Abstract
Background/purpose
Local ablation therapy (LAT) is a widely used treatment for hepatocellular carcinoma (HCC) because it is less invasive than hepatic resection. The precise molecular mechanism underlying local HCC recurrence after LAT is largely unknown. The CD44 standard isoform (CD44s) is involved in epithelial–mesenchymal transition (EMT) in HCC. We investigate the significance of CD44s expression and EMT expression profile in local HCC recurrence after LAT.
Methods
We studied the expression levels of CD44s, EMT expression profile (E-cadherinlow/vimentinhigh expression) and their association with clinicopathological factors in 30 HCC samples from patients with locally recurrent HCCs after LAT following hepatic resection. The alterations of CD44s expression was compared with those in initial HCCs from 150 patients without prior any anticancer treatment including LAT.
Results
A high CD44s expression was significantly associated with the EMT expression profile (P = 0.002), and it was also detected with a higher frequency in the locally recurrent HCCs after LAT compared to initial HCCs (P < 0.001). In addition, high CD44s expression was associated with the intrahepatic dissemination of HCC after LAT (P = 0.006).
Conclusions
These results suggest that high CD44s expression is associated with the aggressive recurrence pattern via EMT after LAT for HCC.
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References
El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–27.
Poon RT, Ng IO, Fan ST, Lai EC, Lo CM, Liu CL, et al. Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort. J Clin Oncol. 2001;19:3037–44.
Poon RT, Fan ST, Tsang FH, Wong J. Locoregional therapies for hepatocellular carcinoma: a critical review from the surgeon’s perspective. Ann Surg. 2002;235:466–86.
Tiong L, Maddern GJ. Systematic review and meta-analysis of survival and disease recurrence after radiofrequency ablation for hepatocellular carcinoma. Br J Surg. 2011;98:1210–24.
Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial–mesenchymal transitions in development and disease. Cell. 2009;139:871–90.
Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero CP, Sterner CJ, et al. The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell. 2005;8:197–209.
Shioiri M, Shida T, Koda K, Oda K, Seike K, Nishimura M, et al. Slug expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Br J Cancer. 2006;94:1816–22.
Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 2003;4:33–45.
Zoller M. CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 2011;11:254–67.
Mima K, Okabe H, Ishimoto T, Hayashi H, Nakagawa S, Kuroki H, et al. CD44s regulates the TGF-beta-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer Res. 2012;72:3414–23.
Dodd GD 3rd, Frank MS, Aribandi M, Chopra S, Chintapalli KN. Radiofrequency thermal ablation: computer analysis of the size of the thermal injury created by overlapping ablations. AJR Am J Roentgenol. 2001;177:777–82.
Masuda T, Beppu T, Ishiko T, Horino K, Baba Y, Mizumoto T, et al. Intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy. J Hepatobiliary Pancreat Surg. 2008;15:589–95.
The Liver Cancer Study Group of Japan. The General Rules for the Clinical and Pathological Study of Primary Liver Cancer. The 5th Edition, Revised Version ed. Tokyo: Kanehara; 2009.
Minagawa M, Ikai I, Matsuyama Y, Yamaoka Y, Makuuchi M. Staging of hepatocellular carcinoma: assessment of the Japanese TNM and AJCC/UICC TNM systems in a cohort of 13,772 patients in Japan. Ann Surg. 2007;245:909–22.
Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol. 2002;20:1527–36.
Llovet JM, Vilana R, Bru C, Bianchi L, Salmeron JM, Boix L, et al. Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma. Hepatology. 2001;33:1124–9.
Poon RT, Lau C, Pang R, Ng KK, Yuen J, Fan ST. High serum vascular endothelial growth factor levels predict poor prognosis after radiofrequency ablation of hepatocellular carcinoma: importance of tumor biomarker in ablative therapies. Ann Surg Oncol. 2007;14:1835–45.
Tsuchiya K, Komuta M, Yasui Y, Tamaki N, Hosokawa T, Ueda K, et al. Expression of keratin 19 is related to high recurrence of hepatocellular carcinoma after radiofrequency ablation. Oncology. 2011;80:278–88.
Xia F, Lai EC, Lau WY, Ma K, Li X, Bie P, et al. High serum hyaluronic acid and HBV viral load are main prognostic factors of local recurrence after complete radiofrequency ablation of hepatitis B-related small hepatocellular carcinoma. Ann Surg Oncol. 2012;19:1284–91.
Ahmad F, Gravante G, Bhardwaj N, Strickland A, Basit R, West K, et al. Changes in interleukin-1beta and 6 after hepatic microwave tissue ablation compared with radiofrequency, cryotherapy and surgical resections. Am J Surg. 2010;200:500–6.
Acknowledgments
We thank Keisuke Miyake and Naoko Yokoyama for their valuable technical assistance.
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The authors declare that they have no conflict of interest.
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Mima, K., Hayashi, H., Imai, K. et al. High CD44s expression is associated with the EMT expression profile and intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy. J Hepatobiliary Pancreat Sci 20, 429–434 (2013). https://doi.org/10.1007/s00534-012-0580-0
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DOI: https://doi.org/10.1007/s00534-012-0580-0