title: 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.
authors.affiliation: *Molecular Pathology Laboratory, Department of Pathology, School of Medicine, Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco †Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Letelier
authors.forename: Patricia
authors.initials: P
authors.lastname: Garcia
authors.forename: Pamela
authors.initials: P
authors.lastname: Leal
authors.forename: Carmen
authors.initials: C
authors.lastname: Ili
authors.forename: Kurt
authors.initials: K
authors.lastname: Buchegger
authors.forename: Ismael
authors.initials: I
authors.lastname: Riquelme
authors.forename: Alejandra
authors.initials: A
authors.lastname: Sandoval
authors.forename: Oscar
authors.initials: O
authors.lastname: Tapia
authors.forename: Juan C
authors.initials: JC
authors.lastname: Roa
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002764:Cholecystitis / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D012189:Retrospective Studies; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A