title: Chordoma of the skull base: predictors of tumor recurrence.
abstract: OBJECTIVE
  Chordomas of the skull base are generally regarded as slow-growing tumors; however, approximately 20% of these lesions have been shown to recur as early as 1 year postsurgery. The classic pathological paradigms are poor predictors of outcome, and additional markers are needed to identify patients at risk for early tumor recurrence. In this study the authors describe such a marker.
  
  
  METHODS
  In a series of 26 patients with chordomas of the skull base, the authors investigated the relationship between the biological behavior of the tumor, which was determined according to the interval for its recurrence and volume doubling time, and several pathological and molecular features, which included the histological variant, proliferative activity, mutation of p53 protein, expression of human telomerase reverse transcriptase (hTERT) messenger (m)RNA, loss of heterozygosity (LOH), and microsatellite instability. The major finding in this study was that hTERT mRNA expression in chordoma cells identifies those tumors that exhibit unusually fast rates of growth. The expression of hTERT mRNA was frequently associated with mutation of p53 protein, indicating that telomerase dysfunction combines with abnormal p53 function to initiate the unrestrained clonal expansion of the tumor cells. In cases in which the tumor was partially removed, mutation of p53 protein and expression of hTERT mRNA predicted increased doubling time for residual tumor as well as the probability of tumor recurrence. Cell proliferation, as investigated using the Ki-67 method, was significantly related to the tumor doubling time; however, the authors found that the pattern of cell proliferation was not homogeneous throughout the chordoma tissue, and that the proliferative index might change by a factor as high as 8 among different regions of the same tumor. The LOH and microsatellite instability do not seem to affect the prognosis of skull base chordomas.
  
  
  CONCLUSIONS
  Reactivation of telomerase in chordomas is a reliable predictor of outcome. The ability to predict the biological behavior of chordomas might have immediate implications in the management of this disease in patients who undergo surgery.
authors.affiliation: Institute of Neurosurgery, Departmnet of Neurosurgery, Catholic University School of Medicine, Rome, Italy. pallini@rm.unicatt.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Pallini
authors.forename: Giulio
authors.initials: G
authors.lastname: Maira
authors.forename: Francesco
authors.initials: F
authors.lastname: Pierconti
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Falchetti
authors.forename: Ester
authors.initials: E
authors.lastname: Alvino
authors.forename: Graziella
authors.initials: G
authors.lastname: Cimino-Reale
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez
authors.forename: Ettore
authors.initials: E
authors.lastname: D'Ambrosio
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002817:Chordoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D019292:Skull Base Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019098:Telomerase / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase