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Tumor marker

From Wikipedia, the free encyclopedia
Not to be confused with Cancer biomarker.

Tumor markers are biological molecules (Table 1), such as proteins, carbohydrates, metabolites, and genes, found in bodily fluids or tissues. They can be detected and provide critical information about the presence and progression of cancer, as well as how cancer will respond to treatment.[1] These biomarkers are produced either directly by cancer cells or by the surrounding normal tissue as a response to cancer.[2] They can be normal endogenous molecules, naturally occurring in the body, that are produced in significantly higher amounts in the presence of cancer. Alternatively, they can be molecules of newly activated genes that were inactive in normal cells.[3] Although tumor markers are not sufficient for a definitive diagnosis, they serve as an important complement to imaging and other diagnostic methods.

Table1: Common Tumor Markers and Their Associated Cancers

Tumor marker: Associated cancer:
Prostate-specific antigen (PSA) Prostate carcinoma.[4]
Alfa-fetoprotein (AFP) Hepatocellular carcinoma.[5]
Carcinoembryonic Antigen (CEA) Colon carcinoma.[6]
Lactate dehydrogenase (LDH) Germ cell tumors.[7]
Cancer Antigen 125 (CA 125) Epithelial Ovarian.[7]
Carbohydrate Antigen 19-9 (CA 19-9) Pancreatic.[7]
Chromogranin A (CgA) Neuroendocrine tumors.[7]
Human Epidermal Growth Factor Receptor 2 (HER2/neu) Breast and Ovarian carcinomas.[8]
Breakpoint Cluster Region – Abelson Murine Leukemia Viral Oncogene Homolog 1 (BCR-ABL1) Chronic Myelogenous Leukemia (CML).[9]

Characteristics of ideal Tumor Markers

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An Ideal tumor marker should possess the following characteristics to facilitate early cancer detection, accurate diagnosis and effective monitoring of disease progression and treatment response. It should allow for non-invasive detection, aiding clinicians in making informed decisions regarding patient treatment strategies.

- Organ specificity: it should specifically identify a particular type of cancer.[3]

- Sensitivity: it should be detectable at an early stage of cancer.[2]

- Accuracy: it should minimize false positives and false negatives.[3]

- Prognostic value: the marker’s level should correlate with the cancer’s progression, enabling effective monitoring of treatment response and early detection of cancer recurrence.[3]

- Absence in healthy individuals: ideally, the marker should not be present in healthy individuals.[3]

In addition, the marker should be cancer-specific, meaning it should not be elevated in benign (non-cancerous) conditions. Otherwise, its presence may lead to false positive results, as it could reflect a benign condition rather than malignancy (a cancerous condition).[2]

To improve diagnostic accuracy, clinicians often use a combination of tumor markers. For example, combining CEA with CA 19-9 in pancreatic cancer increases reliability.[10]

However, an ideal tumor marker that fully satisfies all the established criteria has not yet been identified. One notable exception is the BCR-ABL tumor marker, which largely fulfils these requirements. It is found in approximately 95% of patients with clinically diagnosed CML.[11]

BCR-ABL is highly specific to CML and is absent in healthy individuals.[12] As a disease-driving fusion protein, it also serves as a precise therapeutic target. Several tyrosine kinase inhibitors (TKIs), such as imatinib, have been developed to inhibit its activity, demonstrating high treatment efficacy. The BCR-ABL marker exhibits strong prognostic value, as its expression reflects treatment response and enables precise monitoring of disease progression and early detection of recurrence through molecular testing. Additionally, it is highly sensitive and accurate, with minimal false positives, and is not elevated in benign conditions, making it a highly cancer-specific marker.[12]

Despite these strengths, the marker is not entirely ideal, as it is only detectable in CML patients who carry the specific translocation. Approximately 5% of these patients lack the translocation, making the marker unusable in these cases.[11]

Detection method

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Tumor markers are primarily detected in serum using immunoassay techniques, such as ELISA and RIA, which advanced significantly with the introduction of monoclonal antibodies in the 1960s–70s. These antibodies bind to tumor-specific epitopes and are tagged with dyes (IHC), radioisotopes (RIA), or enzymes (ELISA) for detection.[13]

IHC is the most commonly used method in oncology, aiding in tumor classification, identification of metastases, and assessment of prognostic markers like ER/PR in breast cancer. Flow cytometry is also used to quantify antibody-labeled cells in suspension.

