Ki-67: A Nuclear Antigen Uniquely Qualified as a Marker of Cellular Proliferation

Cellular proliferation is a fundamental biological process controlled by complex regulatory networks. Careful control of these networks is necessary for normal growth and development as well as for the body’s systemic response to infection or injury. Disruption or dysregulation of the mechanisms controlling cellular proliferation may result in inappropriate proliferation, such as in the formation and growth of tumors.

Numerous molecules are involved in cell cycle regulation, and there is considerable interest in identifying an antigen that can be used as a marker to specifically identify actively proliferating cells. For such an antigen to have clinical application, two basic criteria must be met: (1), the antigen should be present in all cell types during active proliferation, and (2), the antigen should rapidly degrade once the cell enters a quiescent phase.¹ The proliferation-associated nuclear antigen Ki-67 fits the bill. The Ki-67 antigen was originally identified in 1983, and named for its city of origin (Kiel, Germany) and the number of the original clone within the 96-well plate.^2,3 The primary reason Ki-67 is so useful in clinical and research applications is that Ki-67 is expressed in all active phases of the cell cycle (G1, S, G2, mitosis), but is consistently absent in quiescent cells (G0).³ Unlike other cell-cycle associated proteins, Ki-67 is not detectable during DNA repair process, and it is also rapidly degraded, with a half-life of only 1-1.5 hours.^3,4

These features make the Ki-67 antigen an excellent marker to identify cells that are actively proliferating, both in normal and tumor cell populations. While cellular proliferation can be assessed by a number of methods, immunohistochemical staining for the Ki-67 antigen is the most commonly studied. It has become widely used in histopathology, particularly as a proliferation marker in various tumor types. High proliferation rate is a hallmark of cancer, and numerous human studies have found overexpression of Ki-67 to be associated with neoplasms ranging from breast,⁵ lung,⁶ kidney,⁷ bladder,⁸ brain,⁹ ovary,¹⁰ prostate,¹¹ and thyroid,¹² as well as in neuroendocrine tumors.¹² Beyond its use in diagnosis and prognostic determinations of varied neoplasms, Ki-67 labeling index, or the percentage of immunoreactive cell nuclei, has also been used to make treatment decisions in cases of hormone-receptive breast cancer.¹³

Ki-67 is a well characterized proliferation-associated nuclear antigen with great utility in histopathology. It can be used to identify proliferating cells in healthy tissues, but is most often used as a diagnostic tool in various cancers ranging from breast to thyroid. Bethyl currently offers polyclonal and rabbit recombinant monoclonal Ki-67 antibodies for immunohistochemistry, immunocytochemistry, western blot, and proximity ligation assay applications.