EL CRX COMO MARCADOR MOLECULAR EN EL RETINOBLASTOMA METASTÁSICO

SAMPOR CLAUDIA; GABRI MARIANO; ALONSO CRISTINA; ANA VANESA TORBIDONI; OTTAVIANI DANIELA; JORGE ROSSI; ALONSO DANIEL; VIVIANA LAURENT; VALERIA VAZQUEZ; GARCIA DE DAVILA MARIA TERESA; CHANTADA GUILLERMO

Jornada; XXXI Jornadas Multidiciplinarias de Oncología del Instituto Roffo; 2016

IMPORTANCEDisseminated retinoblastoma is usually fatal. Identification of small amounts(minimaldissemination [MD]) of tumor cells in extraocular sites might be a tool fordesigningappropriatetreatments.OBJECTIVETo test cone-rod homeobox (CRX) transcription factor as a lineage-specificmolecularmarker for metastatic retinoblastoma and for evaluation of MD.DESIGN,SETTING, AND PARTICIPANTS In a prospective cohort design study,we evaluated CRXmessengerRNA (mRNA) by retrotranscription followed by real-time polymerase chainreaction asa diagnostic test in samples obtained from bone marrow, peripheral blood, andcerebrospinalfluid (CSF) at diagnosis, after induction chemotherapy, and during follow-up.The studywas conducted from June 30, 2008, to June 30, 2014. Seventeen retinoblastomaprimarytumors, 2 retinoblastoma cell lines, and 47 samples of bone marrow from othercancers(controls) were studied. Seventeen patients with metastatic retinoblastoma (9atdiagnosis,8 at relapse; age range: 18-41 months) were included.MAINOUTCOMES AND MEASURES Detection of CRX mRNA as a marker formetastaticretinoblastomaand MD in bone marrow and CSF and its correlation with clinical findings.RESULTSCone-rod homeobox mRNA was expressed in all tumors (relative expression levelsrange, 8.1× 10−5 to 5.6) and cell lines. In control samples, there was no amplificationof CRX;only thehousekeeping gene (GAPDH) demonstrated amplification. Bone marrowmetastaticcellsshowed expression of CRX mRNA in all 9 children presenting with metastasis atthediagnosis(relative expression levels, 6.0 × 10−5 to 0.67). After induction chemotherapy,noevidence ofMD of tumor cells was seen in any of the 8 responding children since only GAPDHshowedamplification. In the CSF of children who had ametastatic relapse, CRX mRNAdetectionwas positive in 2 patients in whom no conclusive results were reached byimmunocytologyfor disialoganglioside GD2. Minimal dissemination in the CSF was associatedwith aclinical relapse in 2 cases. No concomitant MD was evident in the bone marrowinany case.CONCLUSIONSAND RELEVANCE These data suggest that CRX mRNA is a novel marker forretinoblastomaat extraocular sites. In this study among patients with bone marrowmetastasis,there was a quick, complete, and sustained molecular response after inductionchemotherapy.In all patients with secondarymetastasis, CSF relapse occurred independentlyfrom thebone marrow, suggesting a sanctuary site.