2018, Number 6
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Ann Hepatol 2018; 17 (6)
Clinicopathological Distinction of Low-AFP-Secreting vs. High-AFP-Secreting Hepatocellular Carcinomas
Gurakar A, Garonzik-Wang MMJ, Kim A, Anders RA, Oshima K, Georgiades C, Gurakar M, Ottmann S, Cameron AM, Philosophe B, Saberi B
Language: English
References: 46
Page: 1052-1066
PDF size: 801.87 Kb.
ABSTRACT
Introduction and aims. We aimed to investigate the clinical and pathological differences between low-AFP-secreting (AFP ‹ 20
ng/mL) and high-AFP-secreting (AFP ≥ 20 ng/mL) hepatocellular carcinomas in patients who undergo liver transplant (LT).
Material
and methods. We evaluated 145 patients who underwent deceased donor LT for HCC from January 1, 2005 until August 1, 2015
at the Johns Hopkins Hospital.
Results. Median pre-LT AFP in the entire cohort was 13 ng/mL (IQR 6-59). Using serum AFP cutoff
of 20 ng/mL, 61 (42%) patients had high-AFP-secreting tumors and 84 (58%) had low-AFP-secreting tumors. Patients with high-
AFP-secreting tumors had larger lesions (3 cm
vs. 2.4 cm, p = 0.024), and were more likely to have microvascular-invasion (36.1%
vs. 20.2%, p = 0.02) and poor-differentiation (18%
vs. 4.8%, p = 0.01), and tumor recurrence following LT (28%
vs. 6%, p ‹ 0.001).
The 1-year, 3-year, and 5-year recurrence-free survival for patients in the low-AFP-secreting group compared to the high-AFP-secreting
group were 100%, 92%, 92%
vs. 81.3%, 71.3%, 68.5% respectively (p = 0.0003).
Conclusion. AFP is a suboptimal predictor
of tumor recurrence following liver transplant in HCC patients. However, it can have some value in distinguishing more
aggressive forms of HCC (high-AFP-secreting) that are associated with higher tumor recurrence. Novel tumor biomarkers are needed
that can enhance predicting tumor recurrence following LT based on tumor biology.
REFERENCES
Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334: 693-9.
Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, Ascher NL, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001; 33: 1394-403.
Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 2009; 10: 35-43.
Halazun KJ, Najjar M, Abdelmessih RM, Samstein B, Griesemer AD, Guarrera JV, Kato T, et al. Recurrence After Liver Transplantation for Hepatocellular Carcinoma: A New MORAL to the Story. Ann Surg 2017; 265: 557-64.
Agopian VG, Harlander-Locke M, Zarrinpar A, Kaldas FM, Farmer DG, Yersiz H, Finn RS, et al. A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation: analysis of 865 consecutive liver transplant recipients. J Am Coll Surg 2015; 220: 416-27.
Trevisani F, D’Intino PE, Morselli-Labate AM, Mazzella G, Accogli E, Caraceni P, Domenicali M, et al. Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol 2001; 34: 570-5.
Daniele B, Bencivenga A, Megna AS, Tinessa V. Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma. Gastroenterology 2004; 127: S108-112.
Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, Duca P. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol 2006; 101: 513-23.
Gupta S, Bent S, Kohlwes J. Test characteristics of alphafetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. A systematic review and critical analysis. Ann Intern Med 2003; 139: 46-50.
Hanazaki K, Kajikawa S, Koide N, Adachi W, Amano J. Prognostic factors after hepatic resection for hepatocellular carcinoma with hepatitis C viral infection: univariate and multivariate analysis. Am J Gastroenterol 2001; 96: 1243-50.
Charriere B, Maulat C, Suc B, Muscari F. Contribution of alpha- fetoprotein in liver transplantation for hepatocellular carcinoma. World J Hepatol 2016; 8: 881-90.
Peng SY, Chen WJ, Lai PL, Jeng YM, Sheu JC, Hsu HC. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and betacatenin mutations. Int J Cancer 2004; 112: 44-50.
Furihata T, Sawada T, Kita J, Iso Y, Kato M, Rokkaku K, Shimoda M, et al. Serum alpha-fetoprotein level per tumor volume reflects prognosis in patients with hepatocellular carcinoma after curative hepatectomy. Hepatogastroenterology 2008; 55: 1705-9.
Tateishi R, Shiina S, Yoshida H, Teratani T, Obi S, Yamashiki N, Yoshida H, et al. Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers. Hepatology 2006; 44: 1518-27.
Shao YY, Lin ZZ, Hsu C, Shen YC, Hsu CH, Cheng AL. Early alpha-fetoprotein response predicts treatment efficacy of antiangiogenic systemic therapy in patients with advanced hepatocellular carcinoma. Cancer 2010; 116: 4590-6.
Liu L, Zhao Y, Jia J, Chen H, Bai W, Yang M, Yin Z, et al. The Prognostic Value of Alpha-Fetoprotein Response for Advanced- Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization. Sci Rep 2016; 6: 19851.
Han K, Tzimas GN, Barkun JS, Metrakos P, Tchervenkov JL, Hilzenrat N, Wong P, et al. Preoperative alpha-fetoprotein slope is predictive of hepatocellular carcinoma recurrence after liver transplantation. Can J Gastroenterol 2007; 21: 39-45.
Berry K, Ioannou GN. Serum alpha-fetoprotein level independently predicts posttransplant survival in patients with hepatocellular carcinoma. Liver Transpl 2013; 19: 634-45.
Hakeem AR, Young RS, Marangoni G, Lodge JP, Prasad KR. Systematic review: the prognostic role of alpha-fetoprotein following liver transplantation for hepatocellular carcinoma. Aliment Pharmacol Ther 2012; 35: 987-99.
