Detection and clinical significance of bone marrow micrometastases in patients undergoing liver transplantation for hepatocellular carcinoma.
BACKGROUND
Existing methods of selecting patients with hepatocellular carcinoma (HCC) for liver transplantation rely on computed tomography and magnetic resonance imaging, which fail to detect vascular invasion or micrometastases. Vascular invasion cannot be assessed pretransplant because of the risks of tumor biopsy. Pretransplant detection of micrometastases in bone marrow is an alternative method that may identify patients at risk of recurrence and permit better organ allocation. The authors' aim was to develop an accurate method of detecting hepatocellular carcinoma micrometastases that may have a clinical role in pretransplant assessment.


METHODS
Iliac crest bone marrow was sampled from 18 patients with HCC (before liver transplantation) and 14 controls (cirrhosis, 9; hematologic disorders, 5). Mononuclear bone marrow fractions were evaluated for the presence of micrometastases by immunocytochemistry (ICC) using Hep Par-1 (HPICC) and Glypican-3 (GPICC), and by reverse-transcriptase (RT) polymerase chain reaction using two primer pairs targeting albumin (Alb1RT and Alb2RT) and one pair targeting alpha-fetoprotein (AFPRT). Each marker was compared in terms of (1) specificity and (2) positive and negative predictive values for tumor recurrence.


RESULTS
The specificity of each marker for detecting HCC micrometastases were as follows: HPICC, 93%; GPICC, 92%; Alb1RT, 33%; Alb2RT, 59%; and AFPRT, 0%. The positive (negative) predictive values for HPICC, GPICC, and Alb2RT for posttransplant tumor recurrence were 42% (100%), 40% (73%), and 0% (43%), respectively. HPICC-positive micrometastases were identified in all patients with postoperative tumor recurrence (n=5) and in 75% of patients with microscopic vascular invasion.


CONCLUSIONS
Detection of HCC micrometastases in bone marrow of potential liver transplant candidates is a potentially useful technique that may provide important prognostic information without the need for preoperative tumor biopsy. The authors' preliminary data indicate that HPICC is a promising immunocytochemical marker for HCC micrometastases, and larger studies are needed to confirm its clinical role.
Sutcliffe
Robert
R
Liver Transplant Unit, King's College Hospital, London, United Kingdom.
Maguire
Donal
D
Murphy
Philip
P
Portmann
Bernard
B
Rela
Mohamed
M
O'Sullivan
Gerald
G
Mufti
Ghulam
G
Heaton
Nigel
N
D000199:Actins / Q000235:genetics; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001707:Biopsy, Needle; D001853:Bone Marrow / Q000473:pathology*; D002102:Cadaver; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000601:surgery*; D017931:DNA Primers; D005260:Female; D006402:Hematologic Diseases / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology* / Q000601:surgery*; D016031:Liver Transplantation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors
D000199:Actins; D017931:DNA Primers