Assessment of proliferative activity in leukaemic bone marrow using the monoclonal antibody Ki-67.

Abstract

Aims-To investigate proliferative activity in leukaemic and lymphomatous bone marrow infiltrates and to assess the feasibility of transport of specimens among institutions.Methods-Proliferative activity in bone marrow trephine cryosections from 99 patients with non-Hodgkin's lymphoma (NHL), 23 patients with acute myeloid leukaemia (AML), 11 with acute lymphoblastic leukaemia (ALL), and two with acute undifferentiated leukaemia (AUL) was investigated. Infiltration was seen in 52 out of 99 cases of NHL on bone marrow cryosections. A score was devised to assess pathological infiltrates in bone marrow trephine cryosections using the monoclonal antibody Ki-67. This method of scoring gave a measure of non-erythroid proliferative activity. Results-Mean Ki-67 positivity in bone marrow infiltrates in 31 low grade B cell lymphomas (Kiel classification) was 0*3% before and 4-7% after treatment, 16'4% in seven high grade B cell lymphomas, and 17-8% in 12 peripheral T cell lymphomas. In 48 cases of NHL, bone marrow cryosections had not been infiltrated, and in all but one case the percentage of Ki-67 positive cells in normal marrow was less than 3%; the remaining case showed coexistent myelodysplasia and 8% bone marrow Ki-67 positivity. In eight cases of common ALL at diagnosis, the mean Ki-67 positivity in marrow cryosections was 24-9%, significantly higher than the 2-4% Ki-67 positivity seen in AML (p < 0.05).One of the two cases of common ALL with less than 1% Ki-67 positivity was refractory to treatment. Conclusions-Proliferative activity of erythroid elements in the bone marrow varies greatly. Immunostaining of bone marrow cryosections using permits accurate assessment of non-erythroid proliferative activity in lymphomas and leukaemia. High grade B cell lymphomas and peripheral T cell lymphomas invading the marrow have very similar mean proliferative activities. Such levels of proliferation are of the same order as those seen in common ALL, but much higher than those seen in AML. (7 Clin Pathol 1994;47:209-213) Proliferative activity in marrow can predict remission and length of remission in acute leukaemia, yet no data on the proliferation rate in trephine biopsy specimens are being collected on patients entering current trials.'2 Proliferation in lymph nodes also seems to be of prognostic value in non-Hodgkin's lymphoma (NHL).3 Many techniques for assessing proliferation exist: these include tritiated thymidine autoradiography, flow cytofluorimetry to determine the 2n-4n cell percentage, and bromodeoxyuridine (BrdU) preincubation with anti-BrdU staining and transferrin receptor analysis. Tritiated thymidine use involves lengthy cell incubation and the use of radioisotopes; the BrdU method also involves incubation of cell suspensions and, like thymidine methods, may overestimate proliferating cells caused by non-S phase DNA synthesis and repair.4Ki-67 is a monoclonal antibody which labels a proliferation associated antigen present in the nuclei of stimulated peripheral blood lymphocytes in S, G, M, and late...

Expression of the proliferation-associated nuclear protein MIB-1 and its relationship with microvascular density in bone marrow biopsies of patients with myelodysplastic syndromes

“…This time-consuming technique, which also requires isolated viable cells, has been replaced by various immunohistochemical methods that assess the proliferation rate of malignant cells (Pellegrini et al 1995). MIB-1 (which is identical to Ki-67) is a monoclonal antibody which labels a proliferation associated antigen present in the nuclei of proliferating cells in the S, G 2 , M and late G 1 phases of the cell cycle, but not in the G 0 and early G 1 phases (Gerdes et al 1984, White et al 1994. MIB-1 is a significant method for estimating the growth fraction in malignant disease and has been shown to correlate with the histopathological grade of various malignancies (Brown & Gatter 1990, Kubbutat et al 1994.…”

FragViz: visualization of fragmented networks

“…Excessive cell proliferation is a characteristic of all leukemic cells. However, previous studies [ 36 , 37 ] have shown that the proliferative index of ALL cells is significantly higher compared to AML cells.…”

Regeneração da função gonadal após reimplante de tecido ovariano vitrificado pelo Sistema >i<Ovarian Tissue Cryosystem>/i< (OTC) e outros dois protocolos na espécie murina

“…O Ki-67 é um marcador localizado no núcleo celular e é bastante utilizado para identificar células em proliferação celular, sendo este um anticorpo monoclonal (WHITE, SMITH, SMITH, 1994).…”