Background & Aims: The study aimed to evaluate the tissue expression of molecules involved in intracellular signalling pathways as predictors of response to sorafenib in advanced hepatocellular carcinoma (HCC). Methods: We considered 77 patients enrolled into three prospective trials of sorafenib treatment for whom pretreatment tumour tissue was available. The tissue expression of beta-catenin, glutamine synthetase (GS), phosphorylated extracellular signal regulated kinase (pERK), phosphorylated v-akt murine thymoma viral oncogene homolog (pAKT) and vascular endothelial growth factor receptor-2 (VEGFR-2) was analysed by immunostaining. Stains were scored semiquantitatively and compared with a reference group of 56 untreated HCCs. Results: Overall, the expression of antigens was comparable between treated and untreated patients. Shorter progression-free survival (PFS) and overall survival (OS) were associated with increased pERK staining (>= 2+ scores) (PFS: 75th percentile 4.4 vs 8.4 months; P = 0.01; OS: 75th percentile 7.0 vs 15.0 months; P = 0.005) and VEGFR-2 staining (>= 2+ scores) (PFS: 75th percentile 3.8 vs 7.0 months; P = 0.039; OS: 75th percentile 6.3 vs 15.0 months; P = 0.004). At multivariate analysis, both pERK and VEGFR-2 staining maintained an independent effect on OS (HR 2.09; 95% CI, 1.13-3.86, P = 0.019 and HR 2.28; 95% CI, 1.13-4.61, P = 0.021 respectively). No effect was observed for the other tested biomarkers. Conclusions: Elevated tissue expression of pERK and VEGFR-2 was predictive of poor outcome in advanced HCC treated with sorafenib.
Expression of pERK and VEGFR-2 in advanced hepatocellular carcinoma and resistance to sorafenib treatment / Negri, F. V.; Dal Bello, B.; Porta, C.; Campanini, N.; Rossi, S.; Tinelli, C.; Poggi, G.; Missale, G.; Fanello, S.; Salvagni, S.; Ardizzoni, A.; Maria, S. E.. - In: LIVER INTERNATIONAL. - ISSN 1478-3223. - 35:8(2015), pp. 2001-2008. [10.1111/liv.12778]
Expression of pERK and VEGFR-2 in advanced hepatocellular carcinoma and resistance to sorafenib treatment
Negri F. V.;Porta C.;Campanini N.;Missale G.;
2015-01-01
Abstract
Background & Aims: The study aimed to evaluate the tissue expression of molecules involved in intracellular signalling pathways as predictors of response to sorafenib in advanced hepatocellular carcinoma (HCC). Methods: We considered 77 patients enrolled into three prospective trials of sorafenib treatment for whom pretreatment tumour tissue was available. The tissue expression of beta-catenin, glutamine synthetase (GS), phosphorylated extracellular signal regulated kinase (pERK), phosphorylated v-akt murine thymoma viral oncogene homolog (pAKT) and vascular endothelial growth factor receptor-2 (VEGFR-2) was analysed by immunostaining. Stains were scored semiquantitatively and compared with a reference group of 56 untreated HCCs. Results: Overall, the expression of antigens was comparable between treated and untreated patients. Shorter progression-free survival (PFS) and overall survival (OS) were associated with increased pERK staining (>= 2+ scores) (PFS: 75th percentile 4.4 vs 8.4 months; P = 0.01; OS: 75th percentile 7.0 vs 15.0 months; P = 0.005) and VEGFR-2 staining (>= 2+ scores) (PFS: 75th percentile 3.8 vs 7.0 months; P = 0.039; OS: 75th percentile 6.3 vs 15.0 months; P = 0.004). At multivariate analysis, both pERK and VEGFR-2 staining maintained an independent effect on OS (HR 2.09; 95% CI, 1.13-3.86, P = 0.019 and HR 2.28; 95% CI, 1.13-4.61, P = 0.021 respectively). No effect was observed for the other tested biomarkers. Conclusions: Elevated tissue expression of pERK and VEGFR-2 was predictive of poor outcome in advanced HCC treated with sorafenib.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
