Survivin variants, expression level and sub-cellular localization in pediatric Hodgkin lymphoma

LORENZETTI, M.; MORSNA J; COLLI S; PAOLA ANDREA CHABAY; DE MATTEO, E; PRECIADO, M. V.

Mar del Plata

Congreso; SAIC-SAI-SAFE 2016; 2016

SAIC-SAI-SAFE

Survivin, a member of the inhibitors of apoptosis family is expressed during fetal development but down regulated in adult tissues. The over expression of survivin has been described in a variety of epithelial tumors, but to a lesser extent in lymphoid malignancies such as pediatric Hodgkin lymphoma (HL). In addition to wild type survivin (svn-wt) 5 splice variants were described, where Svn-wt, Svn-DEx3 and Svn-2B are clinically relevant. Moreover, sub-cellular localization was shown to alter its function as a cell cycle modulator in carcinomas. The aim of the work was to study mRNA expression of survivin major splice variants by RT-qPCR, protein expression pattern within tumor microenvironment as well as its sub cellular localization in a series of 18 pediatric HL by imunofluorescence and correlate it with proliferation and apoptosis markers, IHQ for Ki-67 and TUNEL, respectively. Svn-wt mRNA was detected in 16/18 cases while Svn-2B and Svn-DEx3 mRNA amplified in 12/18 samples; remaining cases were negative. Survivin was expressed within the nucleus in the majority of tumor cells (68-100%, median 88%), identified by double staining with CD30, and to a lesser extent in the surrounding infiltrate (21-80%, median 61%). Moreover, survivin expression, quantified as the integrated optical density of fluorescent signal was significantly stronger in tumor cells vs infiltrating cells (p=0,0003). Ki-67 stained positive in tumor cells (50-100%, median 96%) and no TUNEL+ tumor cells were detected; however, no statistical correlation was found between any survivin variant and Ki-67 or TUNEL. In conclusion, given that survivin is over expressed in the nucleus of tumor cells but that no correlation was observed between the number of survivin+ tumor cells, or the fold change expression in mRNA of any given survivin variant and ki-67+ cells, it is plausible to suggest that survivin could act as one contributing factor to the survival of tumor cells and the pathogenesis of HL