Tumor Markers

• 2nd leading cause of mortality in developed countries • 42% males and 38% females will develop invasive cancer in lifetime • Lifetime risk of dying of cancer 23% male and 19% female • Rates higher in marginalized groups (racial/ethnic/sexual orientation)

• Proliferation • Transformation • Invasion • Metastasis • Vascularization (solid tumors)

Stage 1: Epithelium with tumor cells Stage 2: Invasion of primary tumor thru epithelium and into blood vessels Stage 3: Migration of tumor into regional lymph nodes Stage 4: Metastasis and invasion of tumor to distant tissues

• Biomarker found in the blood or tissue and when elevated is linked to cancer • Tumor produces it OR marker is effect of tumor on healthy tissue • Examples: hormones, metabolites, receptors, enzymes, oncofetal antigens

Protein produced during fetal development and elevated in individuals with cancer

• Elevated non-specifically • Largely a result of high metabolic demand of tumor cells • Tend to correlate with tumor burden • Clinically useful for monitoring therapy success

• Beta-macroglobulin • Immunoglobulins

• Found on surface of all nucleated cells • Used as non-specific marker of the high cell turnover common in tumors

• Multiple myeloma • Provides relatively specific measure of plasma cell production of monoclonal proteins

• Used in endocrine malignancies • Valuable in diagnosing neuroblastomas, pituitary, and adrenal adenomas • Examples: ACTH, ADH, calcitonin, cortisol, PTH…etc

• One of first classes of tumor markers • Expressed transiently during normal development BUT turned on again in formation of tumors • Ag: Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP)

• Monoclonal defined antigens identified from human tumor extracts and cell lines • There are Ab created to target specific carb or cancer Ag • Best used for monitoring treatment of tumors that secrete these epitopes

• Receptors that are used to classify tumors for therapy • Non-serological markers • Helps to choose between endocrine and cytotoxic therapies

• Tumor specific • Absent in healthy individuals • Readily detectable in body fluids

• Numerous markers ID have high enough sensitivity AND specificity to aid diagnosis, prognosis, detection of recurrence, and/or monitoring response to treatment • Used in combo with clinical signs, symptoms, and histology to facilitate clinical decision making

• Weigh benefits of disease detection vs harms of overtreatment (avoid false positives) • No tumor marker can effectively screen asymptomatic populations • Most found in normal and benign cells as well as cancer • Targeted screening • Family history of disease

• ID germline mutations (breast, ovarian, colon) • Breast and ovarian: BRCA1 and BRCA2 • Familial colon cancers: APC gene develop cancer by 40 by 99%

• [Tumor marker] generally increases with tumor progression • Highest levels with metastasis • Levels at diagnosis reflect aggressiveness, may predict outcome/indicate malignancy and metastasis • Presence or absence may be valuable • Can help determine best treatment options

False. More common in women than men

• Tumor marker levels can be used to help monitor therapy and can be followed serially • Many tumor markers have lead time of several months vs other methods such as imaging • Earlier indication of relapse

• Differences in Ab specificity • Analyte heterogeneity -Assay design • Lack of standardized reference material • Calibration • Kinetics • Reference range variation

True

• Immunoassays • HPLC • Immunohistochemistry/immunofluorescence • Enzyme assays

• AFP • Cancer Antigen 125 (CA-125) • Carcinoembryonic Ag (CEA) • Human Chorionic Gonadotropin (hCG) • Prostate Specific Ag (PSA) • CA-15-3 • Immunoglobulin Free Light Chains (FLC) • Human Epididymis Protein 4 (HE4) • Neuron-Specific Enolase (NSE)