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Annexin A1: A new immunohistological marker of cholangiocarcinoma
Nuttanan Hongsrichan, Rucksak Rucksaken, Yaovalux Chamgramol, Porntip Pinlaor, Anchalee Techasen, Puangrat Yongvanit, Narong Khuntikeo, Chawalit Pairojkul, Somchai Pinlaor
Nuttanan Hongsrichan, Rucksak Rucksaken, Somchai Pinlaor, Department of Parasitology, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Yaovalux Chamgramol, Chawalit Pairojkul, Department of Pathology, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Porntip Pinlaor, Centre for Research and Development in Medical Diagnostic Laboratory, Faculty of Associated Medical Sciences, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Anchalee Techasen, Puangrat Yongvanit, Department of Biochemistry, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Narong Khuntikeo, Department of Surgery, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Author contributions: Hongsrichan N performed experiments, analyzed the data and wrote the manuscript; Rucksaken R analyzed the data; Chamgramol Y and Pairojkul C constructed tissue arrays and advised for immunohistochemical data; Pinlaor P revised the manuscript; Techasen A and Yongvanit P advised on siRNA experiment; Khuntikeo N provided specimens and advised clinical data; Pinlaor S designed the experiments and wrote the manuscript.
Supported by The Commission on Higher Education, Thailand (Strategic Scholarships for Frontier Research Network for the PhD Program Thai Doctoral degree); Khon Kaen University Research Foundation, Invitation Research from Faculty of Medicine, No. I55113; The Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, through the Health Cluster (SHeP-GMS), Thailand
Correspondence to: Somchai Pinlaor, PhD, Associate Professor, Department of Parasitology, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. psomec@kku.ac.th
Telephone: +66-43-348387 Fax: +66-43-202475
Received: October 27, 2012
Revised: December 28, 2012
Accepted: January 23, 2013
Published online: April 28, 2013
AIM: To evaluate a new immunohistological marker, annexin A1 (ANXA1), in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC).
METHODS: Expression of ANXA1 protein was investigated in liver tissues from patients with CCA and HCC by immunohistochemistry. Its expression on differences stages of tumor development was investigated in hamster CCA tissues induced by Opisthorchis viverrini and N-nitrosodimethylamine. Moreover, mRNA expression of ANXA1 was assessed in CCA cell lines by quantitative real-time polymerase chain reaction and silencing of ANXA1 gene expression using small interfering RNA.
RESULTS: In human CCA tissue arrays, immunohistochemical analysis revealed that the positive expression of ANXA1 was 94.1% (64/68 cases) consisting of a high expression (66.2%, 45/68 cases) and a low expression (33.8%, 23/68 cases). However, expression of ANXA1 protein was negative in all histologic patterns for HCC (46/46 cases) and healthy individuals (6/6 cases). In hamster with opisthorchiasis-associated CCA, the expression of ANXA1 was observed in the cytoplasm of inflammatory cells, bile duct epithelia and tumor cells. Grading scores of ANXA1 expression were significantly increased with tumor progression. In addition, mRNA expression of ANXA1 significantly increased in all of the various CCA cell lines tested compared to an immortalized human cholangiocyte cell line (MMNK1). Suppressing the ANXA1 gene significantly reduced the matrix metalloproteinase (MMP) 2 and MMP9, and transforming growth factor-β genes, but increased nuclear factor-κB gene expression.
CONCLUSION: ANXA1 is highly expressed in CCA, but low in HCC, suggesting it may serve as a new immunohistochemical marker of CCA. ANXA1 may play a role in opisthorchiasis-associated cholangiocarcinogenesis.
