SURVIVIN VARIANTS, EXPRESSION LEVEL AND SUB-CELLULAR LOCALIZATION IN PEDIATRIC HODGKIN LYMPHOMA

LORENZETTI, M.; MOSNA M J; COLLI S; CHABAY P; DE MATTEO E; MARIA VICTORIA PRECIADO

Mar del Plata

Congreso; Reunion Anual SAIC SAI SAFE; 2016

Survivin, a member of the inhibitors of apoptosis family isexpressed during fetal development but down regulated in adulttissues. The over expression of survivin has been described in avariety of epithelial tumors, but to a lesser extent in lymphoid malignanciessuch as pediatric Hodgkin lymphoma (HL). In addition towild type survivin (svn-wt) 5 splice variants were described, whereSvn-wt, Svn-DEx3 and Svn-2B are clinically relevant. Moreover,sub-cellular localization was shown to alter its function as a cellcycle modulator in carcinomas. The aim of the work was to studymRNA expression of survivin major splice variants by RT-qPCR,protein expression pattern within tumor microenvironment as wellas its sub cellular localization in a series of 18 pediatric HL byimunofluorescence and correlate it with proliferation and apoptosismarkers, IHQ for Ki-67 and TUNEL, respectively. Svn-wt mRNAwas detected in 16/18 cases while Svn-2B and Svn-DEx3 mRNAamplified in 12/18 samples; remaining cases were negative. Survivinwas expressed within the nucleus in the majority of tumorcells (68-100%, median 88%), identified by double staining withCD30, and to a lesser extent in the surrounding infiltrate (21-8 0%,median 61%). Moreover, survivin expression, quantified as theintegrated optical density of fluorescent signal was significantlystronger in tumor cells vs infiltrating cells (p=0,0003). Ki-67 stainedpositive in tumor cells (50-100%, median 96%) and no TUNEL+tumor cells were detected; however, no statistical correlationwas found between any survivin variant and Ki-67 or TUNEL. Inconclusion, given that survivin is over expressed in the nucleusof tumor cells but that no correlation was observed between thenumber of survivin+ tumor cells, or the fold change expression inmRNA of any given survivin variant and ki-67+ cells, it is plausibleto suggest that survivin could act as one contributing factor to thesurvival of tumor cells and the pathogenesis of HL.