227P - Prognosis of phosphorylated-insulin growth factor receptor (p-IGF-1R) and metalloproteinase-3 (MMP3) expression in advanced gastrointestinal stroma...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Translational Research
Presenter Joan Maurel
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors J. Maurel1, A. Lopez Pousa2, S. Calabuig3, S. Bagué2, X. Garcia Del Muro4, X. Sanjuan4, J. Rubio5, M. Cuatrecasas1, J. Martinez-Trufero6, C. Horndler6, J. Fra7, C. Valverde Morales8, A. Redondo9, A.M. Poveda10, I. Sevilla11, N. Lainez12, M. Rubini13, X. García Albéniz14, J. Martin Broto15, E. De Álava16
  • 1Oncology, Hospital Clínic i Provincial de Barcelona, 08036 - Barcelona/ES
  • 2Medical Oncology, l'Hospital de Sant Pau i de la Santa Creu, Barcelona/ES
  • 3Oncology, Hospital General de Valencia, Valencia/ES
  • 4Oncology, ICO Hospitalet, Barcelona/ES
  • 5Oncology, ICO Girona, Girona/ES
  • 6Oncology, Hospital Miguel Servet, Zaragoza/ES
  • 7Oncology, Hospital Rio Hortega, Valladolid/ES
  • 8Oncologia Médica, Vall d'Hebron University HospitalInstitut d'Oncologia, ES-08035 - Barcelona/ES
  • 9Medical Oncology, Hospital Universitario la Paz, Madrid/ES
  • 10-, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 11Medical Oncology, C U Virgen de la Victoria, málaga/ES
  • 12Medical Oncology, Complejo Hospitalario de Navarra, Pamplona/ES
  • 13Oncology, Università degli studi di Ferrara, Ferrara/IT
  • 14Oncology, Harvard School of Public Health, Boston/US
  • 15Medical Oncology, Hospital Universitario Son Espases, ES-07010 - Palma de Mallorca/ES
  • 16Oncology, Hospital Virgen del Rocío, Sevilla/ES



Most GISTs have mutations in KIT or PDGFRA. Patients with advanced GIST with KIT exon 9, with PDGFRA mutation or WT for KIT and PDGFRA have a worse progression-free survival (PFS) compared to patients with KIT exon 11 mutated tumors. We evaluated expression of p-IGF-1R (Y1316) and MMP3 as predictors of PFS or overall survival (OS)


Ninety-six advanced GIST patients included in GEIS-16 study with KIT and PDGFRA mutational information were examined for p-IGF-1R (Y1316) and MMP3 expression in a tissue micro-array. To study activation of the IGF-1R system, we have used an antibody (anti-pY1316) that specifically recognizes the phosphorylated (active) form of the IGF-1R. DNA was extracted from paraffin-embedded tissues and intronic PCR primers were used to amplify exons 9,11,13 and 17 of KIT, 12 and 18 of PDGFRA. Bidirecctional sequencing with specific primers was performed on a ABI3100 sequencer using the Big Dye Terminator v3.1 kit. Multivariate model was built using a stepwise automated variable selection approach with criterion to enter the variable in the model of p < 0.10 and criterion to keep the variable in the model of p < 0.05. PFS was computed as the date of imatinib initiation to progression or death. Overall survival was defined as the time from imatinib initiation to death.


MMP3 was overexpressed in 10% of cases and p-IGF-1R in only 2% of cases. 68% of patients had KIT mutations, 4% had PDGFRA mutations and 28% were WT for KIT and PDGFRA. At univariate analysis KIT exon 11/13 vs rest (WT/WT, KIT exon 9 mutations and PDGFRA mutations) had better PFS (p = 0.038; HR: 0.58; 95%CI (0.35-0.96). Less than 24 months disease free-interval (HR 24.2, 95% CI 10.5-55.8), poor performance status (PS) (HR 6.3, 95% CI 2.5-15.9), extension of disease; > 1 organ (HR 1.89; 95% CI 1.03-3.4) and positive expression of p-IGF-1R or MMP3 (HR 2.1; 95% CI 1.01-4,2) but not mutational analysis (HR 1.02; 95%CI 0.53-1.96) were the strongest prognostic factors for PFS in the multivariate analysis. For OS only PS, disease free-interval and number of metastatic sites remain significant.


Our findings suggest that p-IGF-1R (Y1316) and MMP3 expression have major prognostic significance for PFS in advanced GIST treated with imatinib therapy.


All authors have declared no conflicts of interest.