Immunophenotypic and genotypic characterization of progression in follicular lymphomas

Yasodha Natkunam, Robert Soslow, Andras Matolcsy, Milana Dolezal, Vivek Bhargava, Daniel M. Knowles, Roger Warnke

Research output: Contribution to journalArticle

8 Citations (Scopus)


Progression of follicular lymphomas (FLs) is often accompanied by a spectrum of histologic changes and an aggressive clinical course. Although molecular alterations have been implicated in this event, the underlying factors are largely unknown. We studied the expression of selected tumor suppressor genes (P53 and retinoblastoma [RB]), oncogenes (MYC and BCL2), and a transferrin-receptor related protein (Trump) in sequential biopsies in 16 patients. Eleven patients progressed from grade 1 or 11 FL to aggressive B-cell lymphomas with diffuse morphology, whereas 5 patients presented with diffuse aggressive lymphomas and recurred with indolent lymphomas. Immunoreactivity for P53 correlated with higher histologic grade in lymphomas progressing from indolent to aggressive; however, only 1 patient who presented with aggressive lymphoma demonstrated a P53 gene mutation. Neither P53 immunoreactivity nor genotypic alterations correlated with presentation with an aggressive histology and relapse with FL. Growth fraction, as assessed by Ki-67 staining, and Trump expression correlated with histologic grade. Immunoreactivity for RB, BCL2, and MYC was seldom associated with progression. Eight of 9 cases tested exhibited identical immunoglobulin heavy and light chain rearrangements or identical BCL2 gene rearrangements in the sequential lymphomas. We conclude that P53 and Trump protein expression and proliferation activity correlate with histologic grade, but not with recurrence or progression of FL. Our results further indicate that progression of FL to diffuse aggressive lymphomas and presentation of an aggressive B-cell lymphoma followed by FL are clonally related.

Original languageEnglish
Pages (from-to)97-104
Number of pages8
JournalApplied Immunohistochemistry and Molecular Morphology
Issue number2
Publication statusPublished - Jun 2004


  • BCL2
  • Follicular lymphoma
  • Immunohistochemistry
  • MYC
  • P53
  • Progression
  • RB
  • Transferrin receptor
  • Transformation
  • Trump

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Medical Laboratory Technology

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