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• W2608846045 abstract "Introduction: Chordoma is a rare tumor arising from the notochord. Its lethality is largely due to its tendency to recur. Precision medicine with molecular target therapies is emerging as a promising approach. The main goal of the present project is to identify molecular and clinical biomarkers as diagnostic, therapeutic and prognostic factors useful for the management of chordoma patients. Materials and Methods: A retrospective clinical and pathological charts review of all chordoma patients treated at our Institution in the last twelve years has been performed. Clinical data were gathered together with the investigation of histopathological tumor features. Kaplan-Meier analysis was used to determine overall survival (OS). In addition, a preliminary immunohistochemical (IHC) analysis was carried out for the following markers: Brachyury, p53, beta-catenin, filamin-A, GAB‐1, EGFR, PDGFR-beta, c-MET, C-kit, PTEN, YKL-40 and TERT. Sphyngolipidomic analysis will be performed to study the ceramide species in prospectively collected frozen specimens of chordomas and nuclei pulposi, as control group. Results: The study included the last consecutive 48 patients. The average follow-up was 42 months (range 3–139). Sixty surgical operations were performed in the initial or recurrent setting. Thirty patients received post-operative radiation therapy and three patients received post-operative chemotherapy. The mean OS and PFS after surgery was 42 and 49 months, respectively. The Kaplan-Meier analysis predicted OS rates of 70%, 60%, 49% and 49% at 3, 5, 7, 10 years, respectively. The preliminary IHC analysis has been conducted on 18 specimens (eleven primary, seven recurrent). All the classical chordoma expressed Brachyury. The analysis showed a positive trend of activation of the tyrosine-kinase receptors (PDGFR-beta, c-MET, c-Kit) and the Sonic-Hedgehog pathway (GAB-1, filamin-A and beta-catenin patterns). There was a phenotypic change in the expression of PDGFR-beta and GAB-1 between the primary tumor and its recurrence after the gold-standard treatment. Interestingly, TERT expression was significantly expressed in 95% of specimens. Conclusion: Kaplan-Meier analysis confirmed that surgical resection entity represented a statistically significant factor related to OS. In the present small cohort of specimens there was a positive expression of PDGFR-beta, showing that this pathway could potentially be targeted by TRKs inhibitors. TERT expression may play a role in enabling primary tumor replicative immortality and may explain the etiology from embryonic notochordal remnants. Our preliminary IHC data showed that the Sonic-Hedgehog could be a potential pathway involved in chordoma pathogenesis that should be further studied." @default.
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• W2608846045 date "2017-04-01" @default.
• W2608846045 modified "2023-10-17" @default.
• W2608846045 title "P03.13 Molecular and clinical bio-markers in a series of 48 consecutive skull base chordoma patients" @default.
• W2608846045 doi "https://doi.org/10.1093/neuonc/nox036.128" @default.
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