The biological and clinical significance of the KI‐67 growth fraction in multiple myeloma

Abstract

We tested the significance of the Ki-67 plasma cell growth fraction in 49 bone marrow samples from 42 patients with multiple myeloma (MM). As a new approach to study myeloma cell proliferation, strong positivity of the CD38 antigen as plasma cell related feature was simultaneously evaluated with nuclear Ki-67 expression in a flow cytometric double immunofluorescence assay. Mean Ki-67 values were significantly higher in MM at relapse (22.4 per cent +/- 10.4) as compared with MM at diagnosis (11.9 per cent +/- 8.4, p less than 0.005) and plateau-phase (10.0 per cent +/- 5.5, p less than 0.001), respectively. Serial observations in six patients confirmed this change in cell kinetic behaviour during the course of the disease. Elevated Ki-67 values correlated significantly with stage III (versus stage I, p less than 0.05), beta-2-microglobulin serum levels greater than 6 (p less than 0.001), plasmablastic morphology (p less than 0.001), and diploid myeloma cell DNA-content (p less than 0.005). No correlation was found between Ki-67 and immunoglobulin isotypes as well as immunophenotypic features (expression of CD10, CD33, and CD56) of myeloma cells. Clinically, six of seven patients with Ki-67 greater than 14 per cent at diagnosis had an unfavourable course (primary resistant disease or early relapse), and three of four patients with elevated Ki-67 values at plateau-phase relapsed within 3 months. Our results demonstrate the usefulness of Ki-67 in determining proliferative activity in MM and emphasize its value in the evaluation of the risk profile of MM patients.

APRIL promotes cell-cycle progression in primary multiple myeloma cells: influence of D-type cyclin group and translocation status

“…To study cell-cycle progression, we used a flow cytometric assay using Ki67 and PI and observed that the baseline S ϩ G 2 M fraction correlates with disease progression, confirming previous reports. 25,26 As far as we know, ours is the first demonstration of G 1 /S progression in a series of primary MM cells in response to mitogenic stimuli. We validated our results using BrdU and 3 H-thymidine incorporation, standard assays for DNA synthesis.…”

Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles

“…Unlike well-differentiated plasma cell neoplasms, plasmablastic plasma cell myelomas usually have an extremely high proliferation index and alterations in cell cycle regulators such as p16, p21, and p53. 10,[36][37][38] In situ hybridization assays for EBER were positive in all five cases of plasmablastic lymphoma analyzed, and were negative in all plasmablastic plasma cell myelomas. Although the number of cases analyzed is relatively small, the difference in EBER expression between plasmablastic lymphoma and plasma cell myeloma was highly statistically significant (Po0.002).…”

Thalidomide and bortezomib overcome the prognostic significance of proliferative index in multiple myeloma

“…In order to have comparable results we used the propidium iodide stain, which easily detects the S-phase. The Ki-67 index evaluates all the cell cycle phases [46,47] and represents rather the "cycling" potential, and it does not necessarily correspond to proliferation detected by the BrdUrd or PC-PI techniques. Other methods such as immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) [48], detection of AgNORs (argyrophillic proteins associated with the nucleolar organizer regions) in histological samples [49], cyclin D1 detection [50] and some others are not widely used in clinical practice.…”