Proliferative activity of myeloma cells determined by Ki-67 antibody: Biological and clinical significance

Abstract

In this study we analyzed proliferative activity of myeloma cells and a possible correlation with selected clinical data, histological features and survival in 59 patients with newly diagnosed multiple myeloma (27 females and 32 males, mean age 62 years). Imunohistochemical method was applied using Ki-67 antibody on B5-fixed and paraffin-embedded bone marrow specimens to evaluate growth fraction of myeloma cells. Clinical staging was done according to the Durie-Salmon classification (4 patients had stage I disease, 16 patients stage II and 39 patients stage III). The number of Ki-67+ myeloma cells ranged from 1% to 36% (mean value 7%). In 39 of 59 patients (66.1%) number of Ki-67+ cells was less than 10% (cases with low proliferative index). Ki-67 expression significantly correlated with the clinical stage, ?2-microglobulin level, plasma cell morphology, volume of myeloma infiltration and the extent of osteolytic lesions. Patients with increased proliferative index (Ki-67+cells ?10%) showed a significantly shorter survival compared to those with low proliferative index (14 months vs. 36 months, p = 0.023). However, this difference was not shown in multivariate analysis, particularly due to the high correlation between proliferative activity and plasma cell morphology and the volume of myeloma infiltration.U ovoj studiji opisana su ispitivanja proliferativne aktivnosti mijelomskih celija i njene povezanosti sa klinicko-histoloskim parametrima i prognozom kod 59 bolesnika sa novootkrivenim multiplim mijelomom (MM). Proliferativna aktivnost odredjena je imunohistohemijskom metodom na parafinskim iseccima kostne srzi uz koriscenje Ki-67 kao primarnog antitela. Klinicki stadijum bolesti je odredjen prema Durie-Salmon klasifikaciji po kojoj je 4 bolesnika klasifikovano u prvi stadijum, 16 bolesnika u drugi i 39 bolesnika u treci klinicki stadijum. Procenat Ki-67+ mijelomskih celija se kretao u opsegu od 1 do 36% (medijana 7%). Kod 39 od 59 bolesnika (66,1%) procenat Ki-67+ celija je bio manji od 10% (mijelom sa tzv. niskim proliferativnim indeksom). Proliferativna aktivnost je bila u statisticki znacajnoj poveznosti sa klinickim stadijumom, serumskim vrednostima ?2-mikroglobulina, morfologijom mijelomskih celija, stepenom infiltracije kostne srzi i prosirenoscu osteolitickih lezija. Bolesnici sa povecanom proliferativnom aktivnoscu (Ki-67+ celija ? 10%) su imali znacajno krace prezivljavanje nego oni sa niskom proliferativnom aktivnoscu (14 meseci naspram 36 meseci, p = 0,023). Medjutim, proliferativna aktivnost se nije pokazala kao prognosticki nezavisan parametar u multivarijantnoj analizi, sto je protumaceno visoko znacajnom povezanoscu morfologije mijelomskih celija i stepena infiltracije kostne srzi sa jedne strane i proliferativne aktivnosti sa druge strane.