The Ki67 immunohistochemistry (IHC) test is a diagnostic tool often encountered in medical discussions, particularly concerning cancer. This test provides valuable information by measuring a specific protein within cells. This article explores the biological basis of Ki67, how it is measured, how to interpret its score, and its influence on treatment decisions.
What is Ki67?
Ki67 is a protein found inside the nucleus of cells, and its presence is closely linked to cell division. It is expressed during all active phases of the cell cycle, including G1, S, G2, and M phases, but is absent when cells are in the resting G0 phase. This characteristic makes Ki67 a marker for cellular proliferation, indicating when cells are actively growing and dividing.
The protein’s expression levels are regulated by processes like transcription and protein degradation, which explains why its presence changes throughout the cell cycle. While Ki67 has long been considered a direct requirement for cell proliferation, recent genetic studies suggest it may not be strictly necessary for most eukaryotic cell division. Its significance in cancer lies in its association with rapidly dividing cells, which are a hallmark of many tumors.
How Ki67 is Measured: Immunohistochemistry
Ki67 levels in tissue samples are measured using immunohistochemistry (IHC). This method relies on antibody-antigen binding to visualize specific proteins within cells.
A tissue sample, often obtained from a biopsy, is prepared and exposed to antibodies that bind to the Ki67 protein. When these antibodies attach, a chemical reaction produces a visible stain within the cells.
Pathologists examine the stained tissue under a microscope, counting the number of cells that show Ki67 staining. This count, expressed as a percentage of the total tumor cells, is the Ki67 “index” or “score.” IHC is a widely used and routine technique in pathology laboratories for assessing various cellular markers.
Understanding Your Ki67 Score
The Ki67 score is usually presented as a percentage, representing the proportion of tumor cells actively dividing. A higher percentage indicates that a larger number of cells are proliferating rapidly, which can suggest a more aggressive tumor with faster growth. Conversely, a lower Ki67 score suggests slower cell growth and a less aggressive tumor.
For instance, a Ki67 score below 10% might be considered low, while a score above 20% or 30% is often considered high. However, there is no single universally accepted cutoff for defining a high Ki67 index, and the interpretation can vary depending on the specific type of cancer and other clinical factors. Pathologists typically count between 500 and 1000 cells to determine this percentage, focusing on nuclear staining.
Ki67 and Treatment Decisions
The Ki67 score provides valuable information that doctors integrate with other diagnostic details, such as tumor grade and stage, to determine a patient’s prognosis and guide treatment choices. A high Ki67 score, indicating rapid cell proliferation, is associated with a higher risk of recurrence and a poorer outcome in some cancers. This information helps predict how a tumor might behave and its likely response to different therapies.
In breast cancer, for example, Ki67 is used to estimate prognosis in early-stage disease to help decide if adjuvant chemotherapy is needed. The International Ki67 in Breast Cancer Working Group suggests that Ki67 scores of 5% or less, or 30% or more, can be used for clinical decision-making, particularly in estrogen receptor-positive and HER2-negative patients. For neuroendocrine tumors, the Ki67 index is a key grading parameter in the World Health Organization (WHO) classification, with higher scores (e.g., >20% for G3) indicating more aggressive disease and influencing the recommendation for platinum-based chemotherapy. While Ki67 is a significant marker, it is one piece of a larger diagnostic puzzle, and treatment decisions are always made holistically, considering the patient’s overall health and other tumor characteristics.