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Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma.

Publication ,  Journal Article
Frei, E; Visco, C; Xu-Monette, ZY; Dirnhofer, S; Dybkær, K; Orazi, A; Bhagat, G; Hsi, ED; van Krieken, JH; Ponzoni, M; Go, RS; Piris, MA ...
Published in: J Clin Pathol
November 2013

BACKGROUND: High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab (R)-era' are lacking. METHODS: To test reproducibility and applicability of observations from the 'pre-R era' to the 'R era', we examined the prognostic role of CCNE expression by immunohistochemistry in 1579 DLBCL on tissue microarrays (TMA); 339 patients were treated by CHOP and 635 by R-CHOP. RESULTS: 1209 samples (77%) were evaluable; failures were due to missing TMA punches and fixation artefacts. Mean expression of CCNE was 13% (0-85%); applying a cut-off of >16%, 382 DLBCL (31%) were positive. CCNE did not correlate with any of the known variables (IPI, primary site, cell of origin, proliferation, and BCL2- or C-MYC rearrangements). We were able to reproduce data suggesting an IPI- and response to therapy independent, negative prognostic impact of CCNE in CHOP-treated DLBCL patients: CCNE-positive cases had a median survival of 16 months compared with 57 months in negative ones (p=0.012). In R-CHOP-treated patients the prognostic impact of CCNE was abrogated and only IPI, cell of origin and response to therapy had a prognostic significance. CONCLUSIONS: Addition of R to CHOP overcomes the negative prognostic impact of CCNE in DLBCL. Thus, R not only prolongs survival in DLBCL but also serves a cautionary note that prognostic factors should not be transferred into the 'R era' without proper scientific studies.

Duke Scholars

Published In

J Clin Pathol

DOI

EISSN

1472-4146

Publication Date

November 2013

Volume

66

Issue

11

Start / End Page

956 / 961

Location

England

Related Subject Headings

  • Vincristine
  • Treatment Outcome
  • Tissue Array Analysis
  • Rituximab
  • Reproducibility of Results
  • Prognosis
  • Prednisone
  • Pathology
  • Oncogene Proteins
  • Middle Aged
 

Citation

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Frei, E., Visco, C., Xu-Monette, Z. Y., Dirnhofer, S., Dybkær, K., Orazi, A., … Tzankov, A. (2013). Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma. J Clin Pathol, 66(11), 956–961. https://doi.org/10.1136/jclinpath-2013-201619

Published In

J Clin Pathol

DOI

EISSN

1472-4146

Publication Date

November 2013

Volume

66

Issue

11

Start / End Page

956 / 961

Location

England

Related Subject Headings

  • Vincristine
  • Treatment Outcome
  • Tissue Array Analysis
  • Rituximab
  • Reproducibility of Results
  • Prognosis
  • Prednisone
  • Pathology
  • Oncogene Proteins
  • Middle Aged