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

E. Frei, C. Visco, Z. Y. Xu-Monette, S. Dirnhofer, K. Dybkræ, A. Orazi, G. Bhagat, E. D. Hsi, J. H. Van Krieken, M. Ponzoni, R. S. Go, M. A. Piris, M. B. Møller, Ken H. Young, Alexander Tzankov

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12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)956-961
Number of pages6
JournalJournal of clinical pathology
Volume66
Issue number11
DOIs
StatePublished - Nov 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Frei, E., Visco, C., Xu-Monette, Z. Y., Dirnhofer, S., Dybkræ, K., Orazi, A., Bhagat, G., Hsi, E. D., Van Krieken, J. H., Ponzoni, M., Go, R. S., Piris, M. A., Møller, M. B., Young, K. H., & Tzankov, A. (2013). Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma. Journal of clinical pathology, 66(11), 956-961. https://doi.org/10.1136/jclinpath-2013-201619