ALT-associated promyelocytic leukaemia body (APB) detection as a reproducible tool to assess alternative lengthening of telomere stability in liposarcomas

L. Venturini, R. Erdas, A. Costa, A. Gronchi, S. Pilotti, N. Zaffaroni, M. G. Daidone

Research output: Contribution to journalArticlepeer-review

Abstract

Most cancers maintain telomeres by activating telomerase, but a significant minority, mainly of mesenchymal origin, utilize an alternative lengthening of telomeres (ALT) mechanism. We previously showed the presence of ALT, as detected by ALT-associated promyelocytic leukaemia bodies (APBs) by combined promyelocytic leukaemia immunofluorescence and telomere fluorescence-in situ hybridization, in approximately 25% of frozen specimens obtained from adult patient liposarcomas and proved that ALT negatively affects patient prognosis. In the present study, we assessed the reproducibility of APB detection on frozen versus formalin-fixed, paraffin-embedded specimens from the same liposarcoma specimens and investigated the eventual stability of ALT in 103 different lesions from 40 adult patients followed during their disease. Irrespective of liposarcoma subtype, we (1) confirmed the presence of ALT in 21.4% of tumours; (2) demonstrated the reliability of ALT-associated promyelocytic leukaemia body detection in formalin-fixed, paraffin-embedded sections (with qualitative concordance between matched frozen and formalin-fixed, paraffin-embedded samples in 29/30 specimens, and high quantitative agreement, as indicated by a Spearman correlation coefficient of 0.85); and (3) suggested the stability of ALT status during disease evolution, since the ALT mechanism was never acquired in the 29 patients with initially ALT-negative lesions and lost over time in only two of 11 patients with initially ALT-positive liposarcomas. In conclusion, these results confirm the possibility of investigating the ALT mechanism in archival specimens to obtain biologically relevant information on liposarcoma progression, even when the primary lesion is not available.

Original languageEnglish
Pages (from-to)410-414
Number of pages5
JournalJournal of Pathology
Volume214
Issue number4
DOIs
Publication statusPublished - Mar 2008

Keywords

  • ALT-associated promyelocytic leukaemia bodies (APBs) detection
  • Alternative lengthening of telomeres (ALT) mechanism
  • Archival specimens
  • Liposarcoma
  • Telomere maintenance

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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