Receptor analysis

Definition

Receptor analysis is a diagnostic test that determines an important biological characteristic of the cells in a tumor—their response to normal growth factors.

Purpose

The goal of receptor analysis is to reveal whether the cancer cells in a tumor have specific molecules, termed receptors, on the cell surface. This test is routinely performed for breast cancer , as well as other tumors. Information as to the presence of these specific receptors can play a role in deciding the best course of treatment for a particular patient.

Precautions

Because this test is performed on a piece of tissue that has already been removed during a surgical or diagnostic procedure, it does not require any precautionary measures on behalf of the patient.

Description

The cancer cells found in tumors or in the blood of leukemia patients can differ in many ways, and to varying degrees from the corresponding cells in normal tissues and blood. In some respects, cancer treatment depends upon the differences in behavior between tumor and normal cells. For example, tumor cells often grow faster than normal (non-cancerous) cells. The changes that occur as normal cells become cancerous are progressive. As a tumor develops the cells generally become less similar to normal cells and behave in a biologically different way. Some cancer treatments make use of the ways that cancer cells in a tumor can be like cells in the normal surrounding tissue.

One the most fundamental ways in which the early stages of some cancers resemble healthy tissue is that the growth of the cells in the tumor responds to some of the same factors that control the growth of normal tissues. The most common example of this is the response of breast cancer cells to estrogen. During the normal menstrual cycle, the mammary glands respond to changes in the levels of two hormones, estrogen and progesterone. In many cases, the growth of breast cancer tumor cells also responds to the presence or absence of estrogen. The response of both normal and tumor cells to these hormones depends upon presence of molecules termed estrogen and progesterone receptors. If cells in a breast tumor have these receptors, it is possible to inhibit the growth of the cancer cells by preventing estrogen from stimulating their growth. This is generally accomplished through the use of anti-estrogen drugs such as tamoxifen .

Receptor analysis usually involves a special technique, called immunocytochemistry, to examine a small piece of the tumor tissue. A tissue section, a very slice of the tumor, is placed on a glass microscope slide. These tissue sections, which are very similar to those used in the initial diagnosis of the patient's breast cancer, are incubated with antibody preparations that will react with estrogen and progesterone receptors. Special reagents that lead to a chemical reaction where these antibodies are bound produce a visible color in cells that have hormone receptors. A pathologist then looks at the section with a microscope to determine the percentage of tumor cells that are receptor-positive. This information can be used to decide whether a woman with breast cancer should be treated with anti-estrogens. In addition, the presence of estrogen receptors is itself an accepted prognostic indicator. Tumors that have high levels estrogen receptors are generally less aggressive. Taken together with information as to the patient's age, the size and grade of the tumor, and whether or not there is lymph node involvement, it is possible for a doctor to have some idea as to the likelihood the patient will remain disease-free after initial treatment.

Estrogen receptor analysis is an important and generally accepted part of managing breast cancer. More recently, assays for other cell surface receptors have been explored and introduced for the management of breast and other cancers. Examples of these include androgen receptors in prostate cancer and epidermal growth factor receptor (EGFR) in a variety of cancers. In 2001 the most prominent example of a receptor assay, other than estrogen receptor analysis, is testing for a cell surface molecule designated HER2. Patients whose tumors express higher than normal amounts of HER2 are believed to have worse prognoses. However, these patients may be treated with a specific reagent, a monoclonal antibody, which is targeted toward the HER2 protein. Analysis for HER2 can be performed in a similar way to estrogen receptor immunocytochemical assays, currently marketed as the HercepTest, or by using a different type of test that directly examines the gene for HER2. Treatment with the monoclonal antibody to HER2 can improve the survival of patients that express higher than normal levels of HER2 in their tumor cells

Risks

This test is performed on a piece of tissue that has been removed during the initial surgery or diagnostic procedure used to establish the nature of the tumor. It does not require any new surgery on the patient and, so, does not entail any risk to the patient.

Results

Receptor assays measure molecules that play normal and essential roles in the natural function of various tissues. Abnormal results depend upon the particular tissue and the type of cancer involved. The presence of the appropriate receptor, for example estrogen receptors in breast tumors, may be indicative that the cancer can be treated with compounds that can inhibit the growth of the cells that make up the tumor. In other cases, receptor assays may enable a doctor to know the origin of a tumor. That is, sometimes it is not possible for a pathologist to examine a biopsy and be certain what type of cancer a tumor represents. Knowing the identity of the receptors found on the tumor cells may then provide important information for establishing the diagnosis and best course of treatment for such patients.

Resources

PERIODICALS

Chang J., et al. "Prediction of Clinical Outcome from Primary Tamoxifen by Expression of Biologic Markers in Breast Cancer Patients." Clinical Cancer Research 6 (2000): 616-21.

Slamon, D., et al. "Use of Chemotherapy Plus a Monoclonal Antibody Against HER-2 for Metastatic Breast Cancer that Overexpresses HER 2." New England Journal of Medicine 344 (March 2001): 783-92.

OTHER

"HercepTest Frequently Asked Questions." DAKO Corporation 24 July 2001 <http://www.dakousa.com/herinfo/hctfaqs.htm>.

Warren Maltzman, Ph.D.

KEY TERMS

Anti-estrogen

—A drug, for example tamoxifen, that prevents the hormone estrogen from influencing the behavior of specific types of cells.

Biopsy

—A piece of tissue removed for diagnostic examination.

Receptors

—Molecules, usually found on the surface of a cell, that are required for cells to be influenced by hormones and other growth factors.

QUESTIONS TO ASK THE DOCTOR

• What fraction of the cells in my tumor has normal receptors?
• Do the results of the receptor assay on the biopsy of my tumor make me a candidate for anti-estrogen treatment?
• How do the results of the receptor assays on my tumor influence your decision as to my treatment and prognosis?