Hepatoblastoma survival and the prognostic role of cancer stem cell markers
Purpose: Hepatoblastoma (HB) is an embryonal tumor of the liver that occurs in infants and young children. Complete surgical resection and cisplatin-containing chemotherapy are crucial for cure in HB. Cancer stem cells (CSCs) constitute a newly identified subpopulation, which may differentiate into heterogeneous progenies of malignant cells. The aim of this study was to assess the survival outcome and the prognostic value of CSCs markers (CD133, CD90 and CD44) in a cohort of HB patients from Egypt.
Methods: Disease status of 43 HB patients was evaluated at the main checkpoints of therapy and during follow-up. Treatment included surgical tumor resection and systemic chemotherapy (cisplatin, 5-fluorouracil, doxorubicin, and vincristine). Protein and RNA expressions of CD44, CD 90 and CD 133 were assessed by immunohistochemistry and quantitative PCR.
Results: The OS for all patients was 58.2 at 4 years. Patients with localized disease stages (I&II) had a better OS than those with advanced stages (III&IV) (81.9% versus 30%, p<0.001). Total surgical resection was superior to incomplete/no resection (83.8% versus 25.2 %; p<0.001). The OS was significantly correlated with tumor response (p<0.001) and each of CD44, CD 90, CD 133 expression (p<0.001) whereas reduced DFS was associated with CD44 and CD133 expression (p<0.001).
Conclusion: Localized disease is associated with higher OS than more advanced stages III and IV. Complete surgical resection facilitated with systemic preoperative chemotherapy in initially irresectable cases can improve survival in HB while CSC markers (CD133, 44, and 90) can predict survival and response to treatment in HB patients.
Cite this article as:
Fawzy M, Bahnassy A, El-Wakil M, Abdel-Sayed A. Hepatoblastoma survival and the prognostic role of cancer stem cell markers. Int J Cancer Ther Oncol 2014; 2(1):02011.
Meyers RL. Tumors of the liver in children. Surg Oncol 2007; 16:195–203.
Emre S, Umman V, Rodriguez-Davalos M. Current concepts in pediatric liver tumors. Pediatr Transplant 2012; 16:549–563.
Litten JB, Tomlinson GE. Liver tumors in children. Oncologist 2008; 13: 812–820.
Perilongo G, Shafford E, Plaschkes J; Liver Tumour Study Group of the International Society of Paediatric Oncology. SIOPEL trials using preoperative chemotherapy in hepatoblastoma. Lancet Oncol 2000; 1:94-100.
Stiller CA, Pritchard J, Steliarova-Foucher E. Liver cancer in European children: incidence and survival, 1978-1997. Report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006; 42:2115-2123.
McLaughlin CC, Baptiste MS, Schymura MJ, Nasca PC, Zdeb MS. Maternal and infant birth characteristics and hepatoblastoma. Am J Epidemiol 2006; 163: 818-828.
Boman F, Bossard C, Fabre M, Diab N, Bonnevalle M, Boccon-Gibod L. Mesenchymal hamartomas of the liver may be associated with increased serum alpha foetoprotein concentrations and mimic hepatoblastomas. Eur J Pediatr Surg 2004; 14:63-66.
Ortega JA, Douglass EC, Feusner JH, Reynolds M, Quinn JJ, Finegold MJ, et al. Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: A report from the Children's Cancer Group and the Pediatric Oncology Group. J Clin Oncol 2000; 18:2665-2675.
Zimmermann A. The emerging family of hepatoblastoma tumours: from ontogenesis to oncogenesis. Eur J Cancer 2005; 41:1503-1514.
Purcell R, Childs M, Maibach R, Miles C, Turner C, Zimmermann A, Sullivan M. HGF/c-Met related activation of β-catenin in hepatoblastoma. J Exp Clin Cancer Res 2011; 30:96.
Dalerba P, Cho RW, Clarke MF. Cancer stem cells: models and concepts. Annu Rev Med 2007; 58:267-284.
Park CY, Tseng D, Weissman IL. Cancer stem cell-directed therapies: recent data from the laboratory and clinic. Mol Ther 2009; 17:219-230.
