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Assessment of proliferative activity in leukaemic bone marrow using the monoclonal antibody Ki-67
Insights
Ki-67 immunostaining accurately measures non-erythroid proliferative activity in bone marrow infiltrates of lymphomas and leukaemias. High-grade lymphomas and acute lymphoblastic leukaemia show significantly higher proliferation than acute myeloid leukaemia.
Area of Science:
- Hematology
- Oncology
- Immunohistochemistry
Background:
- Bone marrow infiltration is common in lymphomas and leukaemias.
- Assessing proliferative activity is crucial for diagnosis and treatment monitoring.
- Standard methods for evaluating bone marrow proliferation can be limited.
Purpose of the Study:
- To investigate proliferative activity in leukaemic and lymphomatous bone marrow infiltrates.
- To assess the utility of Ki-67 immunostaining for measuring non-erythroid proliferation.
- To evaluate the feasibility of inter-institutional specimen transport.
Main Methods:
- Bone marrow trephine cryosections from 99 non-Hodgkin's lymphoma (NHL) patients and 36 acute leukaemia patients were analyzed.
- The monoclonal antibody Ki-67 was used to assess proliferative activity.
- A scoring system was developed to quantify pathological infiltrates and non-erythroid proliferative activity.
Main Results:
- Mean Ki-67 positivity varied significantly across lymphoma subtypes, with high-grade B cell lymphomas (16.4%) and peripheral T cell lymphomas (17.8%) showing higher proliferation than low-grade B cell lymphomas (0.3% pre-treatment, 4.7% post-treatment).
- In acute leukaemias, common acute lymphoblastic leukaemia (ALL) demonstrated significantly higher mean Ki-67 positivity (24.9%) compared to acute myeloid leukaemia (AML) (2.4%).
- Normal bone marrow typically showed less than 3% Ki-67 positivity, except in cases with coexistent myelodysplasia.
Conclusions:
- Ki-67 immunostaining provides an accurate assessment of non-erythroid proliferative activity in bone marrow infiltrates of lymphomas and leukaemias.
- High-grade B cell lymphomas and peripheral T cell lymphomas invading the marrow exhibit similar high proliferative rates.
- Proliferative activity in common ALL is comparable to aggressive lymphomas but substantially higher than in AML.
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 Ki-67 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.