Loss of heterozygosity at D14S62 and D14S51 detected by a simple and non-radioactive method in plasma DNA is a potential marker of metastasis and recurrence after curative hepatic resection in hepatocellular carcinoma.
OBJECTIVE
Recurrence and metastasis in hepatocellular carcinoma remains a major challenge to further improve survival. High frequency of loss of heterozygosity at D14S62 and D14S51 in tumor tissue has been shown to be closely related to metastasis and recurrence in breast cancer. But, loss of heterozygosity on 14q in plasma and tumor tissue DNA of hepatocellular carcinoma patients has not been investigated. To establish a way to predict metastasis and recurrence after curative hepatic resection, we analyzed loss of heterozygosity on 14 q in plasma and tumor tissue DNA of hepatocellular carcinoma patients with curative resection.


METHODS
We used a simple, rapid and non-radioactive method to analyze loss of heterozygosity at D14S62 and D14S51 in paired plasma, lymphocyte and tumor tissue DNA of 85 hepatocellular carcinoma patients with curative resection.


RESULTS
From 79 cases informative for D14S62 and 78 cases informative for D14S51 of 85 hepatocellular carcinoma tissue DNA, loss of heterozygosity at D14S62 and D14S51 was present in 45 (57.0%) and 41 (52.6%) cases respectively. And in 96.0% of the tissues which showed loss of heterozygosity we were able to detect loss of heterozygosity in their matched plasma. In matched 85 cases of hepatocellular carcinoma plasma DNA, we detected loss of heterozygosity at D14S62 in 55.7% and at D14S51 in 50.0% of the respective informative DNA samples. The loss of heterozygosity patterns of plasma DNA were almost identical to their corresponding tumor tissues. A comparison of these genetic changes with clinicopathological data of these checked hepatocellular carcinoma patients showed that loss of heterozygosity at D14S62 and D14S51 was adversely correlated significantly with the presence of tumor size, with 35.4% at both the D14S62 and D14S51 locus in the HTMR (high-tendency to metastasis and recurrence) group compared with 72.9% and 59.4% in the LTMR (low-tendency to metastasis and recurrence) group at D14S62 and D14S51, respectively (P = 0.001 and P = 0.027, respectively).


CONCLUSIONS
Our results suggest that loss of heterozygosity at D14S62 and D14S51 plays an important role in the metastasis and recurrence of hepatocellular carcinoma patients following curative resection. Loss of heterozygosity at D14S62 and D14S51 in the plasma DNA of hepatocellular carcinoma patients detected by a simple and non-radioactive method has great potentials to be clinically used to predicate metastasis and recurrence after curative hepatic resection.
Liver Cancer Institute, Zhongshan Hospital, Shanghai Medical University, Shanghai, 200032, P. R. China. qiniu99@yahoo.com
Qi
Q
Niu
Zhao-You
ZY
Tang
Lun-Xiu
LX
Qin
Zeng-Chen
ZC
Ma
Lian-Hai
LH
Zhang
D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology* / Q000556:secondary / Q000601:surgery; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D019656:Loss of Heterozygosity / Q000502:physiology*; D009364:Neoplasm Recurrence, Local / Q000235:genetics*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm