Immunohistochemical Expression of Vascular Endothelial Growth Factor A in Advanced Gallbladder Carcinoma

Abstract

Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The molecular mechanisms involved in the pathogenesis of GBC remain poorly understood. The vascular endothelial growth factor A (VEGF-A) is a potent proangiogenic agent involved in the carcinogenesis of many human tumors and is an attractive target for cancer therapy. We characterized VEGF-A expression in advanced GBC and its relation to clinicopathologic features. VEGF-A expression was examined by immunohistochemistry in tissue microarrays containing 224 advanced gallbladder carcinomas and 39 chronic cholecystitis. The cases were classified as low or high expression to evaluate the association of VEGF-A expression level with clinicopathologic variables. The Kaplan-Meier method was used to estimate survival as a function of time, and survival differences were analyzed by the log-rank test. High expression of VEGF-A was observed in 81% (183/224) of tumors and 5.1% (2/39) of chronic cholecystitis (P<0.0001). The VEGF-A expression had a significant relationship with histologic grade and TNM stage (P<0.05). Moreover, 5-year survival analysis indicated that high expression of VEGF-A is associated with a poor prognosis in patients with advanced GBC (P=0.0116). Our results indicate that VEGF-A is highly expressed in GBC and correlates with poor prognosis, suggesting that VEGF-A expression could be used as a biomarker for predicting malignant behavior and for identifying a subset of patients who may benefit from anti-VEGF-A therapies.

VEGF expression in pancreatic cancer and other malignancies: a review of the literature

“…It might be a predictive factor for advanced-stage disease [64]. VEGF-A is highly expressed in gallbladder carcinoma and correlates with poor prognosis, suggesting that VEGF-A expression could be used as a biomarker for predicting malignant behavior and for identifying a subset of patients who may benefit from anti-VEGF-A therapies [65]. VEGF-D plays, also, an important role in gallbladder cancer progression [66].…”

Adenocarcinoma of the Gallbladder: Biology of Disease, Prognosticators, and Staging

“…In a fraction of CG showing augmented angiogenesis, vascular endothelial growth factor/VEGF is expressed (Yamamoto et al 1998;Giatromanolaki et al 2003). The presence and expression level of VEGF were associated with tumor size, lymphatic invasion, and advanced disease stage (Okita et al 1998;Letelier et al 2014). Expression of plateletderived endothelial growth factor/thymidine phosphorylase was detected in 63 % of CG, while hyperplastic epithelia or adenomas did not show significant expression.…”

Targeting specific molecular pathways holds promise for advanced gallbladder cancer therapy

“…5% [109]. 20 Overexpression 58.3% [122] Early event, decreased overall survival [122] Angiogenesis pathway VEGF-A Overexpression 81% [132], 53.6% [134], 63.3% [135] Poor prognosis [132,134], predict tumor vascularity [135] VEGF-C Overexpression 64% [131] Lymph node metastasis [131] VEGF-D Overexpression 62% [131] Lymph node metastasis [131] carcinogenesis and cancer maintenance [52]. The role of abnormal activation of signaling pathways has also been extensively studied as a way of directing rational cancer therapy in chemotherapyresistant cancers.…”

“…VEGF expression is observed in 50-80% of GBC and correlate swith metastasis disease and poor prognosis [131][132][133][134]. Tian et al investigated the involvement of the p53 gene in regulating tumor angiogenesis and observed that abnormal p53 accumulation was closely associated with a progressive increase of VEGF expression.…”