Cancer and Tumor Markers Overview

Cancer and Tumor Markers

• Cancer is the uncontrolled growth and spread of abnormal cells in the body.
• Cancer is a group of more than 200 different diseases.
• Cancer is identified by uncontrolled cell growth and proliferation.
• Initially, a tumor cell may be located and contained (benign).
• Invasive tumor cells spread into surrounding tissue and blood vessels.

Malignant Tumors

• Malignant tumors are cancers. Tumor cells invade and damage tissues and organs nearby.
• Mutations in benign cells allow for invasion of tissues and spread to other parts of the body (metastasis).
• Examples of how malignant tumor cells behave differently than normal cells include:
  • Decreased cell-cell interactions and adhesion within the affected tissues.
  • Increased production of proteases to aid in the movement of abnormal cells through tissues.

Benign Tumors

• Benign tumors are not cancer.
• They can be removed and in most cases do not return.
• Most importantly, cells from benign tumors stay in one location and do not spread.
• Examples of benign tumors:
  • Adenoma (glands)
  • Myoma (muscle tissue)
  • Lipoma (fatty tissue)
  • Angioma (small blood or lymph vessels-e.g. a birthmark)
  • Chondroma (cartilage)

Characteristics of Benign and Malignant Tumors

Stages of Cancer

• Stage 1: Confined to organ of origin.
• Stage 2: Locally invasive.
• Stage 3: Spread to lymph nodes.
• Stage 4: Spread to distant sites.

Tumor Markers

• A tumor marker is a substance (protein, enzyme, etc.) produced by a tumor or the host in response to a tumor.
• Tumor markers can be used to differentiate a tumor from normal tissue.
• Tumor markers can be used to detect the presence of a tumor.
• Tumor markers include substances found in cells, tissues, or body fluids.
• These substances can be measured qualitatively or quantitatively using chemical, immunological, or molecular diagnostic methods.
• Tumor cells multiplying, cancer spreading, and tissue damage causes an increase and release of tumor markers into the bloodstream.
• The measurement of tumor markers is useful in tumor diagnosis.
• The measurement of tumor markers is used to follow the efficiency of treatment.
• The measurement of tumor markers can be used to predict the response to therapy.

Diagnostic Methods for Neoplasia

• Family history and direct examination (symptoms like weight loss, fatigue, etc.)
• Radiographic techniques (x-rays, CT, MRI, Mammography, Ultrasound, PET scan.)
• Pathological diagnostic procedures (FNA, biopsy, cytological smears)
• Biochemical assays and genetic methods (tumor markers)

Methods used to measure Tumor Markers

• Immunoassays (e.g., ELISA)
• HPLC
• Immunohistochemistry
• Enzyme assays
• Molecular biology methods

Types of Tumor Markers

• Cell surface antigens
• Cytoplasmic proteins
• Enzymes
• Hormones
• Oncofetal antigens
• Receptors
• RNA or DNA biomarkers
• Gene expression markers

The Ideal Tumor Marker

• Specific for a tumor (few markers specific for individual tumors).
• Sensitive: detect small tumors to allow early diagnosis or screening.
• Level should change in response to tumor size.
• Levels in healthy individuals are much lower than in cancer.
• Easily and reproducibly measured.
• Determination is not expensive.
• No known tumor marker has 100% sensitivity and specificity.
• In practice, tumor markers are most useful in evaluating disease progression after initial therapy and monitoring subsequent treatment.

Urinary Tumor Markers

• Various urinary markers are associated with various malignancies (e.g., Polyamines, Vanillylmandelic acid, etc.)

CSF Tumor Markers

• Tumor markers in cerebrospinal fluid (CSF) are linked to malignancies that have metastasized to the central nervous system (CNS).

