A Molecular Signature to Discriminate Dysplastic Nodules From Early Hepatocellul

[Guest guest]

Gastroenterology. 2006 Sep 19; [Epub ahead of print]

A Molecular Signature to Discriminate Dysplastic Nodules From Early

Hepatocellular Carcinoma in HCV Cirrhosis.

Llovet JM, Chen Y, Wurmbach E, Roayaie S, Fiel MI, Schwartz M, Thung SN,

Khitrov G, Zhang W, Villanueva A, Battiston C, Mazzaferro V, Bruix J, Waxman

S, Friedman SL.

Mount Sinai Liver Cancer Program (Divisions of Liver Disease and

Hematology/Oncology, Department of Medicine, Recanati Transplantation

Institute, Department of Surgery; Department of Pathology), Mount Sinai

School of Medicine, New York; BCLC Group, IDIBAPS, Liver Unit. Hospital

Clinic, Barcelona, Spain; and.

BACKGROUND & AIMS: Small liver nodules approximately 2 cm are difficult to

characterize by radiologic or pathologic examination. Our aim was to

identify a molecular signature to diagnose early hepatocellular carcinoma

(HCC). METHODS: The transcriptional profiles of 55 candidate genes were

assessed by quantitative real-time reverse-transcription polymerase chain

reaction (RT-PCR) in 17 dysplastic nodules (diameter, 10 mm) and 20 early

HCC (diameter, 18 mm) from HCV cirrhotic patients undergoing

resection/transplantation and 10 nontumoral cirrhotic tissues and 10 normal

liver tissues. Candidate genes were confirmed by qualitative RT-PCR in 20

advanced HCCs and by immunohistochemistry in 75 samples and validated in an

independent set of 29 samples (dysplastic nodules [10] and small HCC [19;

diameter, 20 mm]). RESULTS: Twelve genes were significantly, differentially

expressed in early HCCs compared with dysplastic nodules (>2-fold change;

area under the receiver operating characteristic curve >/=0.8): this

included TERT, GPC3, gankyrin, survivin, TOP2A, LYVE1, E-cadherin, IGFBP3,

PDGFRA, TGFA, cyclin D1, and HGF. Logistic regression analysis identified a

3-gene set including GPC3 (18-fold increase in HCC, P = .01), LYVE1 (12-fold

decrease in HCC, P = .0001), and survivin (2.2-fold increase in HCC, P =

..02), which had a discriminative accuracy of 94%. The validity of the gene

signature was confirmed in a prospective testing set. GPC3 immunostaining

was positive in all HCCs and negative in dysplastic nodules (22/22 vs 0/14,

respectively, P < .001). Nuclear staining for survivin was positive in 12 of

13 advanced HCC cases and in 1 of 9 early tumors. CONCLUSIONS: Molecular

data based on gene transcriptional profiles of a 3-gene set allow a reliable

diagnosis of early HCC. Immunostaining of GPC3 confirms the diagnosis of

HCC.

PMID: 17087938 [PubMed - as supplied by publisher]

_________________________________________________________________

All-in-one security and maintenance for your PC. Get a free 90-day trial!

http://clk.atdmt.com/MSN/go/msnnkwlo0050000002msn/direct/01/?href=http://www.win\

dowsonecare.com/?sc_cid=msn_hotmail