Transcriptional analysis distinguishes breast implant-associated anaplastic large cell lymphoma from other peripheral T-cell lymphomas

Arianna Di Napoli, Loris De Cecco, Pier Paolo Piccaluga, Mohsen Navari, Valeria Cancila, Claudia Cippitelli, Giuseppina Pepe, Gianluca Lopez, Francesca Monardo, Antonella Bianchi, Emanuele Stefano Giovanni D'Amore, Umberto Gianelli, Fabio Facchetti, Emilio Berti, Govind Bhagat

Research output: Contribution to journalArticle

Abstract

Breast implant-associated anaplastic large cell lymphoma is a new provisional entity in the revised World Health Organization classification of lymphoid malignancies, the pathogenesis and cell of origin of which are still unknown. We performed gene expression profiling of microdissected breast implant-associated anaplastic large cell lymphoma samples and compared their transcriptional profiles with those previously obtained from normal T-cells and other peripheral T-cell lymphomas and validated expression of selected markers by immunohistochemistry. Our results indicate that most breast implant-associated anaplastic large cell lymphomas exhibit an activated CD4+ memory T-cell phenotype, which is associated with CD25 and FoxP3 expression. Gene ontology analyses revealed upregulation of genes involved in cell motility programs (e.g., CCR6, MET, HGF, CXCL14) in breast implant-associated anaplastic large cell lymphomas compared to normal CD4+ T-cells and upregulation of genes involved in myeloid cell differentiation (e.g., PPARg, JAK2, SPI-1, GAB2) and viral gene transcription (e.g., RPS10, RPL17, RPS29, RPL18A) compared to other types of peripheral T-cell lymphomas. Gene set enrichment analyses also revealed shared features between the molecular profiles of breast implant-associated anaplastic large cell lymphomas and other types of anaplastic large cell lymphomas, including downregulation of T-cell receptor signaling and STAT3 activation. Our findings provide novel insights into the biology of this rare disease and further evidence that breast implant-associated anaplastic large cell lymphoma represents a distinct peripheral T-cell lymphoma entity.

Original languageEnglish
Pages (from-to)216-230
Number of pages15
JournalModern Pathology
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 2019

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Keywords

  • Adult
  • Breast Implants/adverse effects
  • Female
  • Humans
  • Lymphoma, Large-Cell, Anaplastic/genetics
  • Lymphoma, T-Cell, Peripheral/genetics
  • Transcriptome

Cite this

Di Napoli, A., De Cecco, L., Piccaluga, P. P., Navari, M., Cancila, V., Cippitelli, C., Pepe, G., Lopez, G., Monardo, F., Bianchi, A., D'Amore, E. S. G., Gianelli, U., Facchetti, F., Berti, E., & Bhagat, G. (2019). Transcriptional analysis distinguishes breast implant-associated anaplastic large cell lymphoma from other peripheral T-cell lymphomas. Modern Pathology, 32(2), 216-230. https://doi.org/10.1038/s41379-018-0130-7