False Results in Tumor Markers

• False Positive Results:*
• Inflammatory conditions
• Benign conditions
• Liver diseases (affect metabolism and excretion of tumor markers)
• Renal function disturbances
• Physiological conditions (pregnancy)
• False Negative Results:*
• Insufficient expression of antigen in tumor cells
• Insufficient blood circulation in the tumor
• Rapid antigen degradation

Limitations of the Use of Tumor Markers

• Tumor markers are not ideal for diagnosing cancer
• False positive results: individuals without cancer may have elevated levels of the marker.
• False negative results: tumor markers may not be sufficiently elevated in all individuals with cancer.
• Examples of false results: Prostate-specific antigen (PSA) is elevated in benign prostate hypertrophy, so additional testing is needed.

More Accurate Tumor Markers

• Patterns of gene expression and changes in DNA sequences are increasingly used as tissue-specific markers.
• Proteomics (the study of protein structure, function and patterns of expression) to develop biomarkers for early disease identification, effectiveness of treatment, and recurrence prediction.

Advances in Tumor Biomarkers

• Genomics and proteomics approaches
• Complementary DNA (cDNA)
• microRNA (miRNA) biomarkers
• Long non-coding RNA (LncRNA) biomarkers
• Protein, and tissue microarray
• Mass spectrometry (MS)
• Bioinformatics tools
• Serum proteomics

Selected Molecular Markers of Cancer

• Various markers (DNA, RNA, protein) are associated with specific cancers.

Common Serum Markers for Cancer Diagnosis/Prognosis

• A table showing which serum markers are associated with various cancers

Tumor Markers Used for Cancer Treatment

• Determining the effectiveness of cancer treatment
• Detecting tumor recurrence or remission

Some Common Tumor Markers

• Table showing analyte and cancer use for common markers (e.g., CEA, CA-125, CA15-3, AFP, total PSA, free PSA, hCG, hormone receptors)

Tumor Marker Descriptions

• Various tumor markers (alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (B-HCG), carbohydrate antigen 125 (CA 125), carbohydrate antigen 19-9 (CA 19-9), carbohydrate antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA), lactate dehydrogenase (LD) are described with their corresponding conditions and cancer types.

Classification of Tumor Markers

• Oncofetal proteins (e.g., AFP, hCG, CEA)
• Carbohydrate antigens (e.g., CA-125, CA-19-9)
• Enzymes (e.g., ALP, LDH, amylase, creatine kinase, PSA, PAP)
• Hormones and hormone receptors
• Proteins (e.g., B2-microglobulin, ferritin)
• Genetic markers (e.g., mutated oncogenes, tumor suppressor genes)

Oncofetal proteins (e.g., Alpha-fetoprotein (AFP)

• AFP is a fetal serum protein.
• AFP levels are normally low in adults.
• Elevated AFP levels are associated with hepatocellular carcinoma (HCC) and other conditions like acute hepatitis.

Enzymes as Tumor Markers

• Alkaline phosphatase (ALP) is associated with liver, bone, and placenta.
• Lactate dehydrogenase (LDH) is nonspecific and found in various cancers including liver and leukemia.

Prostate-Specific Antigen (PSA)

• PSA is the only marker used for screening prostate cancer.
• Tissue-specific marker found in prostate epithelium.
• PSA function: semen liquefaction.
• Highly sensitive marker for prostate cancer.
• Elevation is linked to stage, tumor size, recurrence, and response to treatment.
• Elevated in benign conditions (e.g., benign prostatic hyperplasia).

Hormones (examples)

• Insulin, calcitonin, catecholamines, ectopic ACTH and ADH from lung cancers
• Human chorionic gonadotropin (hCG): pregnancy, elevated levels associated with cancers
• Important Note: Tumor markers are not ideal markers for diagnosis and need to be interpreted with other diagnostic tools.

In Conclusion

• No serum marker is specific for malignancy at present.
• Markers are rarely elevated in early-stage malignancy.
• Markers are good for monitoring response to treatment and recurrence.
• Cancer markers are most useful in combination with comprehensive medical evaluations.