Ki67

Definition

Ki67 is a molecule that can be easily detected in growing cells in order to gain an understanding of the rate at which the cells within a tumor are growing.

Purpose

Detection of Ki67 is carried out on biopsies, samples of tumor tissue. The goal of this assay is to evaluate an important characteristic of the cells within the tumor, the percentage of tumor cells that are actively dividing and giving rise to more cancer cells. The number obtained through this examination is termed the S-phase, growth, or proliferative fraction. This information can play an important part in deciding the best treatment for a cancer patient.

Precautions

This test is performed on tissue or cells that have been removed during the initial surgery or diagnostic procedure used to determine the precise nature of the cancer. It usually does not require any new surgery or blood draw on the patient and, so, does not entail any additional precautions for the patient.

Description

Cancer is a group of diseases characterized by abnormal, or neoplastic, cellular growth in particular tissues. In many instances this growth is abnormal because cells are growing more rapidly than is normal. This unregulated growth is how a tumor is formed. A tumor is more or less a collection of cells that grow more rapidly than the surrounding normal tissue. Most importantly, this difference in growth rate is central to how many cancer drugs, termed cytotoxic agents, work. The ability of these drugs to eliminate cancer cells depends on their ability to kill cells that are actively proliferating, but do less damage to cells that are not actively dividing. This makes it useful to know how actively the cells in tumor are growing compared to the surrounding tissue. The measurement of Ki67 is one of the most common ways to measure the growth fraction of tumor cells. This molecule can be detected in the nucleus of only actively growing cells.

Analysis of Ki67 in tumors is accomplished by a pathologist who examines a piece of the tumor tissue using special techniques. The technique used is termed immunocytochemistry. This involves the preparation of a histologic section, a very thin piece of tumor tissue placed on a glass microscope slide. These kinds of tissue sections are used in the diagnosis of cancer. In the case of Ki67 assays, the section is incubated with antibodies that can react with the Ki67 molecule, and then treated with special reagents that cause a color to appear where antibody has bound. In this way, when the pathologist looks at the section using a microscope the fraction of growing cells, whose nuclei are stained for Ki67, can be determined for the tumor cells and compared with the normal tissue. In some instances, depending on the particular type of cancer, the pathologist might feel it more appropriate to use a different technique to assess the growth fraction for a specific tumor or leukemia.

Preparation, Aftercare, and Risks

Because this test is performed on tissue or cells that had been removed during an initial biopsy or other diagnostic procedure, and because no new surgery or sample is required, no additional recommendations regarding preparation, aftercare, or risks are necessary.

Results

The proliferative or growth fraction as determined by Ki67 analysis is interpreted in view of what is normal for the tissue in which the tumor has been found or from which it originated. In the case of certain types of tissue—for example, brain—there is little cellular growth in normal tissue. In other cases, such as breast or the cells that line the colon, cellular growth is a normal part of the function of that tissue. The significance of an increased proliferative fraction is interpreted in light of the experience of the oncologist as well as the knowledge and experience of other clinicians as reported in the medical literature. The Ki67 result, often termed the "Ki67 labeling index, " can be used in some cases as a prognostic indicator for some cancers. For example, for brain tumors, such as astrocytomas and glioblastomas, a high Ki67 labeling index is one factor that predicts a poor prognosis. For breast tumors, the clinician will consider the proliferative fraction in conjunction with other factors such as patient age, results of receptor assays, and whether or not there is evidence of spread of the disease to lymph nodes or other sites within the body. The value of Ki67 is not as firmly established for other cancers such as bladder or pituitary tumors .

Resources

PERIODICALS

Chassevent, A., et al. "S-Phase Fraction and DNA Ploidy in633 T1T2 Breast Cancers: A Standardized Flow Cytometric Study." Clinical Cancer Research 7 (2001): 909-17.

Warren Maltzman, Ph.D.

KEY TERMS

Immunocytochemistry

—Method for staining cells or tissues using antibodies so that the location of a target molecule can be determined

Nucleus

—The part of the cell containing chromosomes

S phase

—The part of the cell division cycle during which the genetic material, DNA, is duplicated

QUESTIONS TO ASK THE DOCTOR

• How far from normal is the Ki-67 labeling index of my tumor?
• To what extent is this result influencing the treatment I will receive?
• In your experience, does the proliferative fraction of my tumor predict a good response to chemotherapy?