Understanding Tumor Markers-Grades/Prognosis

Understanding Tumor Markers

Tumor markers are substances that can often be detected in higher-than-normal amounts in the blood, urine, or body tissues of some patients with certain types of cancer. Tumor markers are produced either by the tumor itself or by the body in response to the presence of cancer or certain benign (noncancerous) conditions. This fact sheet describes some tumor markers found in the blood.

Measurements of tumor marker levels can be useful—when used along with x-rays or other tests—in the detection and diagnosis of some types of cancer. However, measurements of tumor marker levels alone are not sufficient to diagnose cancer for the following reasons:

  • Tumor marker levels can be elevated in people with benign conditions.
  • Tumor marker levels are not elevated in every person with cancer—especially in the early stages of the disease.
  • Many tumor markers are not specific to a particular type of cancer; the level of a tumor marker can be raised by more than one type of cancer.

In addition to their role in cancer diagnosis, some tumor marker levels are measured before treatment to help doctors plan appropriate therapy. In some types of cancer, tumor marker levels reflect the extent (stage) of the disease and can be useful in predicting how well the disease will respond to treatment. Tumor marker levels may also be measured during treatment to monitor a patient's response to treatment. A decrease or return to normal in the level of a tumor marker may indicate that the cancer has responded favorably to therapy. If the tumor marker level rises, it may indicate that the cancer is growing. Finally, measurements of tumor marker levels may be used after treatment has ended as a part of followup care to check for recurrence.

Currently, the main use of tumor markers is to assess a cancer's response to treatment and to check for recurrence. Scientists continue to study these uses of tumor markers as well as their potential role in the early detection and diagnosis of cancer. The patient's doctor can explain the role of tumor markers in detection, diagnosis, or treatment for that person. Described below are some of the most commonly measured tumor markers.

Prostate-Specific Antigen

Prostate-specific antigen (PSA) is present in low concentrations in the blood of all adult males. It is produced by both normal and abnormal prostate cells. Elevated PSA levels may be found in the blood of men with benign prostate conditions, such as prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH), or with a malignant (cancerous) growth in the prostate. While PSA does not allow doctors to distinguish between benign prostate conditions (which are very common in older men) and cancer, an elevated PSA level may indicate that other tests are necessary to determine whether cancer is present.

PSA levels have been shown to be useful in monitoring the effectiveness of prostate cancer treatment, and in checking for recurrence after treatment has ended. In checking for recurrence, a single test may show a mildly elevated PSA level, which may not be a significant change. Doctors generally look for trends, such as steadily increasing PSA levels in multiple tests over time, rather than focusing on a single elevated result.

Researchers are studying the value of PSA in screening men for prostate cancer (checking for the disease in men who have no symptoms). At this time, it is not known whether using PSA to screen for prostate cancer actually saves lives. The National Cancer Institute-supported Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial is designed to show whether the use of certain screening tests can reduce the number of deaths caused by those cancers. For prostate cancer, this trial is looking at the usefulness of regular screening using digital rectal exams and PSA level checks in men ages 55 to 74.

Researchers are also working on new ways to increase the accuracy of PSA tests. Improving the accuracy of PSA tests could help doctors distinguish BPH from prostate cancer, and thereby avoid unnecessary followup procedures, including biopsies.

Prostatic Acid Phosphatase

Prostatic acid phosphatase (PAP) is normally present only in small amounts in the blood, but may be found at higher levels in some patients with prostate cancer, especially if the cancer has spread beyond the prostate. However, blood levels may also be elevated in patients who have certain benign prostate conditions or early stage cancer.

Although PAP was originally found to be produced by the prostate, elevated PAP levels have since been associated with testicular cancer, leukemia, and non-Hodgkin's lymphoma, as well as noncancerous conditions such as Gaucher's disease, Paget's disease, osteoporosis, cirrhosis of the liver, pulmonary embolism, and hyperparathyroidism.

CA 125

CA 125 is produced by a variety of cells, but particularly by ovarian cancer cells. Studies have shown that many women with ovarian cancer have elevated CA 125 levels. CA 125 is used primarily in the management of treatment for ovarian cancer. In women with ovarian cancer being treated with chemotherapy, a falling CA 125 level generally indicates that the cancer is responding to treatment. Increasing CA 125 levels during or after treatment, on the other hand, may suggest that the cancer is not responding to therapy or that some cancer cells remain in the body. Doctors may also use CA 125 levels to monitor patients for recurrence of ovarian cancer.

Not all women with elevated CA 125 levels have ovarian cancer. CA 125 levels may also be elevated by cancers of the uterus, cervix, pancreas, liver, colon, breast, lung, and digestive tract. Noncancerous conditions that can cause elevated CA 125 levels include endometriosis, pelvic inflammatory disease, peritonitis, pancreatitis, liver disease, and any condition that inflames the pleura (the tissue that surrounds the lungs and lines the chest cavity). Menstruation and pregnancy can also cause an increase in CA 125.

