Tumor Marker

Define the following predictive statistics terms

• True positive

  • a patient tests positive for a condition and actually has the disease

• True negative

  • a patient tests negative and does not have the disease

• False positive

  • a patient tests positive but does not have the disease

• False negative

  • a patient tests negative but does have the disease

• Sensitivity

  • the percent of patients with a disease who test positive

  • Sensitivity=TP/FN+TP​×100%

• Specificity

  • the percent of patients without a disease who test negative

  • Specificity=TN/FP+TN​×100%

• Positive Predictive Value

  • the percent chance that the disease is present if the test result is positive

  • PPV=TP/FP+TP​×100%

• Negative Predictive Value

  • the percent chance that the disease is absent if the test result is negative

  • NPV=TN/FN+TN​×100%

Calculate sensitivity, specificity, positive predictive value, and negative predictive value when provided appropriate statistics about an assay

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Describe the utility of a ROC Curve in evaluating an assay’s diagnostic accuracy

Used to evaluate the diagnostic accuracy of a laboratory assay by relating its sensitivity and specificity at various clinically significant cut points

Use the area under the curve (AUC) from a ROC Curve to determine the diagnostic accuracy of an assay

The closer a curve follows the left-hand border and the top border, the more accurate the test is

Conversely, a curve that stays close to the 45-degree diagonal indicates a less accurate, or "worthless," test.

• 0.90–1.0: Excellent (A)

• 0.80–0.90: Good (B)

• 0.70–0.80: Fair (C)

• 0.60–0.70: Poor (D)

• 0.50–0.60: Fail (F)

Define the following terms

Tumor Marker

• a substance that changes in concentration based on the presence, growth, or activity of a tumor

Neoplasia

• the new growth or the unrestricted growth of cells

Malignant

• an invasive growth that alters the normal physiology at the site of the growth

Benign

• a growth of tissue that is typically non-life threatening and does not migrate to other areas of the body

Metastasis

• process of a neoplastic growth migrating from one location to another within the body

Describe the use of tumor markers as screening, diagnostic, prognostic, and monitoring tools

Screening

• most markers lack the necessary sensitivity and specificity

• Prostate specific antigen is rare exception

Diagnostic

• challenging and is not a straightforward branch of laboratory medicine

prognostic

• case-by-case basis

monitoring tools

• described as the "true power" of tumor marker

List six characteristics of an ideal tumor marker

1. It should be easy and relatively inexpensive to measure.

2. It must be specific to the tumor under investigation.

3. There should be a direct relationship between the levels found in the blood and the tumor mass.

4. It should show abnormal levels even when no other clinical methods are able to reveal the presence of the tumor.

5. The marker should have stable levels within the plasma or urine.

6. It should be absent or found in very low concentrations in individuals who are healthy.

List three enzymes used as tumor markers and the types of tumors associated with each

• Alkaline Phosphatase: This enzyme is associated with primary or secondary liver cancer and bone metastases resulting from prostate or ovarian cancer. Its placental isoenzyme is also found in ovarian, lung, trophoblastic, gastrointestinal (GI), and seminoma tumors.

• Creatine Kinase: Specifically, the CK-1 isoenzyme can be elevated in patients with prostate cancer.

• Lactate Dehydrogenase: This enzyme serves as a marker for liver cancer, leukemia, lymphoma, neuroblastomas, and some types of testicular cancer

List two hormones used as tumor markers and the types of tumors associated with each

• Beta human chorionic gonadotropin (hCG): This hormone is primarily associated with trophoblastic tumors (testicular tumors). It can also be found in elevated levels in patients with breast, gastrointestinal (GI), lung, ovarian, and gastric cancers.

• Calcitonin: This hormone is used as a marker for thyroid, lung, breast, kidney, and liver neoplasms

State the clinical utility and diagnostic cut-points for prostate specific antigen

• PSA is one of the few tumor markers considered effective enough for population-wide screening. It is specifically used to screen all men over 50 years of age.

• Diagnostic Aid: While elevated PSA is associated with prostate cancer, it is also found in cases of benign prostate hypertrophy, leading to some debate regarding its utility. To improve diagnostic accuracy, PSA can be measured in different forms:

  • Total PSA (tPSA): The standard measurement.

  • Free PSA: Used in conjunction with total PSA to calculate a ratio.

  • Complex PSA: Offers slightly higher specificity than total PSA

HIgh Risk: >10.0 ng/mL

Grey zone: 4.0 - 10.0ng/mL

Low risk: < 4.0 ng/mL

List the three forms of prostate specific antigen

• Total PSA (tPSA): This is the standard form measured in most assays.

• Free PSA: This form should only be used in conjunction with the total PSA to calculate a ratio.

• Complex PSA: This form is noted for having a slightly higher specificity than total P

List and describe the tumor markers used for the following types of cancer

Breast Cancer

• CA 15-3 (Carbohydrate Antigen 15-3): Found on the surface of malignant glandular cells, this marker is used as a sensitive and specific way to monitor metastatic breast disease.

• HER-2/neu: This oncogene of the tyrosine kinase family is used in prognostic and predictive modeling. It is rarely elevated in new cases and is specifically used to determine if a patient should be treated with Herceptin.

• BRCA1 and BRCA2: These are markers for genetic predisposition to breast cancer.

• CA 549: While not found in all new cases and present in healthy or pregnant patients, it is highly useful for detecting the recurrence of disease after treatment.

• CA 27.29: This marker has a high predictive value (PPV of 83.3% and NPV of 92.6%) for breast cancer recurrence.

• Other Potential Markers: Breast cancer patients may also show elevations in Carcinoembryonic Antigen (CEA), Calcitonin, and Beta human chorionic gonadotropin (hCG).

Ovarian Cancer

• CA 125: Expressed by epithelial ovarian tumors, this marker is useful for monitoring recurrence and aiding in the differential diagnosis of pelvic masses. It does not have a strong positive predictive value for new disease.

• Alkaline Phosphatase: The placental isoenzyme of this enzyme can be seen in ovarian tumors.

• HER-2/neu: This marker can also be associated with ovarian cancer.

Colorectal Cancer

• Carcinoembryonic Antigen (CEA): Originally found in embryonic tissues, CEA levels are used to monitor the effectiveness of therapy in positive colon cancer patients.

• Guanylyl Cyclase C: This is a unique marker because it is more specific for the colon. It mediates fluid and electrolyte secretion in the intestinal epithelium and continues to be expressed by neoplastic lesions.

• CA 19-9: Helpful in detecting the recurrence of colorectal cancers.

Pancreatic Cancer

• CA 19-9: A derivative of the Lewis A blood group, this marker is normally produced by pancreatic and biliary duct cells. It is used to detect recurrence, though patients who are Lewis A negative will also test negative for this marker.

• CA 50: Another Lewis A antigen derivative, CA 50 is found in 80% to 97% of patients with pancreatic cancer.

• CEA: Serum levels can also be elevated in pancreatic carcinomas.

Bladder Cancer

• Bladder Tumor Antigen: Composed of complexes of basement membrane proteins, these are found in the urine as the tumor infiltrates the bladder or secretes the proteins itself.

• Nuclear Matrix Protein 22: This is part of the internal structure of nuclei and is found in heavy concentrations in the bladder of cancer patients compared to healthy controls.

• HER-2/neu: This oncogene is also seen in cases of bladder cancer

Chose the best tumor marker(s) to monitor a patient when provided a case study

Determine the type of cancer most likely present when given an appropriate case study that includes tumor marker results