Monoclonal Antibody Ki-67 as a Marker of Proliferative Activity in Monoclonal Gammopathies

Abstract

In 16 patients with monoclonal gammopathies of undetermined significance (MGUS) and in 49 with multiple myeloma (MM, 43 untreated and 6 relapsed) we used immunocytochemistry to determine the percentages of bone marrow plasma cells (BMPC) that incorporate bromodeoxyuridine (BUDR-labeling index, BUDR-LI) in vitro and that label with the monoclonal antibody Ki-67 (which recognizes an antigen thought to identify the growth fraction of the population, Ki-67 GF). Both mean and range values were greater for Ki-67 GF than for BUDR-LI. Most patients with high Ki-67 GF also had high BUDR-LI, although a linear correlation was not found between the two parameters. MGUS has lower values than MM, and the difference was much greater for Ki-67 GF than for BUDR-LI (p < 0.005 vs. p < 0.05). Differences in Ki-67 GF but not in BUDR-LI were found between MGUS and stage I MM (p < 0.0005) and between grouped stage I and II MM and stage III MM (p < 0.025). Both Ki-67 GF and BUDR-LI were significantly (p < 0.005) greater in relapsed than in untreated MM. Determining Ki-67 GF as a proliferative parameter could be a better way of studying the kinetics of (BMPC) in MGUS and MM than determining the BUDR-LI, since a wider range of values is obtained and this allows patient groups with different clinical characteristics to be separated more easily.

Ki-67 Proliferation Index

“…3 However, it displays low values because it binds only to cells in S phase and may have normal values in patients with active MM. 4 Ki-67 consists of a nuclear protein, which is expressed during the G 1 , G 2 , S, and M phases of the cell cycle but not the G 0 , thus identifying proliferating cells. It has been used by histopathologists as a marker of proliferative activity and prognosis in various tumors 5 but generally is not applied in routine pathological analysis of MM.…”

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

“…Evaluation of proliferative potential of plasma cells in MM is an acknowledged method, although in recent clinical practice not very frequently used despite its undisputed significance in the assessment of the prognosis of the disease [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The beginning experience using the measurement of proliferative index was targeted at the prognostic evaluation of patients with active MM.…”

“…The literature dealing with the evaluation of proliferative potential of myeloma plasmocytes is mainly from the time of conventional chemotherapy [1][2][3][4][6][7][8][9][10][11][12][13][14][15]. With a more advanced knowledge of the biological properties of the malignant clone, the microenvironment of the bone marrow, and their mutual interactions, it is possible to focus the treatment approach to the interference with these modalities, and a number of previously used prognostic factors (such as the degree of anemia, immunochemical type, bone marrow involvement or some cytogenetic abnormalities and others) lose their prognostic significance [41][42][43][44][45].…”

“…One of the most respected factors is the proliferative index of myeloma plasmocytes, or the "labeling index" [1][2][3][4][5][6]. Measurement of the proliferating potential of myeloma cells has been quite an established procedure, significantly dividing patients into groups with different prognosis [2][3][4][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, most of the studies assessing the proliferation of MM plasmocytes have been from the time of the treatment with the use of conventional chemotherapeutical regimens only and of the general acceptance and validity of "classical prognostic factors".…”

The Correlation Between TP53 Expression and Ki-67 Proliferation with Bartl Malignancy Degree of Plasma Cell Neoplasm

“…(16) Girino also found no correlation in Ki-67 expression in MM cases. (32) More observation is needed to find the progression of MM cases in this study.…”