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Tumor markers

Last updated: March 25, 2021

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Tumor markers are biological substances that can be detected in the blood, urine, or body tissue of some tumor patients. Although some tumor markers may aid in the diagnosis of cancer, they are primarily used for monitoring treatment response and detecting cancer recurrence. Tumor markers are not reliable screening or diagnostic markers due to their low sensitivity (i.e., not elevated in all cancer patients) and low specificity (i.e., also elevated in benign, noncancerous conditions or otherwise healthy patients). The majority of tumor markers that are used in the clinical setting can be detected in the blood. A number of tumor markers can be detected on tissue histopathology. They are also referred to as immunohistochemical markers and can be detected using immunohistochemical techniques. Gene mutations and patterns of gene expression are also increasingly being used as tumor markers.

For details regarding specific carcinomas and the corresponding tumor markers, see the individual cancer articles.

  • Definition: substances (hormones, enzymes, antigens, immunoglobulins, glycoproteins) that can be detected in the blood, urine, or body tissue of some cancer patients
  • Clinical use
    • Detect cancer (does not confirm diagnosis!)
    • Predict therapeutic responses
    • Monitor the effectiveness of cancer treatment
    • Detection of cancer recurrence and screening
  • Limitations
    • Not all patients with cancer have elevated tumor markers (low sensitivity)
    • Not all patients with elevated tumor markers have cancer! (low specificity)

Tumor markers are generally not used to screen for or diagnose cancer. However, once cancer has been diagnosed via biopsy, tumor markers can be used to predict therapeutic responses and monitor the effectiveness of cancer treatment.

References:[1][2][3][4][5]

Common tumor markers [1][6]
Tumor marker Associated conditions
Alpha fetoprotein (AFP)
β-HCG

Carcinoembryonic antigen (CEA)

Prostate-specific antigen (PSA)
Calcitonin
Alkaline phosphatase
Placental alkaline phosphatase [7]
Lactate dehydrogenase
Neuron specific enolase (NSE)
CA 19–9
CA 15–3 and CA 27–29
CA 125
CA 72-4
Chromogranin A
S-100 protein (S100A) and (S100B)
β2 microglobulin (β2M)
Thyroglobulin
Monoclonal immunoglobulins
Squamous cell carcinoma antigen (SCC) antigen
CYFRA 21-1
DCP (Des-gamma-carboxy prothrombin)
SMRP

Alpha male, HE is a MAN:” the cancers associated with alpha-fetoprotein are Hepatocellular carcinoma, Endodermal sinus tumor (yolk sac tumor), Mixed germ cell tumor, Ataxia-telangiectasia, and Neural tube defects.

β-hCG: Hydatidiform mole, Choriocarcinoma, and Gestational trophoblastic disease are associated with the marker

Abnormal patterns of gene expressions and gene mutations from tissue samples are increasingly being used as tumor markers.

Gene Conditions
ALK gene rearrangement
EGFR gene mutation
HER2neu receptor
Estrogen and progesterone receptors

References:[8]

Overview of immunohistochemical markers [1][9]
Marker Natural occurrence Occurrence in tumors
Vimentin
Desmin
Mesothelin
  • Membrane-bound glycoprotein
Cytokeratin
Neurofilaments
Chromogranin A
Synaptophysin
S-100

GFAP

PSA
TRAP
CD20
CD3
CD8
CD4
CD45

DesMin is associated with muscle tumors like rhabdoMyosarcomas.

ViMEntin is associated with MEsenchymal tumors.

GFAP stains neuroGlial cells, which are affected in Glioblastomas.

  1. Ardini E, Magnaghi P, Orsini P, Galvani A, Menichincheri M. Anaplastic Lymphoma Kinase: Role in specific tumours, and development of small molecule inhibitors for cancer therapy. Cancer Lett. 2010; 299 (2): p.81-94. doi: 10.1016/j.canlet.2010.09.001 . | Open in Read by QxMD
  2. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  3. Campana D, Nori F, Piscitelli L, et al. Chromogranin A: Is it a useful marker of neuroendocrine tumors?. J of Clin Oncol. 2007; 25 (15): p.1967-1973. doi: 10.1200/jco.2006.10.1535 . | Open in Read by QxMD
  4. Nielsen OS, Munro AJ, Duncan W, et al. Is placental alkaline phosphatase (PLAP) a useful marker for seminoma?. Eur J Cancer. 1990; 26 (10): p.1049-54. doi: 10.1016/0277-5379(90)90049-y . | Open in Read by QxMD
  5. Painter JT, Clayton NP, Herbert RA. Useful immunohistochemical markers of tumor differentiation. Toxicol Pathol. 2010; 38 (1): p.131-141. doi: 10.1177/0192623309356449 . | Open in Read by QxMD
  6. Tumor Markers. https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet. Updated: November 4, 2015. Accessed: February 18, 2017.
  7. Tumor Markers. https://labtestsonline.org/understanding/analytes/tumor-markers/start/2. Updated: April 13, 2016. Accessed: February 18, 2017.
  8. Diamandis EP, Fritsche HA, Lilja H, Chan DW, Schwartz MK. Tumor Markers: Physiology, Pathobiology, Technology, and Clinical Applications. American Association for Clinical Chemistry ; 2002
  9. Ying ACH, Kie AS, Leung LC, Tong NW. Cancer Screening, Early Detection and Prevention Guidelines For Health Professionals. Hong Kong Anti-Cancer Society ; 2011
  10. Le T, Bhushan V. First Aid for the USMLE Step 1 2015. McGraw-Hill Education ; 2014