Abstract 4253: A vascular endothelial growth factor gene polymorphism predicts malignant potential in intraductal papillary mucinous neoplasm
Authors: Yamada Suguru , Yabusaki Norimitsu , Fujii Tsutomu , Kanda Mitsuro , Sugimoto Hiroyuki , Kodera Yasuhiro 
Published: August 2015

Background

Intraductal papillary mucinous neoplasms (IPMNs) are well known to be premalignant lesions that sequentially progress from adenoma to carcinoma. Radiological type, size of cystic mass, and the presence of mural nodules are widely accepted as predictive malignant factors; however, its underlying mechanism is still unclear. Angiogenesis plays an important role in the progression and metastasis of various tumor types, and vascular endothelial growth factor (VEGF) is a critical component. In previous studies, at least 30 single-nucleotide polymorphisms (SNP) of the VEGF gene have been reported. VEGF +405G/C SNP (rs2010963) is located within the 5′-untranslated region and may affect transcription factor binding affinity. In contrast, VEGF -460C/T SNP (rs833061) is located in the promoter region and may influence promoter activity. Recent studies reported that serum VEGF levels were significantly higher in pancreatic ductal adenocarcinoma (PDAC) patients compared with control subjects, and VEGF +405G/C SNP was strongly associated with the carcinogenesis of PDAC patients.

Objective

The aim of this study was to investigate the distribution of VEGF SNPs with regard to malignant transformation in IPMN patients. Furthermore, correlations between VEGF SNPs and clinicopathological parameters including the morphological subtypes were statistically analyzed.

Methods

A total of 169 IPMN and 108 PDAC patients who underwent curative resection were enrolled. Low grade and moderate dysplasia were defined as benign IPMNs, on the other hand, high grade dysplasia and invasive carcinoma were defined as malignant IPMNs. The intraductal components were classified into four distinct epithelial subtypes, gastric, intestinal, pancreatobiliary, and oncocytic, based on their epithelial morphology on hematoxylin and eosin staining. VEGF +405G/C and -460C/T polymorphisms were examined by TaqMan Allele Discrimination.

Results

VEGF +405C/C was found more frequently in malignant IPMNs compared with +405G/G (odds ratio: 2.7, P = 0.04), and +405C allele was associated with malignant IPMNs compared with +405G (P = 0.055). In branch duct IPMNs, VEGF +405C/C was significantly associated with malignant transformation (CC vs GG; odds ratio: 4.0, P = 0.03, CC vs CG+GG; odds ratio: 3.3, P = 0.04), and there was a trend of VEGF +405C/C associated with malignant transformation of gastric type IPMNs (CC vs GG; odds ratio: 3.0, P = 0.07). When the survival outcomes were analyzed based on VEGF +405G/C SNPs, however, there was no relationship between VEGF SNPs and overall survival in patients with both IPMNs and PDAC.

Conclusion

VEGF +405G/C SNP was significantly associated with malignant transformation in IPMNs, especially branch duct and gastric type IPMNs. VEGF +405G/C SNP might be helpful in predicting clinical course in pancreatic disease with potential for malignant transformation.

Citation Format: Suguru Yamada, Norimitsu Yabusaki, Tsutomu Fujii, Mitsuro Kanda, Hiroyuki Sugimoto, Yasuhiro Kodera. A vascular endothelial growth factor gene polymorphism predicts malignant potential in intraductal papillary mucinous neoplasm. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4253. doi:10.1158/1538-7445.AM2015-4253