Hayashi S, Fujita K, Matsumoto S, Akita M, Satomi A. Isolation and identification of cancer stem cells from a side population of a human hepatoblastoma cell line, HuH-6 clone-5. Pediatr Surg Int 2011; 27:9–16.
Lingala S, Cui YY, Chen X, Ruebner BH, Qian XF, Zern MA, Wu J. Immunohistochemical staining of cancer stem cell markers in hepatocellular carcinoma. Exp Mol Pathol 2010; 89:27-35.
Klonisch T, Wiechec E, Hombach-Klonisch S, Ande SR, Wesselborg S, Schulze-Osthoff K, Los M. Cancer stem cell markers in common cancers– therapeutic implications. Trends Mol Med 2008; 14:450-460.
McCarville MB, Roebuck DJ. Diagnosis and staging of hepatoblastoma: imaging aspects. Pediatr Blood Cancer 2012; 59:793-799.
King SJ, Babyn PS, Greenberg ML, Phillips MJ, Filler RM. Value of CT in determining the resectability of hepatoblastoma before and after chemotherapy. AJR Am J Roentgenol 1993; 160:793-8.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors (RECIST guidelines). J Natl Cancer Inst 2000; 92:205-216.
National Cancer Institute at the National Institutes of Health. Childhood Liver Cancer Treatment. Treatment of Hepatoblastoma. Available from http://www.cancer.gov/cancertopics/pdq/treatment/childliver/HealthProfessional/page5. (Accessed on March 29, 2013)
Khoo TK, Coenen MJ, Schiefer AR, Kumar S, Bahn RS. Evidence for Enhanced Thy-1 (CD90) Expression in Orbital Fibroblasts of Patients with Graves’ Ophthalmopathy. Thyroid 2008; 18:1291-1296.
Olempska M, Eisenach PA, Ammerpohl O, Ungefroren H, F, Kalthoff H. Detection of tumor stem cell markers in pancreatic carcinoma cell lines. Hepatobiliary Pancreat Dis Int 2007; 6:92-97.
Spector LG, Birch J. The Epidemiology of Hepatoblastoma. Pediatr Blood Cancer 2012; 59:776-779.
Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, et al. SEER cancer statistics review, (Vintage 2009 Populations), National Cancer Institute. Bethesda, MD 2011; 1975–2008.
Zsíros J, Maibach R, Shafford E, Brugieres L, Brock P, Czauderna P, et al. Successful treatment of childhood high-risk hepatoblatoma with dose-intensive multiagent chemotherapy and surgery: final results of the SIOPEL-3HR study. J Clin Oncol 2010; 28:2584–2590.
Tiao GM, Bobey N, Allen S, Nieves N, Alonso M, Bucuvalas J, et al. The current management of hepatoblastoma. A combination of chemotherapy, conventional resection, and liver transplantation. J Pediatr 2005; 146:204–211.
Pritchard J, Brown J, Shafford E, Perilongo G, Brock P, Dicks-Mireaux C, et al. Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: A successful approach-results of the first prospective study of the International Society of Pediatric Oncology. J Clin Oncol 2000; 18:3819–3828.
Garvalov BK, Acker T. Cancer stem cells: A new framework for the design of tumor therapies. J Mol Med 2011; 89:95-107.
Saini V, Shoemaker RH. Potential for therapeutic targeting of tumor stem cells. Cancer Sci 2010; 101:16–21.
Murase M, Kano M, Tsukahara T, Takahashi A, Torigoe T, Kawaguchi S, et al. Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas. Br J Cancer 2009; 101:1425–1432.
Frank NY, Schatton T, Frank MH. The therapeutic promise of the cancer stem cell concept. J Clin Invest 2010; 120:41–50.
This work is licensed under a Creative Commons Attribution 3.0 License.
International Journal of Cancer Therapy and Oncology (ISSN 2330-4049)
© International Journal of Cancer Therapy and Oncology (IJCTO)
To make sure that you can receive messages from us, please add the 'ijcto.org' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.