Carcinoembryonic Antigen

Carcinoembryonic antigen (CEA) is normally found in small amounts in the blood of most healthy people, but may become elevated in people who have cancer or some benign conditions. The primary use of CEA is in monitoring colorectal cancer, especially when the disease has spread (metastasized). CEA is also used after treatment to check for recurrence of colorectal cancer. However, a wide variety of other cancers can produce elevated levels of this tumor marker, including melanoma; lymphoma; and cancers of the breast, lung, pancreas, stomach, cervix, bladder, kidney, thyroid, liver, and ovary.

Elevated CEA levels can also occur in patients with noncancerous conditions, including inflammatory bowel disease, pancreatitis, and liver disease. Tobacco use can also contribute to higher-than-normal levels of CEA.


Alpha-fetoprotein (AFP) is normally produced by a developing fetus. AFP levels begin to decrease soon after birth and are usually undetectable in the blood of healthy adults (except during pregnancy). An elevated level of AFP strongly suggests the presence of either primary liver cancer or germ cell cancer (cancer that begins in the cells that give rise to eggs or sperm) of the ovary or testicle. Only rarely do patients with other types of cancer (such as stomach cancer) have elevated levels of AFP. Noncancerous conditions that can cause elevated AFP levels include benign liver conditions, such as cirrhosis or hepatitis; ataxia telangiectasia; Wiscott-Aldrich syndrome; and pregnancy.

Human Chorionic Gonadotropin

Human chorionic gonadotropin (HCG) is normally produced by the placenta during pregnancy. In fact, HCG is sometimes used as a pregnancy test because it increases early within the first trimester. It is also used to screen for choriocarcinoma (a rare cancer of the uterus) in women who are at high risk for the disease, and to monitor the treatment of trophoblastic disease (a rare cancer that develops from an abnormally fertilized egg). Elevated HCG levels may also indicate the presence of cancers of the testis, ovary, liver, stomach, pancreas, and lung. Pregnancy and marijuana use can also cause elevated HCG levels.

CA 19–9

Initially found in colorectal cancer patients, CA 19–9 has also been identified in patients with pancreatic, stomach, and bile duct cancer. Researchers have discovered that, in those who have pancreatic cancer, higher levels of CA 19–9 tend to be associated with more advanced disease. Noncancerous conditions that may elevate CA 19–9 levels include gallstones, pancreatitis, cirrhosis of the liver, and cholecystitis.

CA 15–3

CA 15–3 levels are most useful in following the course of treatment in women diagnosed with breast cancer, especially advanced breast cancer. CA 15–3 levels are rarely elevated in women with early stage breast cancer.

Cancers of the ovary, lung, and prostate may also raise CA 15–3 levels. Elevated levels of CA 15–3 may be associated with noncancerous conditions, such as benign breast or ovarian disease, endometriosis, pelvic inflammatory disease, and hepatitis. Pregnancy and lactation can also cause CA 15–3 levels to rise.

CA 27–29

Similar to the CA 15–3 antigen, CA 27–29 is found in the blood of most breast cancer patients. CA 27–29 levels may be used in conjunction with other procedures (such as mammograms and measurements of other tumor marker levels) to check for recurrence in women previously treated for stage II and stage III breast cancer.

CA 27–29 levels can also be elevated by cancers of the colon, stomach, kidney, lung, ovary, pancreas, uterus, and liver. First trimester pregnancy, endometriosis, ovarian cysts, benign breast disease, kidney disease, and liver disease are noncancerous conditions that can also elevate CA 27–29 levels.

Lactate Dehydrogenase

Lactate dehydrogenase is a protein found throughout the body. Nearly every type of cancer, as well as many other diseases, can cause LDH levels to be elevated. Therefore, this marker cannot be used to diagnose a particular type of cancer.

LDH levels can be used to monitor treatment of some cancers, including testicular cancer, Ewing's sarcoma, non-Hodgkin's lymphoma, and some types of leukemia. Elevated LDH levels can be caused by a number of noncancerous conditions, including heart failure, hypothyroidism, anemia, and lung or liver disease.

Neuron-Specific Enolase

Neuron-specific enolase (NSE) has been detected in patients with neuroblastoma; small cell lung cancer; Wilms' tumor; melanoma; and cancers of the thyroid, kidney, testicle, and pancreas. However, studies of NSE as a tumor marker have concentrated primarily on patients with neuroblastoma and small cell lung cancer. Measurement of NSE level in patients with these two diseases can provide information about the extent of the disease and the patient's prognosis, as well as about the patient's response to treatment.

Understanding Tumor Grades

Grading is a system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions.

Tumor Grade is one of many factors that doctors consider when they develop an individual treatment plan for a cancer patient. Tumor grade refers to the degree of abnormality of cancer cells compared with normal cells.

