Ki-67 (protein)

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Ki-67

Counting positive versus negative nuclei with Ki-67 labeling, in this case in a neuroendocrine tumor of the small intestine. To count as positive, a nucleus should be at least half within the field of view, be large enough, and not be located in the stroma. Otherwise, even weakly positive nuclei count as positive. Immunofluorescent antibody staining against neurofilament (green) and Ki-67 (red) in a mouse embryo 12.5 days after fertilization. The proliferating cells are in the ventricular zone in the Ki-67 is a protein that in humans is encoded by the MKI67 gene. It is a cellular marker for proliferation, and it is used extensively in research and diagnostic pathology to assess the growth fraction of cells in human tumors, which can be correlated with the clinical course of cancer. The Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent in resting cells (G0), making it an excellent marker for determining the fraction of proliferating cells in a given population of cells.

Function

Ki-67 is a nuclear protein that is associated with and may be necessary for cellular proliferation. Furthermore, Ki-67 expression is correlated with cell division, being highest in the G2 and M phases of the cell cycle, while the protein is not detected in quiescent cells (G0 phase). The exact function of Ki-67 is not fully understood, but it is thought to play a critical role in maintaining cell proliferation.

Clinical Significance

In oncology and histopathology, Ki-67 is a widely used marker to assess the growth fraction of cells in tumors. A high Ki-67 index (the percentage of Ki-67-positive cells among the total number of tumor cells observed) is often associated with aggressive tumors, which have a higher probability of growth and metastasis. Assessing the Ki-67 index can help in the prognosis and treatment planning for cancer patients, as it provides information on the aggressiveness of the tumor.

Immunohistochemistry

The detection of Ki-67 protein expression is commonly performed using immunohistochemistry on tissue sections. This technique involves the use of specific antibodies that bind to the Ki-67 protein, which can then be visualized using various detection systems, allowing pathologists to determine the proportion of cells that are actively proliferating within a tumor.

Limitations and Considerations

While Ki-67 is a valuable tool in the assessment of tumor proliferation, there are some limitations and considerations to keep in mind. The interpretation of Ki-67 staining can be subjective, and there is variability in the assessment of the Ki-67 index due to differences in staining techniques, the selection of the area of the tumor to be evaluated, and the cutoff values for high and low Ki-67 expression. Therefore, the Ki-67 index should be interpreted in the context of other clinical and pathological findings.

Research Applications

Beyond its clinical applications, Ki-67 is also used in basic and translational cancer research to study cell proliferation and the effects of various treatments on tumor growth. It serves as a crucial marker in studies aiming to understand the mechanisms of cancer progression and in the development of new therapeutic strategies.