High-mobility group AT-hook 2: an independent marker of poor prognosis in intrahepatic cholangiocarcinoma.

High-mobility group AT-hook 2 (HMGA2) regulates cell growth, differentiation, apoptosis, and neoplastic transformation. Previous studies have shown that malignant tumors expressing HMGA2, such as gastric, lung, and colorectal carcinomas, usually have a poor prognosis. HMGA2 expression and its clinical significance in intrahepatic cholangiocarcinomas have not been studied. We identified 55 intrahepatic cholangiocarcinomas resected at our institution from 1994 to 2003. Hematoxylin-eosin-stained slides were reviewed, and histopathologic characteristics were recorded, including mitotic count, tumor grade, vascular and perineural invasion, lymph node metastasis, and margin status. Using immunohistochemical stains, we examined expression of HMGA2, p53, p16, Kit, α-fetoprotein, and Ki-67, and we analyzed the correlation of survival with clinicopathological characteristics and immunohistochemical findings. Positive staining for HMGA2, p53, p16, Kit, α-fetoprotein, and Ki-67 was seen in 18 (33%), 37 (69%), 26 (47%), 21 (38%), 2 (4%), and 34 (63%) tumors, respectively. HMGA2 expression correlated positively with p53 expression (P = .02; ρ = 0.32) and negatively with p16 expression (P = .04; ρ = -0.28). Univariate analysis showed that HMGA2 expression and lymph node metastasis were associated with shorter patient survival and were independent indicators of poor survival (P = .02 and P = .03, respectively). Tumorigenic effects of HMGA2 in intrahepatic cholangiocarcinoma may partly reflect its ability to negatively regulate expression of p16 tumor suppressors and to be associated with p53 abnormalities.