The prognostic value of international prognostic index and mib-1 immunostaininig of perphiral lympoid tissues and bone marrow in patients with high

Abstract EN

Background : cell kinetic data are important indicator of the aggressiveness of tumour and clinical response.

The Ki-67 antigen plays a pivotal role in maintaining cell proliferation and the expression of this antigen was found to be a valuable indicator for aggressive disease in a variety of neoplastic disorders.

Aim of the study : this study aimed to assess the prognostic significance of the expression of Ki-67 antigen in peripheral lymphoid tissues and bone marrow, using the monoclonal antibody MIB-1 that is applicable in formaline-fixed paraffin embedded samples in cases with high-grade non-Hodgkin's lymphomas.

Material and methods : the MIB-1 immunostaining was performed on 96 samples from 48 patients with high-grade non-Hodgkin's lymphomas.

The study was performed on tissue sections, nodal or extranodal, as well as on BM smears or BM paraffin embedded sections of same patients.

Ki-67 index was determined using image analyzer.

Results: Forty-five out of the studied 48 cases (93.8 %) were positive with a median labelling index of 20.425 % (Range, 0-58 %).

We were able to detect bone marrow involvement by detecting MIB-1 positive cells in BM samples of 29 patients who were not morphologically diagnosed to have BM infiltration.

There was a strong correlation between BM positivity for Ki-67 and Ki-67 labelling index (p < 0.001).

Twenty-eight (58.3 %) out of the studied 48 cases achieved complete remission (CR).

The median duration of CR was 35 months (range, 8-42 months) and the overall survival at 48 months was 35.4 % (median 22 months, 95 % CI, 13-31 months).

The median Ki-67 index (20.425 %) was chosen as a cut-off level for statistical analysis of the variables that influence clinical outcome.

The probability of inducing CR was associated with low and low intermediate International Prognostic Index (IPI) whereas a low growth fraction was associated, although not significant, with a trend toward a higher probability of inducing a CR.

In univariate analysis, high MIB-1 labelling index and increased IPI were associated with shorter duration of complete remission and overall survival time.

Multivariate analysis showed that an extended overall survival time was associated with low MIB-1 label-ling index and with the known clinical variables included within the IPI.

Patients with high intermediate or high IPI who expressed high Ki-67 labelling index had a worse overall survival compared with patients with low or low intermediate IPI and low Ki-67 index (p < 0.001).

BM infiltration as detected by MIB-1 was correlated in univari-ate analysis (p = 0.04), although not confirmed in multi-variate analysis, with poor survival.

Conclusion: In conclusion, the MIB-1 monoclonal antibody immunostain-ing appears to be a simple and reproducible method of determining tumour proliferative index and provides useful prognostic information in patients with high-grade NHL.

We recommend using apoptotic markers in addition for proper assessment of the impact of detecting MIB-1 positive cells in BM on disease outcome