Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Group for Sarcoma Research (GEIS) Study.
BACKGROUND
To assess whether deletions involving codons 557 and/or 558 (critical deletions) of exon 11 of KIT are relevant in the prognosis of relapse-free survival (RFS) in gastrointestinal stromal tumor (GIST) patients with a long follow-up.


METHODS
A univariate and multivariate analysis for RFS were carried out on 162 localized GIST patients over the entire follow-up period and over the intervals 0-4 years and >4 years. Factors assessed among others were Fletcher/National Institutes of Health and Miettinen-Lasota/Armed Forces Institute of Pathology (M-L/AFIP) risk categories, critical deletions and non-deletion-type mutation (NDTM) within exon 11 of KIT.


RESULTS
Multivariate analyses revealed that M-L/AFIP [relative risk (RR) 11.45, confidence interval (CI) 4.40-29.76, for the high-risk subgroup and RR 5.97, CI 2.09-17.06, for the intermediate subgroup] and critical deletions (RR 3.05, CI 1.59-5.85) were independent prognostic factors for RFS for the first 4 years and for the entire follow-up period. Beyond 4 years, the high-risk M-L/AFIP subgroup (RR 8.12, CI 1.48-44.4) and NDTM (RR 6.42, CI 1.17-35.12) were independent prognostic factors for RFS. The median follow-up was 84 months.


CONCLUSIONS
Critical deletions represent a time-dependent prognostic factor limited to the first 4 years after surgery, which could help identify a subset with higher and earlier risk for relapse in GIST patients.
Martin-Broto
J
J
Departments of Oncology and Hematology, Medical and Translational Hemato-Oncology Group, Hospital Universitario Son Dureta, Palma de Mallorca. Electronic address: javier.martin@ssib.es.
Gutierrez
A
A
Departments of Oncology and Hematology, Medical and Translational Hemato-Oncology Group, Hospital Universitario Son Dureta, Palma de Mallorca.
Garcia-Del-Muro
X
X
Department of Oncology, Institut Català d'Oncologia, Barcelona.
Lopez-Guerrero
J A
JA
Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia.
Martinez-Trufero
J
J
Department of Oncology, Hospital Miguel Servet, Zaragoza.
de Sande
L M
LM
Department of Oncology, Complejo Hospitalario de León, Leon.
Lainez
N
N
Department of Oncology, Hospital Virgen del Camino, Pamplona.
Maurel
J
J
Department of Oncology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica de Enfermedades Hepáticas y Digestivas, Barcelona.
De Juan
A
A
Oncology Department, Hospital de Valdecilla, Santander.
Losa
F
F
Department of Oncology, Hospital General, Hospitalet de Llobregat.
Andres
R
R
Department of Oncology, Hospital Clínico Lozano Blesa, Zaragoza.
Casado
A
A
Department of Oncology, Hospital Universitario San Carlos, Madrid.
Tejido
P G
PG
Department of Oncology, Hospital San Pedro, Logroño.
Blanco
R
R
Department of Oncology, Hospital Mutua de Terrassa, Terrassa.
Carles
J
J
Department of Oncology, Hospital del Mar, Barcelona.
Bellmunt
J
J
Department of Oncology, Hospital Vall d'Hebron, Barcelona.
Gomez-España
A
A
Department of Oncology, Hospital Reina Sofia, Córdoba.
Ramos
R
R
Department of Pathology, Hospital Universitario Son Dureta, Palma de Mallorca.
Martinez-Serra
J
J
Laboratory of Molecular Biology, Hospital Universitario Son Dureta, Palma de Mallorca.
Llombart-Bosch
A
A
Department of Pathology, Universidad de Valencia, Valencia.
Poveda
A
A
Department of Oncology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D003062:Codon; D019009:Proto-Oncogene Proteins c-kit