Analysis of four human PlGF isoforms and of VEGFR-1 in esophageal carcinoma.

Abstract

4160 Background: Placental growth factor (PlGF) and its receptor vascular endothelial growth factor receptor-1 (VEGFR-1) are involved in tumor progression. Humans can express four PlGF isoforms (PlGF1-4), but it is unknown, whether all of them are expressed in cancer. In this retrospective exploratory study, we analyzed expression levels of PlGF1-4 and of VEGFR-1 in primary esophageal tumor tissue and correlated gene expression data with clinical data. We included presence of disseminated tumor cells (DTCs) in the bone marrow in our analysis, which has recently evolved as adverse prognostic factor in different cancers. Methods: Gene expression levels were determined by QRT-PCR in primary tumor samples of 69 patients with esophageal cancer. Subsequently, expression data were correlated with clinical data (pT, pN, pM, DTCs). For analysis of association between expression levels and categorical clinical parameters Wilcoxon's test for independent samples was used. For correlations between quantitative variables, Kendall's tau (τ) was used to measure the degree of dependence. Results: PLGF-1, PLGF-2 and VEGFR-1 were expressed in virtually all analyzed tumor samples. Expression of PLGF-3 and PLGF-4 were limited to 59% and 74% of the analyzed patients, respectively. Expression levels of all PlGF variants were correlated amongst each other (Kendall tau rank>0.55). Expression of PlGF splice variants was not correlated with clinical variables. Interestingly, expression levels of VEGFR-1 predict presence of DTCs in bone marrow (p = 0.002). Patients with DTC in bone marrow had lower expression levels of VEGFR-1 within primary tumor tissue than patients without DTCs (0.004 ± 0.01 vs. 0.07 ± 0.15). In contrast, VEGFR-1 expression level was not correlated with lymphatic or distant macrometastasis, indicating a potential specific role of VEGFR-1 in protecting from dissemination of tumor cells into the bone marrow. Conclusions: All four known isoforms of PLGF are expressed in human esophageal cancer. Furthermore, VEGFR-1 levels are inversely correlated with presence of DTCs in the bone marrow of patients. If validated in prospective studies, VEGFR-1 expression in tumors might serve as novel prognostic biomarker for bone marrow micrometastasis. No significant financial relationships to disclose.