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Updated: Apr 25, 2026
Multiplexed Fluorescent Immunohistochemical Staining, Imaging, and Analysis in Histological Samples of Lymphoma
Published on: January 9, 2019
Identification of MUM1 as a prognostic immunohistochemical marker in follicular lymphoma using computerized image
Luc Xerri1, Emmanuel Bachy2, Bettina Fabiani3
1Departments of Bio-Pathology, Molecular Oncology, Hematology, and Tumor Immunology, Institut Paoli-Calmettes and Aix-Marseille Université, 13009 Marseille, France.
Abstract:
Detection of MUM1+ cells in follicular lymphoma (FL) tissues was previously found to be associated with poor prognosis in a single report, whereas the usefulness of Ki-67 immunostaining remains debated. Our goal was to establish whether these markers have predictive value for patients with FL. We analyzed MUM1 and Ki-67 expression using immunohistochemistry in biopsy samples from 434 patients from the PRIMA randomized trial. The MUM1 prognostic value was then validated in a cohort of 138 patients from the FL2000 randomized trial, using the optimal cutoff value obtained from the PRIMA cohort. The surface of positive staining was quantified using computerized image analysis. In the PRIMA cohort, both high levels of MUM1 positivity (cutoff value of 0.80%) and high levels of Ki-67 positivity (cutoff value of 10.25%) were significantly associated with a shorter progression-free survival (PFS) (P = .004 and P = .007 for MUM1 and Ki-67, respectively). In a multivariate Cox proportional hazards regression model, only MUM1 retained a statistical significance (hazards ratio 1.56; 95% confidence interval, 1.02-2.37; P = .038) after adjustment for the maintenance arm of treatment and the follicular lymphoma international prognostic index score. In the FL2000 cohort, high levels of MUM1 positivity were significantly associated to a shorter PFS (P = .004) and to a trend toward a shorter overall survival (P = .043). This remained significant using a multivariate Cox regression model after adjustment for the follicular lymphoma international prognostic index and the treatment arm for PFS (P = .016). These results show that MUM1 is a strong and robust predictive immunohistochemical marker in patients with FL.
Insights
MUM1 expression in follicular lymphoma (FL) tissues is a strong predictor of patient outcomes, indicating a shorter progression-free survival. This finding highlights MUM1 as a robust immunohistochemical marker for FL prognosis.
Area of Science:
- Oncology
- Hematology
- Immunohistochemistry
Background:
- Previous studies suggested MUM1+ cells in follicular lymphoma (FL) tissues correlate with poor prognosis, but Ki-67's predictive value is uncertain.
- The prognostic significance of these markers in FL requires further validation.
Purpose of the Study:
- To determine the predictive value of MUM1 and Ki-67 expression in patients with follicular lymphoma.
- To validate MUM1 as a prognostic marker in a separate FL cohort.
Main Methods:
- Immunohistochemistry was used to analyze MUM1 and Ki-67 expression in biopsy samples from 434 patients in the PRIMA trial and 138 patients in the FL2000 trial.
- Computerized image analysis quantified positive staining.
- Multivariate Cox regression models were employed for prognostic analysis.
Main Results:
- High MUM1 positivity (≥0.80%) and Ki-67 positivity (≥10.25%) were associated with shorter progression-free survival (PFS) in the PRIMA cohort.
- In multivariate analysis of the PRIMA cohort, only MUM1 remained statistically significant for PFS.
- High MUM1 positivity was significantly associated with shorter PFS and showed a trend toward shorter overall survival in the FL2000 cohort, confirmed by multivariate analysis.
Conclusions:
- MUM1 is a strong and robust predictive immunohistochemical marker for follicular lymphoma.
- MUM1 expression levels can aid in predicting progression-free survival and overall survival in FL patients.
