2. Departments of Haematology, St James’s Hospital, Dublin 8, Ireland.
Background: MIB-1 is a useful prognostic tool in Non-Hodgkin Lymphoma (NHL); in general, a high proliferative index (PI) is associated with aggressive disease. Quantitative image analysis (QIA) of tumour biomarkers has become more widespread due to the impractical nature of manual counting and the interobserver variability associated with semi-quantitative analysis.We hypothesized that a QIA algorithm would give a more accurate PI estimate, leading to better overall survival associations in cases of NHL.
Methods: 51 MIB-1 immunohistochemical slides from NHL cases were scanned using Virtuoso image analysis software (Roche Tissue Diagnostics/Ventana), and the PI was digitally quantified using a nuclear algorithm from selected regions of interest. The diagnostic PI quantified by the pathologist was recorded from the original report and validated by both study pathologists. Medical records were reviewed and disease progression details and survival time noted.
Results: Quantification of the MIB-1 index by image analysis showed strong positive correlation with the semi-quantified value(Spearman correlation coefficient =0.78; p<0.0001). Digitally-quantified MIB- 1 proliferation indices demonstrated significance with overall survival in the lymphoma cohort (HR 1.6 (0.2-10.6); p=0.05) when compared with the semi-quantified values (HR 1.6 (0.2-10.6); p=0.6). Similarly digitally-quantified MIB-1 proliferation indices demonstrated significance with progression free survival in the lymphoma cohort (HR 2.8 (0.6-13.5); p=0.05) when compared with the semi-quantified values (HR 0.4 (0.2-1.2); p=0.1).
Conclusions: QIA is a useful, reproducible and objective method of determining the MIB-1 PI in NHL cases and consideration should be given to introducing computer based algorithms into routine clinical haematopathology practice. However, QIA validation should be assessed in a larger sample cohort before consideration is given to introducing computer-based algorithms into routine clinical pathology practice.
Keywords: lymphoma, MIB-1, proliferation index, quantitative image analysis, prognosis