Zhou L, Liu J, Luo F. Serum tumor markers for detection of hepatocellular carcinoma. World J Gastroenterol 2006; 12: 1175-81.
Hsu CY, Liu PH, Lee YH, Hsia CY, Huang YH, Lin HC, Chiou YY, et al. Using serum alpha-fetoprotein for prognostic prediction in patients with hepatocellular carcinoma: what is the most optimal cutoff? PLoS One 2015; 10: e0118825.
Morinaga T, Sakai M, Wegmann TG, Tamaoki T. Primary structures of human alpha-fetoprotein and its mRNA. Proc Natl Acad Sci U S A 1983; 80: 4604-8.
Johnson PJ, Poon TC, Hjelm NM, Ho CS, Ho SK, Welby C, Stevenson D, et al. Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and nonseminomatous germ cell tumour. Br J Cancer 1999; 81: 1188-95.
Gitlin D, Perricelli A, Gitlin GM. Synthesis of -fetoprotein by liver, yolk sac, and gastrointestinal tract of the human conceptus. Cancer Res 1972; 32: 979-82.
Marrero JA, Lok AS. Newer markers for hepatocellular carcinoma. Gastroenterology 2004; 127: S113-119.
Lok AS, Lai CL. alpha-Fetoprotein monitoring in Chinese patients with chronic hepatitis B virus infection: role in the early detection of hepatocellular carcinoma. Hepatology 1989; 9: 110-115.
Sato Y, Nakata K, Kato Y, Shima M, Ishii N, Koji T, Taketa K, et al. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N Engl J Med 1993; 328: 1802-6.
Doherty AP, Bower M, Christmas TJ. The role of tumour markers in the diagnosis and treatment of testicular germ cell cancers. Br J Urol 1997; 79: 247-52.
Mehta N, Dodge JL, Roberts JP, Yao FY. Validation of the prognostic power of the RETREAT score for hepatocellular carcinoma recurrence using the UNOS database. Am J Transplant 2018; 18(5): 1206-13.
Sterling RK, Jeffers L, Gordon F, Venook AP, Reddy KR, Satomura S, Kanke F, et al. Utility of Lens culinaris agglutininreactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol 2009; 7: 104-13.
Panduro A, Shalaby F, Weiner FR, Biempica L, Zern MA, Shafritz DA. Transcriptional switch from albumin to alpha-fetoprotein and changes in transcription of other genes during carbon tetrachloride induced liver regeneration. Biochemistry 1986; 25: 1414-20.
Agopian VG, Harlander-Locke MP, Markovic D, Zarrinpar A, Kaldas FM, Cheng EY, Yersiz H, et al. Evaluation of Patients With Hepatocellular Carcinomas That Do Not Produce alpha- Fetoprotein. JAMA Surg 2017; 152: 55-64.
Llovet JM, Villanueva A, Lachenmayer A, Finn RS. Advances in targeted therapies for hepatocellular carcinoma in the genomic era. Nat Rev Clin Oncol 2015; 12: 408-24.
Hoshida Y, Nijman SM, Kobayashi M, Chan JA, Brunet JP, Chiang DY, Villanueva A, et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 2009; 69: 7385-92.
Sia D, Villanueva A, Friedman SL, Llovet JM. Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis. Gastroenterology 2017; 152: 745-61.
Roskams TA, Libbrecht L, Desmet VJ. Progenitor cells in diseased human liver. Semin Liver Dis 2003; 23: 385-96.
Maximin S, Ganeshan DM, Shanbhogue AK, Dighe MK, Yeh MM, Kolokythas O, Bhargava P, et al. Current update on combined hepatocellular-cholangiocarcinoma. Eur J Radiol Open 2014; 1: 40-8.
Fowler KJ, Sheybani A, Parker RA, Doherty S, E MB, Chapman WC, Menias CO. Combined hepatocellular and cholangiocarcinoma (biphenotypic) tumors: imaging features and diagnostic accuracy of contrast-enhanced CT and MRI. AJR Am J Roentgenol 2013; 201: 332-9.
Ma WJ, Wang HY, Teng LS. Correlation analysis of preoperative serum alpha-fetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy. World J Surg Oncol 2013; 11: 212.
Yamashita T, Forgues M, Wang W, Kim JW, Ye Q, Jia H, Budhu A, et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res 2008; 68: 1451-61.
Hameed B, Mehta N, Sapisochin G, Roberts JP, Yao FY. Alpha- fetoprotein level > 1,000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria. Liver Transpl 2014; 20: 945-51.
Chan EY, Larson AM, Fix OK, Yeh MM, Levy AE, Bakthavatsalam R, Halldorson JB, et al. Identifying risk for recurrent hepatocellular carcinoma after liver transplantation: implications for surveillance studies and new adjuvant therapies. Liver Transpl 2008; 14: 956-65.
Roayaie S, Schwartz JD, Sung MW, Emre SH, Miller CM, Gondolesi GE, Krieger NR, et al. Recurrence of hepatocellular carcinoma after liver transplant: patterns and prognosis. Liver Transpl 2004; 10: 534-40.
Guerrero-Misas M, Rodriguez-Peralvarez M, De la Mata M. Strategies to improve outcome of patients with hepatocellular carcinoma receiving a liver transplantation. World J Hepatol 2015; 7: 649-61.
Marshall AE, Rushbrook SM, Vowler SL, Palmer CR, Davies RJ, Gibbs P, Davies SE, et al. Tumor recurrence following liver transplantation for hepatocellular carcinoma: role of tumor proliferation status. Liver Transpl 2010; 16: 279-88.
Guzman G, Alagiozian-Angelova V, Layden-Almer JE, Layden TJ, Testa G, Benedetti E, Kajdacsy-Balla A, et al. p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients. Mod Pathol 2005; 18: 1498-503.