Ki67

Characteristics

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.

Neoplasms

For 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 oesophagus 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. In breast cancer, the proliferative index measured by Ki67 immunoreactivity has both prognostic and predictive value.

Application

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.

Controls

Appendix is recommendable as positive and negative tissue control. Virtually all B-cells in the dark zones of the germinal centres must show a moderate to strong nuclear staining reaction, while an at least weak to moderate staining reaction must be seen in most B-cells in the light zones.
No staining reaction must be seen in the vast majority of mantle zone B-cells.
Liver or pancreas can be used primarily as supplementary negative tissue controls in which <1% of hepatocytes and epithelial cells of the exocrine pancreatic glands should be positive (inflammatory and reactive conditions can induce an elevated Ki67 score. Leukocytes can for unexplained reasons show a weak nuclear staining reaction.    

02.07.09 - SN/MV/RR