Identification of a 3-gene model as a powerful diagnostic tool for the recognition of ALK-negative anaplastic large-cell lymphoma

Blood. 2012 Aug 9;120(6):1274-81. doi: 10.1182/blood-2012-01-405555. Epub 2012 Jun 27.

Abstract

Anaplastic large-cell lymphomas (ALCLs) are a group of clinically and biologically heterogeneous diseases including the ALK(+) and ALK(-) systemic forms. Whereas ALK(+) ALCLs are molecularly characterized and can be readily diagnosed, specific immunophenotypic or genetic features to define ALK(-) ALCL are missing, and their distinction from other T-cell non-Hodgkin lymphomas (T-NHLs) remains controversial. In the present study, we undertook a transcriptional profiling meta-analysis of 309 cases, including ALCL and other primary T-NHL samples. Pathway discovery and prediction analyses defined a minimum set of genes capable of recognizing ALK(-) ALCL. Application of quantitative RT-PCR in independent datasets from cryopreserved and formalin-fixed paraffin-embedded samples validated a 3-gene model (TNFRSF8, BATF3, and TMOD1) able to successfully separate ALK(-) ALCL from peripheral T-cell lymphoma not otherwise specified, with overall accuracy near 97%. In conclusion, our data justify the possibility of translating quantitative RT-PCR protocols to routine clinical settings as a new approach to objectively dissect T-NHL and to select more appropriate therapeutic protocols.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Anaplastic Lymphoma Kinase
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / isolation & purification
  • Biomarkers, Tumor / physiology
  • Case-Control Studies
  • Diagnosis, Differential
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, Neoplasm* / physiology
  • Humans
  • Lymphoma, Large-Cell, Anaplastic / diagnosis*
  • Lymphoma, Large-Cell, Anaplastic / genetics*
  • Microarray Analysis
  • Models, Statistical
  • Molecular Diagnostic Techniques / methods*
  • Predictive Value of Tests
  • Prognosis
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism

Substances

  • Biomarkers, Tumor
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases