Aim VEGF and AFP mRNA determinations in the blood are promising prognostic factors for patients with HCC. This study explores their potential prognostic synergy in a cohort of HCC patients evaluated for potentially curative therapies. Methods One hundred twenty-four patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (a) histological diagnosis of HCC and assessment of tumour grade and (b) determination of AFP mRNA status and VEGF levels in the blood before therapy. Results At baseline evaluation, 40% of the study group had AFP mRNA in the blood (AFP mRNA positive), and 35% had VEGF23 pg ml？1 (VEGF positive). Surgery was performed in 58 patients (47%), 54 (43%) had tumour ablation, and 12 had chemoembolisation (10%). Median follow-up and survival of the study group were 19 and 26 months (range, 1 to 60), respectively. The association of AFP mRNA and VEGF proved to be prognostically more accurate than their single use in discriminating the risk of death (ROC curve analysis) and survival probability (Cox analysis). In particular, we identified 3 main molecular stages (0,0001): both negative (3-year survival = 63%), one positive (3-year survival = 40%), both positive (3-year survival = 16%). Multivariate analysis identified BCLC staging, surgery, and molecular staging as the most significant survival variables. Conclusions The preoperative determination of AFP mRNA status and VEGF may potentially refine the prognostic evaluation of HCC patients and improve the selection process for potentially curative therapies.
References
[1]
Pang R, Poon RTP (2006) Angiogenesis and antiangiogenic therapy in hepatocellular carcinoma. Cancer Lett 242: 151–67.
[2]
Poon RT, Fan ST, Wong J (2001) Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 19: 1207–25.
[3]
Schwartz ME, D'Amico F, Vitale A, Emre S, Cillo U (2008) Liver transplantation for hepatocellular carcinoma: Are the milan criteria still valid? Eur J Surg Oncol 34: 256–62.
[4]
Schwarz RE, Smith DD (2008) Trends in local therapy for hepatocellular carcinoma and survival outcomes in the us population. Am J Surg 195: 829–36.
[5]
Pawlik TM, Gleisner AL, Anders RA, Assumpcao L, Maley W, et al. (2007) Preoperative assessment of hepatocellular carcinoma tumor grade using needle biopsy: implications for transplant eligibility. Ann Surg 245: 435–42.
[6]
Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42: 1208–36.
[7]
Llovet JM, Bruix J (2008) Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 48: Suppl 1S20–37.
[8]
Pang RWC, Joh JW, Johnson PJ, Monden M, Pawlik TM, et al. (2008) Biology of hepatocellular carcinoma. Ann Surg Oncol 15: 962–71.
[9]
Poon RTP, Ho JWY, Tong CSW, Lau C, Ng IOL, et al. (2004) Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma. Br J Surg 91: 1354–60.
[10]
Cillo U, Navaglia F, Vitale A, Molari A, Basso D, et al. (2004) Clinical significance of alphafetoprotein mrna in blood of patients with hepatocellular carcinoma. Clin Chim Acta 347: 129–38.
[11]
Cillo U, Vitale A, Navaglia F, Basso D, Montin U, et al. (2005) Role of blood afp mrna and tumor grade in the preoperative prognostic evaluation of patients with hepatocellular carcinoma. World J Gastroenterol 11: 6920–5.
[12]
Yao DF, Dong ZZ, Yao M (2007) Specific molecular markers in hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 6: 241–7.
[13]
Health resources and services administration (hrsa—u.s. department of health) & or gan procurement and transplantation network (optn). unos/optn policy 3.6.4.4. URL http://optn.transplant.hrsa.gov/policies？AndBylaws/policies.asp. Available at: http://optn.transplant.hrsa.gov/policies？AndBylaws/policies.asp. Accessed July 21, 2010.
[14]
Llovet JM, Brú C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the bclc staging classification. Semin Liver Dis 19: 329–38.
[15]
Cillo U, Bassanello M, Vitale A, Grigoletto FA, Burra P, et al. (2004) The critical issue of hepatocellular carcinoma prognostic classification: which is the best tool available? J Hepatol 40: 124–31.
[16]
Cillo U, Vitale A, Grigoletto F, Farinati F, Brolese A, et al. (2006) Prospective validation of the barcelona clinic liver cancer staging system. J Hepatol 44: 723–31.
[17]
Torzilli G, Donadon M, Marconi M, Palmisano A, Del Fabbro D, et al. (2008) Hepatectomy for stage b and stage c hepatocellular carcinoma in the barcelona clinic liver cancer classification: results of a prospective analysis. Arch Surg 143: 1082–90.
[18]
Wang JH, Changchien CS, Hu TH, Lee CM, Kee KM, et al. (2008) The efficacy of treatment schedules according to barcelona clinic liver cancer staging for hepatocellular carcinoma – survival analysis of 3892 patients. Eur J Cancer 44: 1000–6.
[19]
Inoue Y, Hasegawa K, Ishizawa T, Aoki T, Sano K, et al. (2009) Is there any difference in survival according to the portal tumor thrombectomy method in patients with hepatocellular carcinoma? Surgery 145: 9–19.
[20]
Ishizawa T, Hasegawa K, Aoki T, Takahashi M, Inoue Y, et al. (2008) Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 134: 1908–16.
[21]
Llovet JM, Real MI, Monta？a X, Planas R, Coll S, et al. (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359: 1734–9.
[22]
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, et al. (2008) Sorafenib in advanced hepato-cellular carcinoma. N Engl J Med 359: 378–90.
[23]
Sherman M (2008) Recurrence of hepatocellular carcinoma. N Engl J Med 359: 2045–7.
Cillo U, Vitale A, Grigoletto F, Gringeri E, D'Amico F, et al. (2007) Intention-to-treat analysis of liver transplantation in selected, aggressively treated hcc patients exceeding the milan criteria. Am J Transplant 7: 972–81.
[26]
Cillo U, Vitale A, Bassanello M, Boccagni P, Brolese A, et al. (2004) Liver transplantation for the treatment of moderately or well-differentiated hepatocellular carcinoma. Ann Surg 239: 150–9.
