The Ki-67 protein is a nuclear protein doublet, 345-395 kDa, playing a pivotal role in maintaining cell proliferation. Ki-67 is present in all non-G0 phases of the cell cycle. Beginning in the mid G1, the level increases through S and G2 to reach a peak in M. In the end of M, is is rapidly catabolized.
The Ki-67 labelling index (LI), i.e., the percentage of cells in a tissue staining for Ki-67, indicates the growth fraction.
many tumours, the rate of cell proliferation as assessed by
Ki-67 immunoreactivity correlates with tumour grade and clinical
course. In Non-Hodgkin lymphoma a labelling index of less than
20% is seen in low grade lymphomas, greater than 20% is
associated with high grade lymphomas. Low grade lymphomas with a
labelling index in excess of 5% have a worse prognosis than
those with an index of less than 5%. In
Burkitt and Burkitt-like lymphoma,
nearly 100% of the nuclei are stained. This can be used as a
diagnostic criterion. In gliomas the indices ranges from 0% to
5% for low grade astrocytomas while anaplastic astrocytomas and
glioblastomas most frequently show an index above 10%. In soft
tissue sarcomas Ki-67 index is positively correlated with
mitotic count, cellularity and histological grade. In some benign tumours, like meningioma, a high LI is associated with a high recurrence
rate. In dysplasia in Barrett's
and in granulosa cell
tumours and ovarian serous tumours, Ki-67 LI is associated
with progression. In the former, reproducibility of dysplasia
grading is improved when Ki67 is included.
Ki-67 is used as a prognostic marker in the neoplasms mentioned above. In malignant lymphomas Ki-67 may be used to identify blast transformation. In glial tumours, the Ki-67 LI may be an aid in the differentiation between benign (LI generally < 10) and malignant (LI generally > 10) lesions.
mAbs K-2, MIB1, and MM1, and rmAb clones 30-9 and SP6 have all shown to give optimal results. Efficient HIER is important for an optimal result.
Control: Tonsil is appropriate: Almost all germinal centre cells must be very strongly stained.
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P16 and Ki67 immunostaining is a useful adjunct in the assessment of
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