Consistency in assay methods is crucial, as different techniques (e.g., IHC vs. DNA sequencing) may yield varying interpretations of biomarkers such as p53.[14]

Clinical Uses

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Tumor markers are not sufficient on their own to establish a definitive cancer diagnosis, but they serve as important tools in clinical oncology. They are used to monitor treatment response, assess disease stage and prognosis, support diagnosis in complex cases, and detect recurrence following therapy:[13]

Monitoring malignancy

  • Involves the use of tumor markers to follow the progression of disease in patients already diagnosed with cancer. By measuring marker levels regularly, clinicians can evaluate the effectiveness of treatments such as chemotherapy or radiation, detect disease progression or stabilization, and make timely adjustments to the therapeutic strategy. For instance, prostate-specific antigen (PSA) is commonly used in prostate cancer patients to track disease activity and treatment response[15].

Tumor staging

  • Tumor markers can provide supplementary information about the extent of the disease. Although not sufficient on their own, elevated levels of specific markers can suggest more advanced or metastatic cancer. For example, high levels of CA 125 in ovarian cancer are often associated with a more advanced stage of the disease.[13]

screening

  • Tumor markers may be used to detect malignancies in individuals without symptoms. For a marker to be useful in screening, it must have high sensitivity (to correctly detect disease) and high specificity (to avoid false positives), and should ideally be specific to a certain organ. An example is PSA, which is used in prostate cancer screening, although its role is debated due to potential overdiagnosis.[15]

Diagnostics

  • Tumor markers are used together with imaging and biopsy to help diagnose cancer. While they cannot confirm cancer on their own, abnormal levels can support suspicion of malignancy and guide further testing. For example, alpha-fetoprotein (AFP) is often elevated in liver cancer, and carcinoembryonic antigen (CEA) is commonly associated with colorectal cancer.[16]

Detection of recurrent

  • Tumor markers are valuable during follow-up after initial treatment to detect cancer recurrence. Regular monitoring can reveal rising marker levels that may indicate relapse, often before symptoms or imaging findings appear. For instance, CA 15-3 is used to monitor breast cancer patients for signs of recurrence.[17]

