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Hann et al. Urine markers for HCC monitoring

markers were either not detected (case 7), fluctuated AFP. Urine was collected at the time of diagnosis and
(case 8), or detected at low levels (cases 9 and 10). treatment with microwave ablation [Figure 1D]. The
DNA marker mGSTP1 was highly elevated in urine at
Case 1 the time of HCC diagnosis. Two months after treatment,
A 68-year-old male underwent transarterial both urine mGSTP1 and serum AFP levels decreased
chemoembolization (TACE) for HCC. Six years later, to the normal range while urine mRASSF1A was
he showed tumor recurrence (Pos) by MRI. Urine elevated. At the next visit 3 months later, mRASSF1A
specimens were obtained at 6 and 3 months prior to decreased but remained detectable while the two other
the MRI confirmation of recurrence (indicated as -6, DNA markers, TP53m and mGSTP1 increased. Four
-3 on the X-axis, Figure 1A). In the urine specimens, months later, an MRI detected a recurrent tumor (solid
TP53m and mRASSF1A markers were detected at 6 lesion). Unfortunately, the urine was not collected at
months prior and increased at 3 months before MRI “-2” and at the time of diagnosis “Pos”, hence there is
detection of recurrence. Unfortunately urine is missing no marker data available at these time points.
at the time of MRI imaging. His serum AFP levels
remained at 2 ng/mL throughout the study, indicating Case 5
the tumor was AFP-negative. He later received liver A 56-year-old male underwent TACE for HCC. Urine
[36]
transplant. was collected on the day of treatment and at a follow-
up visit 1 month later [Figure 1E]. The mRASSF1A
Case 2 marker was detected in the urine on the day of TACE
A 73-year-old male underwent TACE for HCC. Urine treatment, and the levels of mRASSF1A in the urine
samples were collected after the treatment and during dropped one month following treatment. Similarly,
the follow-up period of 12 months when the tumor serum AFP levels decreased nearly 10-fold from
recurred [Figure 1B]. Three months after the initial 3,770 ng/mL to 323 ng/mL. However, MRI 4 months
TACE treatment (indicated by a black arrow on the later detected HCC recurrence and increased levels
X-axis), TP53m and mRASSF1A levels were elevated of serum AFP (1,522 ng/mL). No urine samples were
while serum AFP had returned to a baseline level collected at this time point or later. Despite receiving
of 5.3 ng/mL from 88.9 ng/mL at the time of TACE another TACE treatment, the patient passed away 8
treatment. These two urine DNA markers dropped to months later.
baseline on the next visit 3 months later. The TP53m
and serum AFP levels rose again about 3 months prior Case 6
to the detection of recurrence by MRI. At the time of A 56-year-old male with HCC underwent TACE.
detection of the second recurrence (marked “Pos”), Urine samples were collected at 3 and 4 years after
both TP53m and mRASSF1A levels were elevated. TACE. mRASSF1A was found elevated at 3 years and
Serum AFP level was at 36.4 ng/mL, indicating a negative at 4 years post TACE. The patient has had no
rise from the baseline. Two months after the second recurrence [Figure 1F]. AFP was in normal range. The
treatment, serum AFP, TP53 and mRASSF1A all patient was lost for follow up.
decreased. The patient did not return after this visit.
Case 7
Case 3 A 58-year-old male with HCC received TACE followed
A 55-year-old male with a 4-cm HCC received TACE. by radiofrequency ablation (RFA). Urine collection
The tumor recurred 5 years later, which was treated started 1 year after RFA. No biomarkers were detected
with microwave ablation (indicated by the black arrow 2 years post RFA, as the patient remained recurrence
on the X-axis; Figure 1C). The tumor recurred again free [Figure 1G].
during a follow up appointment 3 months later (marked
“Pos”; Figure 1C). Urine DNA markers at two visits Case 8
prior to the first recurrence were below the level of A 62-year-old male with HCC received RFA. Urine
detection. However, mGSTP1 was elevated 1 month samples were collected on the day of treatment and
after microwave treatment. Interestingly, when the every three months after for 9 months [Figure 1H].
tumor recurred for a second time (1.6 cm) 3 months Serum AFP, TP53 mutation, and mRASSF1A levels
after treatment, the mGSTP1 was undetectable were all elevated on the day of RFA, and decreased 3
while TP53m was elevated. This may indicate the and 6 months following the treatment to below the limit
heterogeneity of HCC. Note, the serum AFP levels of detection. There has been no recurrence by MRI.
were below 20 ng/mL in the period of study.
Case 9
Case 4 A 27-year-old female was diagnosed with HCC at age
A 54-year-old male diagnosed with HCC and elevated 20 and the original tumor was treated 3 times with
108 Hepatoma Research ¦ Volume 3 ¦ June 6, 2017