The Ki-67 score is a common finding on pathology reports used as a molecular indicator in cancer diagnosis. This score measures the proportion of tumor cells actively engaged in cell division, or proliferation. By quantifying how quickly a tumor is growing, the Ki-67 score helps medical professionals understand the potential behavior and aggressiveness of a patient’s cancer, aiding in treatment strategy determination.
The Biology of the Ki-67 Protein
The Ki-67 protein is a large nuclear protein essential for cell proliferation. The gene responsible for encoding this protein is MKI67, located on human chromosome 10. This protein is present only when a cell is actively preparing to divide or is in the process of dividing, making it a reliable marker for cellular activity.
The cell cycle consists of several phases: G0, G1, S, G2, and M. Ki-67 is reliably detected during the active phases (G1, S, G2, and M), but is entirely absent during the G0 phase, when the cell is at rest. When pathologists measure Ki-67, they are counting tumor cells that are not in the resting G0 state.
The protein functions within the cell nucleus, playing a role in chromosome organization and segregation during mitosis. It acts as a structural component that helps ensure chromosomes are properly distributed between the two new daughter cells. The presence of Ki-67 is a direct biological signal that a cell has committed to replication.
How Pathologists Calculate the Ki-67 Score
Pathologists determine the Ki-67 score using immunohistochemical (IHC) staining on a tumor tissue sample. A specific antibody is applied to the tissue section that selectively binds to the Ki-67 protein within the cell nuclei. This binding causes the nuclei of actively dividing cells to change color, usually brown, while resting cells remain the color of the counterstain.
The Ki-67 score is calculated as a percentage, representing the proportion of stained (positive) tumor cell nuclei relative to the total number counted. For instance, a score of 30% means that three out of every ten cancer cells are actively proliferating. Pathologists typically count a minimum of 500 cells across multiple high-power fields to ensure the percentage is representative.
A challenge in calculating the score is inter-observer variability between different pathologists or laboratories. To address this, current guidelines recommend counting cells in multiple areas of the tumor to capture the overall or “global” expression. This method avoids focusing only on “hot spots” and provides a more consistent result by accounting for natural variation in proliferation rates.
Interpreting Ki-67 Results and Tumor Aggressiveness
The Ki-67 score functions as a primary prognostic tool, helping predict the likely course and outcome of the disease before treatment begins. A higher Ki-67 percentage correlates with a higher rate of cell division, suggesting a more rapidly growing and aggressive tumor. Conversely, a lower score implies slower growth and a less aggressive cancer with a better long-term prognosis.
While specific thresholds vary by cancer type, general categories classify tumor aggressiveness. For many solid tumors, a score below 10% is considered low, suggesting a slow-growing tumor with a favorable prognosis. Scores between 10% and 20% indicate a moderate rate of proliferation, while scores above 20% or 30% are classified as high, signaling a fast-growing, aggressive tumor.
Tumors with high Ki-67 scores are associated with a greater risk of recurrence and a poorer overall survival rate compared to low-score tumors. The score provides a snapshot of the tumor’s velocity, allowing oncologists to gauge how urgently the cancer needs to be treated. This prognostic information is integrated with other factors, such as tumor size and lymph node involvement, to form a comprehensive risk assessment.
Ki-67’s Role in Guiding Cancer Treatment
Beyond its prognostic value, the Ki-67 score acts as a predictive tool, helping determine the most effective treatment strategy. Treatments that specifically target rapidly dividing cells, such as chemotherapy, are more likely to be effective against tumors with a high Ki-67 score. A high proliferation rate suggests the cancer cells are more vulnerable to the cytotoxic effects of these drugs.
In breast cancer, the Ki-67 score distinguishes between molecular subtypes, which dictates the treatment plan. For hormone receptor-positive tumors, a low Ki-67 score often suggests the Luminal A subtype, manageable with endocrine therapy alone. A high Ki-67 score indicates the Luminal B subtype, suggesting the patient may benefit from adding chemotherapy to the endocrine regimen.
The predictive role of Ki-67 extends to neuroendocrine tumors (NETs), where the score is fundamental to grading the disease. In high-grade NETs, specific Ki-67 cutoffs, such as 55%, are used to select chemotherapy regimens. Tumors with lower Ki-67 percentages respond differently than those with a very high percentage, which often require more intensive, platinum-based chemotherapy.