Ki-67 is a protein discovered in human cells in the early 1980s. Found within the nucleus, it plays a role in cellular processes. Its presence serves as a general indicator in medical diagnostics, particularly when assessing cellular activity.
Understanding Ki-67’s Role
Ki-67 functions as a marker of cell proliferation, indicating how quickly cells are dividing. The protein is expressed during all active phases of the cell cycle, including G1, S, G2, and mitosis, but is absent when cells are in a resting state (G0 phase). This characteristic makes Ki-67 a useful tool for determining the growth fraction of a cell population.
Ki-67 levels are typically assessed using immunohistochemistry (IHC). This method involves staining tissue samples with an antibody that binds specifically to the Ki-67 protein, allowing pathologists to visualize and count positive cells under a microscope. The result is expressed as a percentage, representing the proportion of actively proliferating cells.
Interpreting Ki-67 Values
There is no single “normal range” for Ki-67 like a fixed number in a typical blood test. For healthy, non-cancerous tissues, the Ki-67 index is very low, often less than 3%. This indicates a low rate of cell division in normal functioning tissues.
In oncology, the interpretation of Ki-67 percentages is highly dependent on the specific type of cancer and tissue involved. For instance, in breast cancer, a Ki-67 index below 5% is considered low, while 30% or higher is considered a high proliferation rate. Some guidelines classify tumors with a Ki-67 index less than 14% as low proliferation (Luminal A-like), and those greater than 14% as high proliferation (Luminal B-like). Intermediate values, often between 10% and 20%, can be more challenging to interpret and are a subject of ongoing discussion among experts.
Clinical Significance of Ki-67
Ki-67 values are utilized by healthcare professionals to understand disease behavior and guide treatment decisions. It serves as a prognostic marker, indicating the likely course of a disease. For example, higher Ki-67 levels in certain cancers, such as breast, prostate, and neuroendocrine tumors, are associated with more aggressive tumor behavior, a higher risk of recurrence, and a less favorable prognosis.
Ki-67 also acts as a predictive marker, offering insights into the probable response to certain treatments. In breast cancer, a higher Ki-67 index can suggest a greater likelihood of response to neoadjuvant chemotherapy, administered before surgery. Conversely, low Ki-67 expression might indicate a limited benefit from certain cytotoxic chemotherapies. Clinicians consider Ki-67 alongside other factors, such as tumor grade and hormone receptor status, to develop tailored treatment strategies and assess the potential effectiveness of systemic therapies.
Factors Affecting Ki-67 Measurement and Interpretation
The assessment of Ki-67 can be influenced by several variables and presents challenges. Differences in laboratory techniques, such as tissue fixation protocols and specific antibodies used for staining, can affect the reported Ki-67 index.
Scoring methodologies also contribute to variation, as pathologists may use different approaches like “hotspot” counting (focusing on areas of highest proliferation) versus global assessment (averaging across the entire tumor). Studies have shown considerable inter-observer variability when different pathologists score the same tissue samples, particularly in the intermediate range of Ki-67 values (e.g., 10% to 20%). Tumor heterogeneity, where different regions within a single tumor can exhibit varying proliferation rates, adds another layer of complexity to obtaining a representative Ki-67 value. Therefore, while Ki-67 provides valuable information, it is considered one piece of a larger diagnostic picture, and its interpretation requires expertise and consideration of these influencing factors.