title: Telomere maintenance mechanisms in liposarcomas: association with histologic subtypes and disease progression.
abstract: Human cancer cells maintain telomeres by telomerase activity (TA) or by alternative lengthening of telomeres (ALT). We proposed to define the prevalence of the two telomere maintenance mechanisms (TMM), to assess their association with histology, and to compare their prognostic relevance in a series of 93 patients with liposarcoma. ALT was detected by assaying ALT-associated promyelocytic leukemia nuclear bodies and TA was assayed using the telomeric repeat amplification protocol. ALT or TA was found in 25.9% or 26.6% of 139 tested liposarcoma lesions, respectively. Three lesions were ALT+/TA+ whereas approximately 50% of lesions did not show any known TMM. TMM phenotype was consistent during disease progression. ALT was prevalent in dedifferentiated and in grade 3 liposarcomas whereas TA prevailed in most round-cell myxoid and in grade 2 liposarcomas. ALT and TA incidence was similar in primary and recurrent lesions whereas metastases were more frequently TA+ than ALT+ (59% versus 18%; P = 0.04). TMM presence negatively affected patient prognosis (P = 0.001): increased mortality was associated with positivity for TA (P = 0.038) or ALT (P < 0.0001) compared with TMM absence. ALT proved to be a stronger prognostic discriminant of increased mortality than TA even when adjusted for tumor location, grade, and histology (hazard ratio for cause-specific death, 3.58 versus 1.15). Our results indicate that ALT can support fully malignant liposarcomas and is associated with unfavorable disease outcome.
authors.affiliation: Department of Experimental Oncology and Laboratories, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Costa
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: Laura
authors.initials: L
authors.lastname: Daprai
authors.forename: Raffaella
authors.initials: R
authors.lastname: Villa
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cantù
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gronchi
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Henson
authors.forename: Roger R
authors.initials: RR
authors.lastname: Reddel
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
mesh_terms: D000328:Adult; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D006801:Humans; D008080:Liposarcoma / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D017741:Survivors; D016615:Telomere / Q000378:metabolism*
chemical_list: D015415:Biomarkers