Ki-67

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 the 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.

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.

Visualization

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.

Assessments

Run 5 2002

Run 19 2007

Selected references

Bryant RJ, Banks PM,O'Malley D P. Ki67 staining pattern as a diagnostic tool in the evaluation of lymphoproliferative disorders. Histopathology 2006; 48:505-15

Hall, P.A., Richards, M.A., Gregory, W.M., d'Ardenne, A.J., Lister, T.A. and Stansfeld, A.G. The prognostic value of Ki67 immunostaining in non-Hodgkin's lymphoma. J Pathol 1988;154:223-35.
Zuber, P., Hamou, M.F. and de Tribolet, N. Identification of proliferating cells in human gliomas using the monoclonal antibody Ki-67. Neurosurgery 1988;22:364-8.

Jalava P, Kuopio T, Juntti-Patinen L, Kotkansalo T, Kronqvist P, Collan Y. Ki67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification: proliferation subgroups formed based on Ki67 immunoreactivity and standardized mitotic index. Histopathology. 2006 May;48(6):674-82.

Li H, Shen H, Xu Q, Deng D, Wang S, Lu Y, Ma D. Expression of Pin1 and Ki67 in cervical cancer and their significance. J Huazhong Univ Sci Technolog Med Sci. 2006;26(1):120-2.

Lindboe, C.F. and Torp, S.H. Comparison of Ki-67 equivalent antibodies. J Clin Pathol 2002;55:467-71.

Lorinc E, Jakobsson B, Landberg G, Veress B. Ki67 and p53 immunohistochemistry reduces interobserver variation in assessment of Barrett's oesophagus. Histopathology. 2005 Jun;46(6):642-8.

Maounis NF, Chorti M, Apostolakis E, Ellina E, Blana A, Aggelidou M, Dritsas I, Markidou S. Prognostic impact of Deoxyribonucleic acid (DNA) image analysis cytometry and immunohistochemical expression of Ki67 in surgically resected non-small cell lung cancers. Cancer Detect Prev. 2006;30(6):507-14.

Mirza S, Jeannon JP, Soames J, Wilson JA. Is Ki67 a marker for the transformation of laryngeal dysplasia to carcinoma? Acta Otolaryngol. 2006 Apr;126(4):418-21.

Qi ZL, Huo X, Xu XJ, Zhang B, Du MG, Yang HW, Zheng LK, Li J, Shen ZY. Relationship between HPV16/18 E6 and 53, 21WAF1, MDM2, Ki67 and cyclin D1 expression in esophageal squamous cell carcinoma: comparative study by using tissue microarray technology. Exp Oncol. 2006 Sep;28(3):235-40.

Torp, S.H. Proliferative activity in human glioblastomas: evaluation of different Ki67 equivalent antibodies. Mol Pathol 1997;50:198-200.

Ueda, T., Aozasa, K., Tsujimoto, M., Ohsawa, M., Uchida, A., Aoki, Y., Ono, K. and Matsumoto, K. Prognostic significance of Ki-67 reactivity in soft tissue sarcomas. Cancer 1989;63:1607-11.

Veronese, S.M., Gambacorta, M., Gottardi, O., Scanzi, F., Ferrari, M. and Lampertico, P. Proliferation index as a prognostic marker in breast cancer. Cancer 1993;71:3926-31.

Walts AE, Lechago J, Bose S. P16 and Ki67 immunostaining is a useful adjunct in the assessment of biopsies
for HPV-associated anal intraepithelial neoplasia. Am J Surg Pathol. 2006 Jul;30(7):795-801.

Wang SA, Wang L, Hochberg EP, et al. Low histologic grade follicular lymphoma with high proliferation index: morphologic and clinical features. Am J Surg Pathol 2005; 29:1490-6