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

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.