Significance of cell proliferation index in assessing histological prognostic categories in Hodgkin's disease. An immunohistochemical study with Ki67 and MIB-1 monoclonal antibodies.

BACKGROUND AND OBJECTIVE In their review of the Rye histopathological classification of Hodgkin's disease, Bennett and coworkers have proposed that the nodular sclerosis (NS) type should be divided into two diagnostic categories on the basis of their clinical behaviour. In order to evaluate whether the proliferative activity of HD cells might correlate with histology in NS subtypes, we reviewed and re-evaluated cryostat and paraffin-embedded sections from 80 cases sent to our centre from 1986 to 1991. METHODS In the present study, we investigated the growth cell fraction of 53 cases of Hodgkin's disease with nodular sclerosis by using Ki67 and MIB1 monoclonal antibodies to determine whether proliferative activity is associated with different pathological subtypes and prognostic categories. Eight cases with an interfollicular pattern and 19 with mixed cellularity were also investigated. The results in each group were compared to the others. RESULTS The values of Ki67 and MIB1 were highly correlated (r = 0.88). In Hodgkin's disease with nodular sclerosis, two groups with significantly different growth fractions were morphologically identified: one with lymphocyte predominance and mixed cellularity subtypes, another composed of cases with variously extensive lymphocyte depletion. The figures were compared with those of interfollicular subtype, which fell into the first group, and of mixed cellularity type, in which the proliferative cell activity was significantly higher than in the second nodular sclerosis group. In all cases, Reed-Sternberg and Hodgkin cells accounted for the majority of the cell growth fraction, although a variable percentage of T-lymphocytes were also Ki67- or MIB1-positive. Taking the median value (15%) of MIB1 positive cells as a cut-off, a significant correlation (p = 0.05) was observed between MIB1 positivity and bulky disease, and a good trend (but not a significant relationship) between MIB1 and overall survival, disease-free survival, staging and the clinical response to therapy. INTERPRETATION AND CONCLUSIONS Assessment of the growth cell fraction in Hodgkin's disease with different nodular sclerosis patterns provides biological support for the morphological reclassification of their degree of malignancy into two main groups with different impacts on the clinical parameters and a possible relation with the outcome of treatment.