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Wang et al. Hepatoma Res 2018;4:14 I http://dx.doi.org/10.20517/2394-5079.2018.16 Page 3 of 10

Figure 2. Mechanism of clonal origin with IM type and MO type in recurrent hepatocellular carcinoma/multinodular hepatocellular
carcinoma. P: primary hepatocellular carcinoma; IM: intrahepatic metastasis; MO: multicentric occurrence

Remarkably, the incidence of MVI in single nodule HCC and MHCC are 40.4% and 55.6%, respectively.
Higher incidence of MVI in MHCC indicates the possibility of IM type clonal origin in MHCC; MO
type HCC is derived from the continuous blow of inflammation and fibrosis. Among the pathogenesis of
inflammation, hepatitis viral is the most important reason and the most common cause of HCC. According
to our statistics of 30 years’ HCC patients in the Eastern Hepatobiliary Surgery Hospital, the infection rate
of hepatitis B virus (HBV) and hepatitis C virus (HCV) was 85.86% and 9.76%, respectively . Therefore,
[26]
effective inhibition of hepatitis virus replication is a key factor in the prevention of the occurrence of MO
type HCC [Figure 2].

With the theory about the origination of malignant tumor constant improvement, such as tumor
heterogeneity, cancer stem cells, circulating tumor cells, increased evidence suggests that there may be more
complex clonal origin patterns in malignant tumor [27-29] . For example, heterogeneous clonal origin in single
nodule HCC and IM-MO mixed clonal origin in RHCC and MHCC [30-32] . HCC with different clonal origin
may engender variant clinical prognosis and therefore, different therapy method [33,34] . Consequently, it is a
crucial cooperation for hepatic surgery and molecular pathology to formulate rational treatment strategy for
RHCC and MHCC with different clonal origin.

THE CLONAL ORIGIN OF RHCC
The postoperative recurrence of HCC is likely to be an important indication of enhanced invasiveness of
HCC and poor prognosis . As a result, the current treatment strategy for primary HCC may not be suitable
[35]
for RHCC. In view of this, scholars established many assessment systems for the prognosis of RHCC [36-41] .
However, many studies focused on exploring the rational treatment of RHCC did not screen out the suitable
groups for traditional treatments, such as hepatic resection, liver transplantation, transhepatic arterial chem
otherapy and embolization (TACE), and radiofrequency ablation (RFA) [42-45] . It may attribute to the ignorance
of great impact of clonal origin on the prognosis of patients.

Therefore, studies based on pathomorphology to predict the clonal origin of RHCC suggested that the
incidence of IM type and MO type HCC is about 60% and 40%, respectively; IM type RHCC has poorer
prognosis than MO type RHCC. Meanwhile, MO type RHCC and IM type RHCC are suitable for hepatic
resection and TACE, respectively [46-48] . Based on above studies, to some extent, it is meaningful to judge the
clonal origin of RHCC by histopathology. However, the experience of pathologist may affect the judgment
of the clonal origin pattern. Therefore, histopathology cannot objectively and quantitatively reflect the real
biological behavior of RHCC. To sum up, it is necessary for us to establish therapeutic strategy for RHCC
with different clonal origin according to molecular pathological examination, so as to enable patients to get
the best prognosis.