LIM and SH3 protein 1 (LASP1) differentiates malignant chordomas from less malignant chondrosarcomas.

PURPOSE: Chordomas are malignant tumors that develop along the neuraxis between skull-base and sacrum. Chondrosarcomas show similarities with chordomas, yet show less malignant behavior. LIM and SH3 protein 1 (LASP1) is a cytoskeletal protein known to promote the malignant behavior of tumors. LASP1 was previously identified as a possibly overexpressed protein in a chordoma proteomics experiment. In this study we compare LASP1 expression in chordoma and chondrosarcoma tissue. METHODS: Biopsies of primary tumors were collected from surgically treated chordoma (n = 6) and chondrosarcoma (n = 6) patients, flash-frozen upon collection and collectively analyzed for LASP1 RNA (real-time PCR) and protein expression (western blotting). Additionally, tissue micro array (TMA)-based immunohistochemistry was applied to an archive of 31 chordoma and 1 chondrosarcoma specimen. RESULTS: In chordoma samples, LASP1 mRNA was detected in 4/6 cases and a strong 36 kDa immunoreactive protein band was observed in 4/5 cases. In contrast, 0/6 chondrosarcoma samples showed detectable levels of LASP1 mRNA and only a weak 36 kDa band was observed in 4/5 cases. Immunohistochemical analysis showed LASP1 expression in all chordoma samples, whereas chondrosarcoma specimen did not show immunoreactivity. CONCLUSION: LASP1 is strongly expressed in the majority of chordoma cases and shows low expression in chondrosarcoma tissue. Since LASP1 is known to function as oncogene and regulate cell proliferation in other tumor types, this study implicates a role for LASP1 in chordoma biology. Further studies are warranted to improve understanding of LASP1's expression and functioning within chordoma, both in vitro and in vivo.

Genes Predicting Survival of Chordoma Patients.

BACKGROUND: A chordoma is a slow-growing, invasive neoplasm in the neuraxis that is thought to arise from notochordal cells. At 10-year follow-up, the average survival rate is 50%, though individual prognosis varies substantially. We aimed to provide a comprehensive overview of the genes and proteins expressed in these tumors and their prognostic value to facilitate prognostication for patients with chordoma. METHODS: A systematic search of clinical studies that investigated expressed factors related to chordoma survival was performed in PubMed. Data extracted included RNA and protein expression data and prognostic value (in terms of overall survival, progression-free survival, disease-free survival, and recurrence-free survival) from univariate and multivariate analyses. RESULTS: This review included 78 original studies that collectively evaluated 134 expressed factors. Of these molecular factors, 96 by univariate analysis and 32 by multivariate analysis had a predictive value for patient survival. Of the molecular factors studied in multivariate analyses, 26 factors had a negative effect while 6 had a positive effect on patient survival. CONCLUSIONS: Identification of molecular factors that are associated with survival contributes to better prognostication of patients with chordoma. Given the rarity of chordoma, often only univariate analyses can be performed. Robust multivariate analyses are scarcer but provide independently significant prognostic factors. The data presented in this review can aid in prognostication for the individual patient and facilitate the development of targeted therapies.