Does FDG Uptake Correlate With VEGF Family And Their Receptors Expression In Lung Adenocarcinoma?

Part 1: Microchip study:the relationship between FDG uptake and gene level expression of VEGF family and their receptorsObjectiveTo find out the relationship between FDG uptake and gene level expression of VEGF family and their receptors and get the possible candidate genes.Materials and MethodsSurgical specimen were obtained from 6 patients with lung adenocarcinoma and divided into low FDG uptake group(less than mean SUV,n=3)and high FDG uptake group(higher than mean SUV,n=3).The gene level study was achieved by Oligo DNA microarray(Human U133 plus 2.0)and analysed with GeneSpring 7.3 software.ResultsAs the conference gene,β-actin expressed stable and similar in both groups.All the VEGFs and their receptors were found after the database searching.In the gene level study,none of the VEGFs or the receptors had a significant difference between low and high FDG uptake group except VEGF-D.The gene level expression of VEGF-D of low FDG uptake group was clearly higher than that of high FDG uptake group(P= 0.0241). Conclusion1.The data of our genechip study is reliable,because the house-keeping gene,β-actin,expressed stable and similar in both groups.2.VEGF -A,B,C,PIGF and VEGFR-1,2,3 do not correlate with FDG uptake significantly in lung adenocarcinoma;3.There is a significant difference between low and high FDG uptake group for VEGF-D gene level expression:The expression of VEGF-D of low FDG uptake group was clearly higher than that of high FDG uptake group(P=0.0241).Part 2: Immunohistochemical study:the relationship between FDG uptake and the expression of VEGF-D in lung adenocarcinomaObjectiveto further confirm the relationship between FDG uptake on PET and the protein expression of VEGF-D in lung adenocarcinoma.Materials and Methods49 patients with lung adenocarcinoma were involved.Thirteen patients had bronchioloalveolar carcinoma(BAC),15 had well-differentiated adenocarcinoma,14 had moderately differentiated adenocarcinoma,and 7 had poorly differentiated adenocarcinoma.The tumor size,pathologic stage and recurrent time of each case were recorded.Anti-human VEGF-D antibody(AF286,produced by R&D company, Abingdon,United Kingdom),was applied on 5-μm paraffin-embedded sections.All the procesures were applied according to the guidance.The levels of staining were classified into four grades:-:0%of cells;±:＜10%of cells;+:10-50%of cells and ++:＞50%of cells.-,±were regarded as negative and the rest were regarded as positive.ResultsFor all the cases and for non-BAC cases,the FDG uptake was significantly higher in VEGF-D negative group(P＜0.001).For all the cases and for non-BAC cases,the expression of VEGF-D showed close correlation with lymph node metastasis(P＜0.001 for both),histological subtypes(P=0.002 for all patients and P=0.019 for non-BAC patients)and recurrence(P＜0.001 for all patients and P=0.001 for non-BAC patients).The expression of VEGF-D was always significantly higher in the group without lymph node metastasis.Using the Kaplan-Meier method,we analyzed the prognostic impact of VEGF-D in lung adenocarcinoma.47 cases were analyzed. Obviously,patients with low VEGF-D had much better disease-free survival probabilities.Conclusion1.VEGF-D expression showed a significant reverse correlation with FDG uptake (P＜0.001);2.VEGF-D showed close correlation with lymph node metastasis,histological subtypes and recurrence;3.VEGF-D can be a reverse predictor for the prognosis of lung adenocarcinoma;4.VEGF-D might be a bridge connecting the FDG uptake with the prognosis and lymphatic metastasis in lung adenocarcinoma.