Survivin Expression and Prognostic Significance in Pediatric Malignant Peripheral Nerve Sheath Tumors (MPNST)

Abstract

Malignant peripheral nerve sheath tumors (MPNST) are very aggressive malignancies comprising approximately 5–10% of all soft tissue sarcomas. In this study, we focused on pediatric MPNST arising in the first 2 decades of life, as they represent one the most frequent non-rhabdomyosarcomatous soft tissue sarcomas in children. In MPNST, several genetic alterations affect the chromosomal region 17q encompassing the BIRC5/SURVIVIN gene. As cancer-specific expression of survivin has been found to be an effective marker for cancer detection and outcome prediction, we analyzed survivin expression in 35 tumor samples derived from young patients affected by sporadic and neurofibromatosis type 1-associated MPNST. Survivin mRNA and protein expression were assessed by Real-Time PCR and immunohistochemical staining, respectively, while gene amplification was analyzed by FISH. Data were correlated with the clinicopathological characteristics of patients. Survivin mRNA was overexpressed in pediatric MPNST and associated to a copy number gain of BIRC5; furthermore, increased levels of transcripts correlated with a higher FNCLCC tumor grade (grade 1 and 2 vs. 3, p = 0.0067), and with a lower survival probability (Log-rank test, p = 0.0038). Overall, these data support the concept that survivin can be regarded as a useful prognostic marker for pediatric MPNST and a promising target for therapeutic interventions.

Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma

“…It is also possible that other cell cycle regulators (e.g., p16) are inactivated in cases where bi-allelic TP53 mutations are not observed; however CDKN2A deletions were not observed in our patient, as reported in some other studies (21, 48–50). Interestingly, there was an area on chromosome 17 amplified in both the MPNST and metastatic lesion containing the BIRC5 and SOX9 genes (Fig 2), both of which have been previously found in MPNSTs (17, 40, 51, 52). While BIRC5 and SOX9 are involved in cell survival (53, 54), their role in MPNST pathogenesis remains to be defined.…”

Tumor‐infiltrating, interleukin‐33–producing effector‐memory CD8+ T cells in resected hepatocellular carcinoma prolong patient survival

“…C) . On the contrary, down‐regulated genes, like Cyclin A/Cyclin A2 , FEN1 , BIRC5/Survivin , HMMR , WDR5 , HRAS , GRK6 , DNAJA1 , H2AFZ , and SUV39H1 , are responsible for mitotic progression, cell division, proliferation, and prevention of apoptosis . Further pathway analysis identified another network of genes involved in cellular organization (Fig.…”

“…In this regard, we found that HCCIS low‐ and high‐risk HCCs differ in gene expression profiles. More specifically, in HCCIS low‐risk tumors an up‐regulation of genes important for growth, cell migration control, and formation of adherens junctions was detected, whereas genes responsible for cell division, proliferation, and prevention of apoptosis were down‐regulated . Therefore, the HCCIS can identify HCCs with immunologic and molecular differences in tumor microenvironment and biology.…”

Tanshinone IIA enhances the effects of TRAIL by downregulating survivin in human ovarian carcinoma cells

“…Thus, tumor cells are sensitive to the induction of apoptosis when survivin is downregulated. Survivin expression has been reported as a novel prognostic factor in several human malignancies (Alaggio et al 2013;Krieg et al 2013;Lv et al 2014), and its expression level is correlated with poor prognosis and shorter patient survival in EOCs (Cohen et al 2003). Recently, survivin has been considered an attractive target for anticancer therapy because it exhibits low expression in most normal cells and high expression in cancer cells (Kelly et al 2011).…”