Determination of clonal origin of recurrent hepatocellular carcinoma for personalized therapy and outcomes evaluation: a new strategy for hepatic surgery.
BACKGROUND
Recurrent hepatocellular carcinoma (RHCC) after curative resection is a major challenge for hepatic surgeons. A better understanding of the clonal origin of RHCC will help clinicians design personalized therapy and assess postoperative outcomes. The current study was performed to determine the clonal origin of RHCC and its clinical significance.


STUDY DESIGN
Fifteen high-frequency of loss of heterozygosity of DNA microsatellites were determined on 100 tumor nodules in 60 matched pairs of RHCC from 40 patients who underwent liver re-resections. The relationships among the origin of clonal patterns of RHCC and the surgicopathologic features and clinical outcomes were analyzed.


RESULTS
Of 60 pairs of RHCC, there were 2 clonal patterns with 6 subclonal types. Pattern I was multicentric occurrence (MO type) in 14 pairs (23.3%) and pattern II was intrahepatic metastasis (IM type) in 46 pairs (76.7%). The clinicopathologic features, including recurrence time, tumor size, vascular invasion, histological grading, and associated chronic liver diseases in patients with the MO type of RHCC were significantly different from those with the IM type of RHCC (p < 0.05 to 0.001). Compared with patients in the IM group, patients in the MO group had significantly better overall survival (130.8 ± 8.5 months vs 80.8 ± 8.5 months; p < 0.05) and recurrence-free survival (33.8 ± 4.5 months vs 14.2 ± 2.5 months; p < 0.001).


CONCLUSIONS
The MO-type RHCC was closely associated with better postoperative outcomes when compared with the IM-type RHCC. Generally, we recommend liver re-resection for MO-type RHCC, and interventional therapy for IM-type RHCC. Microdissection-based microsatellite loss of heterozygosity protocol has advantages in assessing the clonal origin, modes of personalized treatment, and clinical outcomes of RHCC.
['Wang|Bin|B|', 'Xia|Chun-Yan|CY|', 'Lau|Wan-Yee|WY|', 'Lu|Xin-Yuan|XY|', 'Dong|Hui|H|', 'Yu|Wen-Long|WL|', 'Jin|Guang-Zhi|GZ|', 'Cong|Wen-Ming|WM|', 'Wu|Meng-Chao|MC|']
D000328:Adult D006528:Carcinoma, Hepatocellular D002999:Clone Cells D005260:Female D005819:Genetic Markers D006498:Hepatectomy D006801:Humans D008113:Liver Neoplasms D019656:Loss of Heterozygosity D008297:Male D018895:Microsatellite Repeats D008875:Middle Aged D009364:Neoplasm Recurrence, Local D018807:Polymorphism, Single-Stranded Conformational D057285:Precision Medicine D012189:Retrospective Studies D016019:Survival Analysis D016896:Treatment Outcome
recurrent hepatocellular carcinoma hepatocellular carcinoma RHCC loss of heterozygosity multicentric occurrence MO intrahepatic metastasis IM HCC LOH PCR polymerase chain reaction