pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular Carcinoma

Abstract

Hepatocarcinoma (HCC) is the fifth most common cancer, with more than one million fatalities occurring annually worldwide. Multiple risk factors are associated with HCC disease etiology, the highest incidence being in patients with chronic hepatitis B virus and hepatitis C virus, although other factors such as genetic makeup and environmental exposure are involved. Multiple genetic alterations including the activation of oncogenes and inactivation of tumor suppressor genes are required for malignancy in human cancers and are correlated with increased stages of carcinogenesis and further tumor progression. In this study of 21 HCC patients, we analyzed pRb2/p130, vascular endothelial growth factor (VEGF), p27 (KIP1) , and proliferating cell nuclear antigen as potential HCC molecular biomarkers. In our sample set, we found that p27 (KIP1) was absent. Univariate survival analysis showed that proliferating cell nuclear antigen expression (diffuse staining >50% of positive cells in tumor) was confirmed as a significant HCC prognostic biomarker for determining patient survival agreeing with previous studies (P ‫؍‬ 0.0126, log-rank test). Lower pRb2/p130 expression was associated to a borderline P value of inverse correlation with tumor malignancy and to a positive correlation with respect to the time from HCC diagnosis (Spearman coefficient ‫؍‬ 0.568; P < 0.05). Conversely, higher VEGF expression was associated with a poor survival (P ‫؍‬ 0.0257, log-rank test). We demonstrate for the first time that pRb2/p130 is inversely correlated with VEGF expression and tumor aggressiveness (P < 0.05) in p27 (KIP1) -negative HCC patients. pRb2/p130 and VEGF expression are independent from tumor staging, suggesting their possible role as independent prognostic molecular biomarkers in HCC. Furthermore, we have evidence that VEGF together with pRb2/p130 may act as new HCC biomarkers in a p27 (KIP1) -independent manner. Additional studies with larger numbers of patient data would allow the use of multivariable techniques and would be able to further identify patients with poorer survival.

RB family members as predictive and prognostic factors in human cancer

“…However, altered pRB expression appears to be significantly related to poor grade (moderately vs well differentiated, Po0.01; poorly vs moderately differentiated, Po0.001) and advanced stage (Po0.001) (Hui et al, 1999). Moreover, we recently observed that pRb2/p130 expression in HCC is independent from tumor stage, suggesting its possible role as independent prognostic molecular biomarkers (Claudio et al, 2004).…”

Vascular endothelial growth factor in the management of hepatocellular carcinoma

“…Another study of 20 patients with HCC confirmed that higher VEGF expression was associated with a lower median survival. 42 Moreover, other studies have shown that expression of VEGF in HCC was correlated with the probability of recurrence after tumor resection or ablation. [43][44][45][46] Collectively, these findings suggest that tissue VEGF expression in HCC may indicate more advanced disease and reduced median survival.…”

pRb2/p130 and VEGF expression in endometrial carcinoma in relation to angiogenesis and histopathologic tumor grade

“…12 Additionally, we have demonstrated that pRb2/p130 is inversely correlated with VEGF expression and tumor aggressiveness (p < 0.05) in p27(KIP1)-negative hepatocarcinoma (HCC) patients. 18 In this recent study it was demonstrated that pRb2/p130 and VEGF expression are independent from tumor staging, suggesting their possible role as independent prognostic molecular biomarkers in HCC. Together, these data led us to investigate the expression levels of pRb2/p130 and VEGF in endometrial carcinoma in relation to histopathologic tumor grade in a cohort of 50 patients.…”

“…12 Additionally, these clinical data are in agreement with recent studies in which we showed that VEGF and pRb2/p130 are inversely correlated in hepatocarcinoma (HCC). 18 In this study, we evaluated the correlation differences between the FIGO grading system or the binary architectural grading system and the expression levels of pRb2/p130 and VEGF in predicting the progression of endometrial carcinogenesis. The present study was conducted in 50 cases of endometrial carcinomas.…”