Qualitative α-fetoprotein Seroconversion In Recurrence Of Hepatocellular Carcinoma Following Hepatectomy

Alpha-fetoprotein (AFP), a member of the albuminoid multigene family,is abundantly expressed in the fetal yolk sac and liver, but not in normaladult tissues, whereas AFP expression resurges during liver regenerationand in hepatocellular carcinoma(HCC)。AFP is the most important and wildly used serum biomarker of themalignancy. In recent years, studies have shown that serum AFP level isalso related to the prognosis of HCC. AFP positive patients have worseprognosis than AFP negative patients.The mechanisms that HCC produces AFP have not yet been fullyrevealed. The AFP elevation in HCC has been shown to correlate with poortumor differentiation, tumor burden, early recurrence after tumor resection.However, cumulative evidence has shown that AFP plays an important rolein the regulation of tumor growth and cell differentiation and can stimulateproliferation of human hepatoma cells.In general, HCC recurrent rate is quite high and even up to70%at5year even through curative treatment. HCC will keep its original AFPquality when it recurs. But in fact, we clinically observed that somepatients with recurrent HCC might not maintain the original positivity ornegativity. We are not able to make sure whether such phenomenon, wenamed it as “qualitative AFP seroconversion”, is exactly existence andspecific for HCC recurrence. We aim to verify whether “qualitative AFPseroconversion” is present in recurrent hepatocellular carcinoma (HCC)and its impact on prognosis.，Material and methods: A total of512consecutive patients withrecurrent HCC following partial keratectomy was enrolled at the EasternHepatobiliary Surgery Hospital (EHBH) between September2005and May2010. AFP>400and <20ng/ml as positive and negative limits was used tomeasure the quality at initial and recurrent stage: group PP, AFP＞400ng/ml both at initiation and recurrence(n=142); group NN, AFP≤20ng/ml both at initiation and recurrence(n=267); group NP, AFP <20ng/ml at initiation and>400ng/ml at recurrence(n=41); group PN, AFP>400ng/ml at initiation and <20ng/ml at recurrence(n=62).The initial andrecurrent clinical characteristics, overall survival (OS), time to recurrence (TTR), and recurrence-to-death survival (RTDS) were compared among thefour groups.Results: Further comparision on liver function, HBV-DNA load andAFP decline indicate the AFP seroconversion is specific for HCCrecurrence other than underlying disease. Group PP had significantlyincreased numbers of patients with HCC of primary tumor diameter(P=0.009), incompleted encupsule (P<0.001), Edmondson-Steiner grade ofIII-IV (P<0.001), and microvascular invasion (P<0.001) than in those theother three groups. Patients in group PP or group NN had a shorter orlonger OS and RTDS. There was no statistically difference in OS, TTR andRTDS between group NN and group PN patients (p=0.631,0.663,0.466,respectively). Patients in group PP had significantly decreased OScompared with those group NN (P=0.012) and similar RTDS with thosegroup NP (P=0.273). However, patients in group NP and group PNproduced a significantly prolonged TTR than those group NN and groupPP.Conclusion:1. The qualitative AFP seroconversion is indeed exist in patients withrecurrent HCC.2. HCC patients with persistent AFP positive (group PP) and negative(group NN) produced the worst and best prognosis3. AFP negative conversion (group PN) might predicts a better RTDS,refine the prognosis; AFP positive conversion (group NP) might indicatesan even worse RTDS, worsen the prognosis.In conclusion, AFP seroconversion seems to be an important prognosticfactors for recurrent HCC.