When patients receive pathology reports, they often encounter terms like “cellular markers.” These markers are specialized proteins detected within tissue samples that provide oncologists with important information about a disease’s characteristics. The Ki-67 score is one such marker frequently highlighted in these reports, particularly in the context of cancer. Its value helps set the stage for understanding the potential behavior of abnormal cells.
Understanding the Ki-67 Marker
The Ki-67 marker is a protein found exclusively inside the nucleus of cells that are actively preparing to divide or are currently dividing. This protein is a reliable indicator of cell proliferation (cell growth and multiplication). Ki-67 is present throughout the active phases of the cell cycle: G1, S, G2, and M (mitosis).
The protein is absent in cells that are resting (the G0, or quiescent, phase of the cell cycle). By staining for this protein, pathologists can quickly identify the fraction of cells engaged in multiplication. This makes the Ki-67 protein a direct measure of the growth fraction within a cell population.
How Ki-67 Scores Are Determined
The Ki-67 score is determined through immunohistochemistry (IHC), a laboratory technique that uses antibodies to detect the protein in a tissue sample. Pathologists prepare a thin section of tissue, usually from a biopsy, and apply a specialized antibody that binds specifically to the Ki-67 protein. The bound antibody is visualized with a color-producing reaction, causing the nuclei of the proliferating cells to become stained, typically brown.
The resulting percentage is known as the Ki-67 labeling index or proliferation index. This score is calculated by the pathologist counting the number of positively stained nuclei and dividing that number by the total number of tumor cells counted in a defined area. To ensure accuracy, experts count between 500 and 1000 cells, resulting in a final percentage that reflects the proportion of cells actively dividing when the tissue was collected.
Interpreting Ki-67 Values
The concept of a “normal range” for the Ki-67 score is context-dependent; in healthy tissue, the percentage is very low, often under 5%. In tumor pathology, the score categorizes the rate of cell multiplication, where a higher percentage indicates a more rapidly growing tumor. Tumor classification relies on dividing the Ki-67 score into low, intermediate, and high proliferation categories.
A low Ki-67 score, defined as less than 10% to 20%, suggests a slowly dividing cell population. A score of 5% or less indicates a particularly low-risk tumor. Conversely, a high Ki-67 score, often set at 30% or greater, points to a highly proliferative tumor that is multiplying quickly.
Scores that fall between the low and high cut-offs (e.g., 15% to 30%) are considered intermediate, representing a growth rate that is neither slow nor overtly fast. The specific cut-off points used to define these categories can vary between different institutions and tumor types (e.g., neuroendocrine tumors versus breast cancer). This lack of universal standardization means that interpreting a Ki-67 score, particularly in the intermediate range, requires discussion with the treating oncologist.
Clinical Significance in Treatment Planning
The Ki-67 score plays a dual role in clinical decision-making, serving as both a prognostic and a predictive marker. As a prognostic marker, the score helps estimate the likelihood of disease recurrence and the patient’s long-term outcome. Tumors with a high Ki-67 score carry a higher risk of recurrence because the cells are multiplying at a faster pace.
The score also acts as a predictive marker, helping doctors determine the potential effectiveness of different systemic treatments. A high proliferation index suggests that tumor cells are frequently passing through the cell cycle, making them highly susceptible to therapies that target rapidly dividing cells, such as chemotherapy. For tumors with high Ki-67 scores, chemotherapy is often recommended to target this rapid multiplication.
Conversely, tumors with a low Ki-67 score suggest slower growth, meaning they may be less sensitive to chemotherapy. In these cases, particularly for hormone receptor-positive cancers, less aggressive treatments like hormone therapy may be the primary focus. The Ki-67 value helps stratify a patient’s risk and guides the oncologist in selecting the most appropriate therapeutic strategy.