From the Guidelines
The Ki-67 proliferative index is a crucial measurement in cancer diagnosis and treatment planning, indicating the percentage of cells actively dividing in a tissue sample, with higher values generally suggesting more aggressive tumors and guiding treatment decisions. The Ki-67 protein is present in cells during all active phases of the cell cycle (G1, S, G2, and M) but absent in resting cells (G0), making it a reliable marker for cell proliferation 1. In clinical practice, pathologists examine tissue samples under a microscope after staining them with antibodies that highlight the Ki-67 protein, then calculate what percentage of cells show positive staining.
Key Points to Consider
- The index is particularly important in cancer diagnosis and treatment planning, as higher Ki-67 values generally indicate more aggressive tumors with faster growth rates.
- Different cancer types have different threshold values that are considered clinically significant, for example, in breast cancer, a Ki-67 index above 20-30% typically suggests a more aggressive tumor that may require more intensive treatment 1.
- The Ki-67 score is defined as the percentage of positively stained cells among the total number of malignant cells scored, with nuclear staining being the focus and cytoplasmic or membrane staining ignored 1.
- Biological heterogeneity of Ki-67 staining can occur across specimens, and the location and extent of the area of the cancer that should be scored is controversial, with recommendations to score at least 1000 cells and accept 500 cells as the absolute minimum 1.
Clinical Application
- The Ki-67 proliferative index helps oncologists determine prognosis and select appropriate therapy options, with higher proliferation rates often warranting more aggressive treatment approaches.
- In mantle cell lymphoma, a Ki-67 cutoff of greater than 30% is used to define poor-risk patients, with the "biologic MIPI" (MIPI-b) combining Ki-67 score with the MIPI to discriminate high-risk from low-risk patients 1.
- Standardization of quantification methods and central review of specimens are crucial for accurate Ki-67 scoring, especially in clinical trials 1.
From the Research
Definition of Ki 67 Proliferative Index
- The Ki-67 proliferative index is a measure of the percentage of cells in a tumor that are actively dividing, as indicated by the presence of the Ki-67 antigen 2, 3, 4, 5, 6.
- It is used to assess the growth fraction of tumors and has been proposed as a useful clinical marker for breast cancer subtype classification, prognosis, and prediction of therapeutic response 3.
Clinical Significance
- A high Ki-67 proliferative index has been associated with poor prognosis in various types of cancer, including breast cancer and non-Hodgkin's lymphoma 4, 5, 6.
- The index can be used to predict the response to neoadjuvant chemotherapy and to evaluate the recurrence-free survival rate of patients 3, 4.
- A cut-off value of 45% can help differentiate indolent from aggressive disease in non-Hodgkin's lymphoma, while a cut-off value of 70% can distinguish patients with a good and bad prognosis in diffuse large B-cell lymphoma 5.
Prognostic Value
- The Ki-67 proliferative index has been shown to be an independent predictor of overall survival and distant disease-free survival in breast cancer patients receiving neoadjuvant treatment 4.
- It has also been found to be a prognostic factor in non-Hodgkin's lymphoma, with a high index associated with worse disease-free survival 5.
- However, the predictive value of the Ki-67 labeling index for response to adjuvant chemotherapy is unclear, and it has not been found to predict better response to adjuvant chemotherapy in some studies 6.