Expression of High Mobility Group AT-Hook 2 (HMGA2) in Intrahepatic Cholangiocarcinomas: An Independent Prognostic Marker Associated with Poor Prognosis
Chung-Ta Lee, Tsung-Teh Wu, Christine Lohse, Lizhi Zhang. National Cheng Kung University Hospital, Tainan, Taiwan; Mayo Clinic, Rochester, MN
Background: High mobility group AT-hook 2 (HMGA2) is an important regulator for cell growth, differentiation, apoptosis, and neoplastic transformation. Previous studies have shown that malignant tumors expressing HMGA2 such as gastric, lung, and colorectal carcinomas usually had poor prognosis. HMGA2 expression and its clinical significance in intrahepatic cholangiocarcinomas have not been studied before.
Design: We identified 55 intrahepatic cholangiocarcinomas resected at our institute from 1994 to 2003. H&E slides from all cases were reviewed and the histopathological features of tumor size, mitotic count, tumor grade, presence of satellite nodules, desmoplasia, tumor necrosis, vascular and perineuronal invasion, lymph node metastasis, and margin status were recorded. By using immunohistochemical staining, we examined expression of HMGA2, P16, P53, Kit, AFP, and Ki-67 index. Associations of clinicopathologic features and immunohistochemical findings with patient survival were evaluated using Cox proportional hazards regression.
Results: The mean age of 55 patients (21 male; 34 female) was 60.9 years old. Twelve (23%) cases had positive lymph node metastasis. Expression of HMGA2, P16, P53, Kit, and AFP was observed in 18 (32%), 26 (47%), 37 (69%), 21 (38%), and 2 (4%) of the intrahepatic cholangiocarcinomas, respectively. The mean Ki-67 index was 9.1% (ranging from 0 – 90%). Univariate analysis showed that HMGA2 expression and lymph node metastasis were associated with shorter patient survival (p = 0.02 and 0.03, respectively). Higher Ki-67 index was associated poor survival although it did not reach statistical significance (p=0.09). The other histopathological features and the expression status of P16, P53, Kit, and AFP did not show associations with patient survival. Multivariable analysis showed that HMGA-2 expression (hazard ratio 2.10; p=0.03) and lymph node metastasis (hazard ratio 2.25; p=0.04) were independent prognostic factors associated with poor survival.
Conclusions: HMGA2 is expressed in a subset (32%) of intrahepatic cholangiocarcinomas and is an independent prognostic marker associated with poor survival.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 204, Tuesday Morning