TPD52 Significance in a Large Series of Ewing's Sarcoma Family of Tumors (ESFT). Support: EuroBoNet (European Network of Excellence). Contract No. 018814.
Antonio Llombart-Bosch, Isidro Machado, Silvia Calabuig-Farinas, Jose Antonio Lopez-Guerrero, Marco Alberghini, Katia Scotlandi, Piero Picci, Jeniffer Byrne. Valencia University, Spain; IVO, Valencia, Spain; Institute Ortopedic Rizzoli (IOR), Bologna, Italy; Children´s Cancer Research, Sidney, Spain
Background: Tumor Protein D52 (TPD52) was identified in the 8q21 amplicon, and is involved in cellular transformation, proliferation and metastasis. The aim of the present study is to describe the implication of TPD52 in a large series of Ewing's sarcoma (ESFT).
Design: 324 genetically-confirmed ESFT were included in the study. Out of the 324 tumors analyzed, 272 (84%) corresponded to primary localized tumors, 22 (7%) to disseminated primary tumors, 9 (3%) to recurrences, and 21 (6%) to metastases. For the prognostic analysis, we analyzed a cohort of 217 patients with localized disease. TMA sections were immunostained with TPD52 antibody (Sidney, Australia, dilution 1:250). A correlation with the expression of additional IHC markers (pan-CK, ocludin, claudin, ZO-1, e-cadherin, desmoglein, snail, slug, AKT1,2, AKT1,2,3, GSK3β, p-GSK3β, PI3kin, and ezrin) studied previously in the same series was performed.
Results: ESFT revealed TPD52 expression in 35.5% of the tumors, this protein being more frequently expressed in atypical (21/49, 41%) compared with PNET (8/31, 24%) and conventional (41/117, 35%). Comparing TPD52 expression between localized (52/161, 31.7%) and disseminated (19/36, 52.8%) cases, we observed a significant direct association between TPD52 expression and disseminated tumors (p=0.015). The majority of cases with negative IHC results for desmoglein and ocludin failed to express TPD52 (p=0.031 and p=0.0001, respectively). Additionaly, the majority of ESFT with positive IHC result for slug, ZO-19 and ezrin revealed positive TPD52 (p=0.0001, and p=0.007 and p=0.032, respectively) In the Kaplan-Meier analysis, TPD52 immunoexpression does not represents prognostic factor for progression free survival/PFS (p=0,442) and disease specific survival/DSS (p=0,237) in ESFT.
Conclusions: TPD52 is frequently expressed in ESFT, being higher in disseminated cases than in localized tumors. The correlation of TPD52 expression with a number of epithelial markers, adhesion molecules and EMT markers in ESFT may be related with the expression of an epithelial phenotype. TPD52 IHC expression does not represent an independent prognostic factor for PFS and DSS in localized ESFT.
Category: Bone & Soft Tissue
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 9, Tuesday Morning