ESM-1 expression in stromal cells is predictive of recurrence after radiofrequency ablation in early hepatocellular carcinoma.
OBJECTIVE
The prognosis of hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA) is mainly linked to tumor recurrence. So far, no tissue biomarker of recurrence has been validated in biopsy samples. We aimed at investigating the prognostic value of tissue biomarkers in HCC biopsy samples of patients treated with RFA.


METHODS
All consecutive naive patients from 3 university hospitals, with compensated cirrhosis, early-stage (BCLC 0/A) uninodular HCC treated with RFA, and available tumor biopsy, were included. Edmondson's grade, and the expression of cytokeratin 19, glutamine synthase, beta-catenin, epithelial cell adhesion molecule (EpCAM), and endothelial cell-specific molecule 1 (ESM-1) were assessed. Main clinical end points were overall and early recurrence. Statistical analyses were performed using Kaplan Meier, Log-rank test, and Cox models.


RESULTS
150 patients were included. Recurrence, death or liver transplantation occurred in 85, 51, and 12 patients, respectively. Median follow-up was 27months. ESM-1 expression by HCC stromal endothelial cells was observed in 58 patients (40%) and was associated with higher serum AFP levels, larger tumor, and more frequent expression of EpCAM and surrogate markers of activation of the Wnt-ß-catenin pathway. The 2 independent predictive factors of overall recurrence were serum AFP (HR 1.11 [1.002; 1.22], p=0.045) and ESM-1 expression (HR 1.56 [1.004; 2.43], p=0.048). ESM-1 expression was also an independent predictive factor of early recurrence (HR 1.81 [1.02; 3.21], p=0.042).


CONCLUSIONS
ESM-1 expression by stromal endothelial cells, in tumor biopsy samples, has an independent predictive value of early recurrence after RFA.
Service d'Anatomie pathologique, Groupe hospitalier Paris-Seine-Saint Denis, Hôpital Jean Verdier, AP-HP, 93143 Bondy, France; Université Paris 13, Sorbonne Paris Cité, UFR SMBH, F-93000 Bobigny, France.
Marianne
M
Ziol
Angela
A
Sutton
Julien
J
Calderaro
Nathalie
N
Barget
Mounir
M
Aout
Vincent
V
Leroy
Jean-Frédéric
JF
Blanc
Nathalie
N
Sturm
Paulette
P
Bioulac-Sage
Pierre
P
Nahon
Jean-Charles
JC
Nault
Nathalie
N
Charnaux
Gisèle
G
N'kontchou
Jean-Claude
JC
Trinchet
Maryse
M
Delehedde
Olivier
O
Seror
Michel
M
Beaugrand
Eric
E
Vicaut
Nathalie
N
Ganne-Carrié
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000601:surgery*; D017115:Catheter Ablation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology*; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D011509:Proteoglycans / Q000032:analysis / Q000502:physiology*; D017154:Stromal Cells / Q000737:chemistry*
C101134:ESM1 protein, human; D009363:Neoplasm Proteins; D011509:Proteoglycans
AFP; CT; ESM-1; Early hepatocellular carcinoma; Endocan; EpCAM; HCC; Immunohistochemistry; K; LT; Liver biopsy; MRI; Microvascular invasion; RFA; Radiofrequency ablation; Tissue biomarkers; alpha-foetoprotein; computed tomodensitometry; cytokeratin; endothelial cell-specific molecule 1; epithelial cell adhesion molecule; hepatocellular carcinoma; liver transplantation; magnetic resonance imaging; radiofrequency ablation