The body is made up of many types of cells. Normally, cells grow and divide to produce new cells in a controlled and orderly manner. This controlled cell division is the process that heals wounds and replaces aging tissues. Sometimes, however, new cells continue to be produced when they are not needed. As a result, a mass of extra tissue called a tumor may develop. A tumor can be benign (not cancerous) or malignant (cancerous). Cells in malignant tumors are abnormal and grow without control or order. These cancerous cells can invade and destroy the tissue around them and spread.

If a tumor is suspected to be malignant, a doctor removes a sample of tissue or the entire tumor in a procedure called a biopsy. From the biopsy, a pathologist (a doctor who identifies diseases by studying cells under a microscope) can determine whether the tumor is benign or malignant. The pathologist can also identify other characteristics of the tumor cells, including tumor grade and the degree of cell differentiation.

The term "differentiated" describes the extent to which cancer cells are similar in appearance and function to healthy cells of the same tissue type. The degree of differentiation often relates to the clinical behavior of the particular tumor. Grade is a classification system used by pathologists to describe the degree of differentiation of tumor cells. Based on the microscopic appearance of cancer cells, pathologists commonly describe tumor grade by four degrees of severity: Grades 1, 2, 3, and 4. The cells of Grade 1 tumors are often well-differentiated or low-grade tumors, and are generally considered the least aggressive in behavior. Conversely, the cells of Grade 3 or Grade 4 tumors are usually poorly differentiated or undifferentiated high-grade tumors, and are generally the most aggressive in behavior.

The American Joint Commission on Cancer has recommended the following guidelines for grading tumors:

GX Grade cannot be assessed (Undetermined grade)
G1 Well-differentiated (Low grade)
G2 Moderately well-differentiated (Intermediate grade)
G3 Poorly differentiated (High grade)
G4 Undifferentiated (High grade)

Although grade is used by pathologists to describe most types of cancer, its importance in planning treatment and estimating the future course and outcome of disease (prognosis) is greater for certain types of cancers, such as soft tissue sarcoma, primary brain tumors, lymphomas, and breast and prostate cancer.

Some cancers also have special grading systems. For example, pathologists use the Gleason system to describe the degree of differentiation of prostate cancer cells. The Gleason system uses scores ranging from Grade 2 to Grade 10. Lower Gleason scores describe well-differentiated, less aggressive tumors. Higher scores describe poorly-differentiated, more aggressive tumors.

It is important for physicians and patients alike to know as much as possible about a cancer's grade and stage because both the extent to which the disease has progressed (stage), and its microscopic features (grade) are important factors in planning treatment and estimating a patient's prognosis. Patients should discuss questions about tumor grade and how it relates to their diagnosis and treatment with their doctor.

Understanding Prognosis/Cancer Statistics

It is natural for anyone facing cancer to be concerned about what the future holds. Understanding the nature of cancer and what to expect can help patients and their loved ones plan treatment, anticipate lifestyle changes, and make quality of life and financial decisions. Cancer patients frequently ask their doctor or search on their own for statistics to answer the question, "What is my prognosis?"

Prognosis is a prediction of the future course and outcome of a disease and an indication of the likelihood of recovery from that disease. However, it is only a prediction. When doctors discuss a patient's prognosis, they are attempting to project what is likely to occur for that individual patient. The doctor may speak of a favorable prognosis, if the cancer is expected to respond well to treatment, or an unfavorable prognosis, if the cancer is likely to be difficult to control.

A cancer patient's prognosis can be affected by many factors, particularly the type of cancer the patient has, the stage of the cancer (the extent to which the cancer has metastasized, or spread), or its grade (how aggressive the cancer is or how closely the cancer resembles normal tissue). Other factors that may also affect a person's prognosis include the patient's age and general health or the effectiveness of treatment.

Statistics are also used by the doctor to help estimate prognosis. Survival statistics indicate how many people with a certain type and stage of cancer survive the disease. The 5-year survival rates are the most common measure used. They measure the effect of the cancer over a 5 year period of time. Survival rates include persons who survive 5 years after diagnosis, whether in remission, disease-free, or under treatment. It is important to understand that statistics alone cannot be used to predict what will happen to a particular patient because no two patients are exactly alike.

Patients and their loved ones face many uncertainties when dealing with cancer. For some, coping is easier if they know the statistics; for others, statistical information is confusing, fearful, and too impersonal to be of use. The doctor who is most familiar with the patient's situation is in the best position to discuss a patient's prognosis and to help interpret what the statistics may mean for them.

If patients or their loved ones feel they want to know prognostic information, they should talk with the doctor. At the same time, it is important for patients to understand that even the doctor cannot tell them exactly what to expect; in fact, a patient's prognosis may change over time if the cancer progresses, or if treatment is successful.

Seeking prognosis information and understanding statistics can help some patients reduce their fears as they learn more about what their prognosis means for them. It is a personal decision and the patient's choice about how much information to accept and how to deal with it.

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