Role of vascular endothelial growth factor (VEGF) and VEGF-R genotyping in guiding the metastatic process in pT4a resected gastric cancer patients.
In radically resected gastric cancer the possibility to predict the site of relapse could be clinically relevant for the selection of post-surgical management. We previously showed that specific tumour integrins genotypes are independently associated with either peritoneal or hematogenous metastases (ITGA and ITGV). Recently VEGF and VEGF-R polymorphisms have been demonstrated to potentially affect tumour angiogenesis and the metastatic process in gastric cancer. We then investigated the role of VEGFs and VEGF-R genotyping in determining either peritoneal carcinosis or hematogenous metastases in radically resected gastric cancer patients. Tumour genotyping for integrins (ITGA and ITGV) was also performed according to our previous findings. Genotyping for VEGF-A, VEGF-C, VEGFR-1,2,3 and ITGA and ITGV was carried out on pT4a radically resected gastric tumours recurring with either peritoneal-only carcinosis or hematogenous metastases. 101 patients fulfilled the inclusion criteria: 57 with peritoneal carcinomatosis only and 44 with hematogenous spread only. At multivariate analysis, intestinal histology and the AC genotype of rs699947 (VEGFA) showed to independently correlate with hematogenous metastases (p = 0.0008 and 0.008 respectively), whereas diffuse histology and the AA genotype of rs2269772 (ITGA) independently correlated with peritoneal-only diffusion (p = <0.0001 and 0.03 respectively). Our results seem to indicate that combining information from genotyping of rs699947 (VEGFA, AC), rs2269772 (ITGA, AA) and tumour histology could allow clinicians to individuate gastric cancer at high risk for recurrence either with peritoneal or hematogenous metastases. The selection tool deriving from this analysis may allow an optimal use of the available treatment strategies in these patients.
Clinica di Oncologia Medica, AO Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy.
Mario
M
Scartozzi
Cristian
C
Loretelli
Eva
E
Galizia
Alessandra
A
Mandolesi
Mirco
M
Pistelli
Alessandro
A
Bittoni
Riccardo
R
Giampieri
Luca
L
Faloppi
Maristella
M
Bianconi
Michela
M
Del Prete
Francesca
F
Bianchi
Laura
L
Belvederesi
Italo
I
Bearzi
Stefano
S
Cascinu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D005260:Female; D015870:Gene Expression; D060005:Genotyping Techniques; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D013274:Stomach Neoplasms / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D039001:Integrin alpha Chains; D020033:Protein Isoforms; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor