup, patients with strong TG2 positive expression had poorer disease specific survival (p=0.01) as compared to weakly positive group. On multivariate analysis, lymph node status (p=0.03) and TG2 expression (p=0.037), were found to be significant predictor of recurrence and eventual survival. CONCLUSIONS: Positive TG2 expression was related to higher recurrence rates post curative surgery, shorter disease free and overall survival and ultimately portended poor prognosis. It may be helpful in better prognostication and tailoring therapeutic approach for better management of GBC.