See also

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References

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  1. ^ Duffy, Michael J. (2012-05-15). "Tumor Markers in Clinical Practice: A Review Focusing on Common Solid Cancers". Medical Principles and Practice. 22 (1): 4–11. doi:10.1159/000338393. ISSN 1011-7571. PMC 5586699. PMID 22584792.
  2. ^ a b c Schrohl, Anne-Sofie; Holten-Andersen, Mads; Sweep, Fred; Schmitt, Manfred; Harbeck, Nadia; Foekens, John; Brünner, Nils (2003-06-01). "Tumor Markers: From Laboratory To Clinical Utility *". Molecular & Cellular Proteomics. 2 (6): 378–387. doi:10.1074/mcp.R300006-MCP200. ISSN 1535-9476. PMID 12813140.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ a b c d e Malati, T. (2007-09-01). "Tumour markers: An overview". Indian Journal of Clinical Biochemistry. 22 (2): 17–31. doi:10.1007/BF02913308. ISSN 0974-0422. PMC 3453798. PMID 23105677.
  4. ^ Balk, Steven P.; Ko, Yoo-Joung; Bubley, Glenn J. (2003-01-15). "Biology of Prostate-Specific Antigen". Journal of Clinical Oncology. 21 (2): 383–391. doi:10.1200/JCO.2003.02.083. ISSN 0732-183X.
  5. ^ Debruyne, Evi N.; Delanghe, Joris R. (2008-09-01). "Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: New aspects and applications". Clinica Chimica Acta. 395 (1): 19–26. doi:10.1016/j.cca.2008.05.010. ISSN 0009-8981.
  6. ^ Malati, T. (2007-09-01). "Tumour markers: An overview". Indian Journal of Clinical Biochemistry. 22 (2): 17–31. doi:10.1007/BF02913308. ISSN 0974-0422. PMC 3453798. PMID 23105677.
  7. ^ a b c d Faria, S. C.; Sagebiel, T.; Patnana, M.; Cox, V.; Viswanathan, C.; Lall, C.; Qayyum, A.; Bhosale, P. R. (2019-04-01). "Tumor markers: myths and facts unfolded". Abdominal Radiology. 44 (4): 1575–1600. doi:10.1007/s00261-018-1845-0. ISSN 2366-0058.
  8. ^ Ménard, S.; Casalini, P.; Campiglio, M.; Pupa, S. M.; Tagliabue, E. (2004-12-01). "Oncogenic protein tyrosine kinases". Cellular and Molecular Life Sciences CMLS. 61 (23): 2965–2978. doi:10.1007/s00018-004-4277-7. ISSN 1420-9071. PMC 11924417. PMID 15583858.
  9. ^ Melo, Junia V. (1996-10-01). "The Diversity of BCR-ABL Fusion Proteins and Their Relationship to Leukemia Phenotype". Blood. 88 (7): 2375–2384. doi:10.1182/blood.V88.7.2375.bloodjournal8872375. ISSN 0006-4971.
  10. ^ Reitz, Daniel; Gerger, Armin; Seidel, Julia; Kornprat, Peter; Samonigg, Hellmut; Stotz, Michael; Szkandera, Joanna; Pichler, Martin (2015-06-01). "Combination of tumour markers CEA and CA19-9 improves the prognostic prediction in patients with pancreatic cancer". Journal of Clinical Pathology. 68 (6): 427–433. doi:10.1136/jclinpath-2014-202451. ISSN 0021-9746. PMID 25759406.
  11. ^ a b Melo, Junia V. (1996-10-01). "The Diversity of BCR-ABL Fusion Proteins and Their Relationship to Leukemia Phenotype". Blood. 88 (7): 2375–2384. doi:10.1182/blood.V88.7.2375.bloodjournal8872375. ISSN 0006-4971.
  12. ^ a b Cilloni, Daniela; Saglio, Giuseppe (2012-02-14). "Molecular Pathways: BCR-ABL". Clinical Cancer Research. 18 (4): 930–937. doi:10.1158/1078-0432.CCR-10-1613. ISSN 1078-0432.
  13. ^ a b c Sharma, S. (2009-01-09). "Tumor markers in clinical practice: General principles and guidelines". Indian Journal of Medical and Paediatric Oncology. 30 (01): 1–8. doi:10.4103/0971-5851.56328. ISSN 0971-5851. PMC 2902207. PMID 20668599.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  14. ^ Zhou, Yue; Tao, Lei; Qiu, Jiahao; Xu, Jing; Yang, Xinyu; Zhang, Yu; Tian, Xinyu; Guan, Xinqi; Cen, Xiaobo; Zhao, Yinglan (2024-05-20). "Tumor biomarkers for diagnosis, prognosis and targeted therapy". Signal Transduction and Targeted Therapy. 9 (1): 1–86. doi:10.1038/s41392-024-01823-2. ISSN 2059-3635.
  15. ^ a b Duffy, Michael J. (2012-05-15). "Tumor Markers in Clinical Practice: A Review Focusing on Common Solid Cancers". Medical Principles and Practice. 22 (1): 4–11. doi:10.1159/000338393. ISSN 1011-7571.
  16. ^ Schrohl, Anne-Sofie; Holten-Andersen, Mads; Sweep, Fred; Schmitt, Manfred; Harbeck, Nadia; Foekens, John; Brünner, Nils (2003-06-01). "Tumor Markers: From Laboratory To Clinical Utility *". Molecular & Cellular Proteomics. 2 (6): 378–387. doi:10.1074/mcp.R300006-MCP200. ISSN 1535-9476. PMID 12813140.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  17. ^ Kabel, Ahmed M. (2017-04-01). "Tumor markers of breast cancer: New prospectives". Journal of Oncological Sciences. 3 (1): 5–11. doi:10.1016/j.jons.2017.01.001. ISSN 2452-3364.
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