SOX11 and TP53 Add Prognostic Information to MIPI in a Homogenously Treated Cohort of Mantle Cell Lymphoma--A Nordic Lymphoma Group Study

Br J Haematol. 2014 Jul;166(1):98-108. doi: 10.1111/bjh.12854. Epub 2014 Mar 29.

Abstract

Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enable stratification of the clinical diverse MCL patients into three risk groups. So far, use of the MIPI in clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining the MIPI with information on molecular markers. SOX11 was shown to significantly add prognostic information to the MIPI, but in multivariate analysis TP53 was the only significant independent molecular marker. Based on these findings, we propose that TP53 and SOX11 should routinely be assessed and that a combined TP53/MIPI score may be used to guide treatment decisions.

Keywords: lymphoid malignancies; molecular diagnostics; prognostic factors.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Child
  • Cohort Studies
  • Cyclin D1 / metabolism
  • Female
  • Humans
  • Lymphoma, Mantle-Cell / diagnosis*
  • Lymphoma, Mantle-Cell / drug therapy
  • Lymphoma, Mantle-Cell / pathology
  • Male
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Prognosis
  • SOXC Transcription Factors / metabolism*
  • Severity of Illness Index
  • Survival Analysis
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • Neoplasm Proteins
  • SOX11 protein, human
  • SOXC Transcription Factors
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cyclin D1