SIGNIFICANCE OF CELL-PROLIFERATION INDEX IN ASSESSING HISTOLOGICAL PROGNOSTIC CATEGORIES IN HODGKINS-DISEASE - AN IMMUNOHISTOCHEMICAL STUDYWITH 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 propo sed that the nodular sclerosis (NS) type should be divided into two di agnostic categories on the basis of their clinical behaviour. In order to evaluate whether the proliferative activity of HD cells might corr elate with histology in NS subtypes, we reviewed and re-evaluated cryo stat and paraffin-embedded sections from 80 cases sent to our centre f rom 1986 to 1991. Methods. In the present study, we investigated the g rowth cell fraction of 53 cases of Hodgkin's disease with nodular scle rosis by using Ki67 and MIB1 monoclonal antibodies to determine whethe r proliferative activity is associated with different pathological sub types and prognostic categories. Eight cases with an interfollicular p attern and 19 with mixed cellularity were also investigated. The resul ts in each group were compared to the others. Results. The values of K i67 and MIB1 were highly correlated (r=0.88). In Hodgkin's disease wit h nodular sclerosis, two groups with significantly different growth fr actions were morphologically identified: one with lymphocyte predomina nce and mixed cellularity subtypes, another composed of cases with var iously 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 w as significantly higher than in the second nodular sclerosis group. In all cases, Reed-Sternberg and Hodgkin cells accounted for the majorit y of the cell growth fraction, although a variable percentage of-T-lym phocytes were also Ki67- or MIB1-positive. Talking the median value (1 5%) 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 overa ll survival, disease-free survival, staging and the clinical response to therapy. Interpretation and Conclusions. Assessment of the growth c ell fraction in Hodgkin's disease with different nodular sclerosis pat terns provides biological support for the morphological reclassificati on of their degree of malignancy into two main groups with different i mpacts on the clinical parameters and a possible relation with the out come of treatment. (C) 1997, Ferrata Storti Founadtion.