Document Type : Short Communication


1 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran


Background & Objective: Differential diagnosis between cholangiocarcinoma (CCA) and metastatic pancreatic ductal adenocarcinoma (PDA) in the liver is difficult and so far, no specific immunohistochemical marker is reported to differentiate these two tumors. Considering the existing literature, the level of expression of Annexins (Annexin A1, 10 and 13) have been studied for differential diagnosis between these two tumors by molecular methods and promising results have been reported. Therefore, in this study, we tried to investigate the immunohistochemical value of these three Annexins for the differential diagnosis of CCA and PDA in the liver.
Methods: The articles that reported the research subject in 10 years (2009-2019), including 45 cases of CCA and 50 cases of metastatic PDA in the liver were evaluated considering the presence or absence of AnnexinA1 (ANXA1), Annexin A10 (ANXA10) and Annexin A13 (ANXA13) expression by immunohistochemistry, were investigated.
Results & Conclusion: This study showed, ANXA1 was positive both in PDA and CCA, ANXA10 was positive in ~60% of PDA cases and ~40% of CCA cases, and ANXA13 was mostly negative in both groups. The best sensitivity was found in cytoplasmic and nuclear ANXA1 (80% and 84%, respectively) to distinguish PDA from CCA and vice versa. The best specificity was observed in ANXA10 and ANXA13 to distinguish PDA from CCA. Also, ANXA13 had the best specificity to distinguish CCA from PDA. Our investigations showed that, ANXA1 probably can classify positive cases correctly, but it cannot discriminate PDA from CCA. ANXA10 had fair sensitivity and specificity to discriminate PDA from CCA. ANXA13 apparently had a high specificity that can help to narrow-down the differential diagnoses. 


Main Subjects

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  1. Kälsch J., et al. Annexin A10 optimally differentiates between intrahepatic cholangiocarcinoma and hepatic metastases of pancreatic ductal adenocarcinoma: a comparative study of immunohistochemical markers and panels, Virchows Arch. 2017 ;470(5):537-543. [DOI:10.1007/s00428-017-2114-2]
  2. Hongsrichan N, Rucksaken R, Chamgramol Y, Pinlaor P, Techasen A, Yongvanit P, Khuntikeo N, Pairojkul C, Pinlaor S, Annexin A1: A new immunohistological marker of cholangiocarcinoma, World J Gastroenterol. 2013 ;19(16):2456-65. [DOI:10.3748/wjg.v19.i16.2456]
  3. Padden J, Ahrens M, Kalsch J, Bertram S, Megger DA, Bracht T, et al. Immunohistochemical markers distinguishing Cholangiocellular carcinoma (CCC) from pancreatic ductal adenocarcinoma (PDAC) discovered by proteomic analysis of microdissected cells. Mol Cell Proteomics. 2016;15:1072-1082. [DOI:10.1074/mcp.M115.054585]
  4. Kang JS, Calvo BF, Maygarden SJ, Caskey LS, Mohler JL, Ornstein DK. Dysregulation of annexin I protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer. Clin Cancer Res. 2002;8(1):117-23.
  5. Fernandez Moro C, Fernandez-Woodbridge A, Alistair D'souza M, Zhang Q, Bozoky B, Kandaswamy SV, et al. Immunohistochemical typing of adenocarcinomas of the pancreatobiliary system improves diagnosis and prognostic stratification. PLoS ONE. 2016;11(11): [DOI:10.1371/journal.pone.0166067]
  6. Liu QH, Shi ML, Bai J, Zheng JN., Identification of ANXA1 as a lymphatic metastasis and poor prognostic factor in pancreatic ductal adenocarcinoma, Asian Pac J Cancer Prev. 2015;16(7):2719-24. [DOI:10.7314/APJCP.2015.16.7.2719]
  7. Gao Y, Chen Y, Xu D, Wang J, Yu G. Differential expression of ANXA1 in benign human gastrointestinal tissues and cancers. BMC Cancer. 2014;14:520 . [DOI:10.1186/1471-2407-14-520]
  8. Wang D, Zhang H, Fang Z, Yu G., Annexin-1 downregulation is associated with clinical outcome in Chinese patients with hilar cholangiocarcinoma, Eur Surg Res. 2010;45(3-4):151-7. [DOI:10.1159/000320237]
  9. Bai XF, Ni XG, Zhao P, Liu SM, Wang HX, Guo B, et al. Overexpression of annexin 1 in pancreatic cancer and its clinical significance. World J Gastroenterol. 2004;10(10):1466-70. [DOI:10.3748/wjg.v10.i10.1466]
  10. Iglesias JM, Morgan RO, Jenkins NA, Copeland NG, Gilbert DJ, Fernandez MP., Comparative genetics and evolution of annexin A13 as the founder gene of vertebrate annexins, Mol Biol Evol. 2002 May;19(5):608-18 [DOI:10.1093/oxfordjournals.molbev.a004120]