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Tumor marker

Proxy markers for certain cancers


Proxy markers for certain cancers

A tumor marker is a biomarker that can be used to indicate the presence of cancer or the behavior of cancers (measure progression or response to therapy). They can be found in bodily fluids or tissue. Markers can help with assessing prognosis, surveilling patients after surgical removal of tumors, and even predicting drug-response and monitor therapy.

Tumor markers can be molecules that are produced in higher amounts by cancer cells than normal cells, but can also be produced by other cells from a reaction with the cancer.

The markers can't be used to give patients a diagnosis but can be compared with the result of other tests like biopsy or imaging.

Classification

Tumor markers can be proteins, carbohydrates, receptors and gene products. Proteins include hormones and enzymes. To detect enzyme tumor markers enzyme activity is measured. They were previously widely used, but they have largely been replaced by oncofetal antigens and monoclonal antibodies, due to disadvantages such as most of them lacking organ specificity. Carbohydrates consist of antigens on and/or secreted from tumor cells, these are either high-molecular weight mucins or blood group antigens. Receptors are used to determine prognosis and measure how the patient responds to treatment, while genes or gene products can be analyzed to identify mutations in the genome or altered gene expression.

Uses

Tumor markers may be used for the following purposes:

  • Monitoring the malignancy: When a malignant tumor is found by the presence of a tumor marker, the level of marker found in the body can be monitored to determine the state of the tumor and how it responds to treatment. If the quantity stays the same during treatment it can indicate that the treatment isn't working, and an alternative treatment should be considered. Rising levels of tumor marker does not necessarily reflect a growing malignancy but can result from things like unrelated illnesses.
  • Reflect the stage of cancer: By determining the stage of cancer, it's possible to give a prognosis and treatment plan.
  • Screening for cancers: No screening test is wholly specific, and a high level of tumor marker can still be found in benign tumors. The only tumor marker currently used in screening is PSA (prostate-specific antigen).
  • Diagnostics: Tumor markers alone can't be used for diagnostic purposes, due to lack of sensitivity and specificity. The only approved diagnostic method for cancer is with a biopsy.
  • Detects reoccurring cancers: Tumor markers can detect reoccurring cancers in patients post-treatment.

Techniques

Tumor markers can be determined in serum or rarely in urine or other body fluids, often by immunoassay, ⁣⁣ but other techniques such as enzyme activity determination are sometimes used. Assaying tumor markers were significantly improved after the creation of ELISA and RIA techniques and the advancement of monoclonal antibodies in the 1960s and 1970s.

For many assays, different assay techniques are available. It is important that the same assay is used, as the results from different assays are generally not comparable. For example, mutations of the p53 gene can be detected through immunohistochemical polymorphism screening of DNA, sequence analysis of DNA, or by single-strand conformational polymorphism screening of DNA. Each assay may give different results of the clinical value of the p53 mutations as a prognostic factor.

Interlaboratory proficiency testing for tumor marker tests, and for clinical tests more generally, is routine in Europe and an emerging field in the United States. New York state is prominent in advocating such research.

List of commonly used markers

Tumor markerAssociated tumor types
Alpha fetoprotein (AFP)chapter=Appendix C2: Selected Immunohistochemical Tumor Markerspages=746–747chapter-url=editor1-last=Casciatoeditor1-first=Dennis Alberteditor2-last=Territoeditor2-first=Mary C.title=Manual of Clinical Oncologydate=2009publisher=Lippincott Williams & Wilkinsisbn=978-0-7817-6884-9 }}
CA15-3breast cancer
CA27.29breast cancer
CA19-9Mainly pancreatic cancer, but also colorectal cancer and other types of gastrointestinal cancer.
CA-125last1=Osmanfirst1=N.last2=O'Learyfirst2=N.last3=Mulcahyfirst3=E.last4=Barrettfirst4=N.last5=Wallisfirst5=F.last6=Hickeyfirst6=K.last7=Guptafirst7=R.title=Correlation of serum CA125 with stage, grade and survival of patients with epithelial ovarian cancer at a single centrejournal=Irish Medical Journaldate=September 2008volume=101issue=8pages=245–247pmid=18990955oclc=270998384 }} but may also be elevated in for example endometrial cancer, fallopian tube cancer, lung cancer, breast cancer and gastrointestinal cancer.
Calcitoninmedullary thyroid carcinoma
Calretininmesothelioma, sex cord-gonadal stromal tumor, adrenocortical carcinoma, synovial sarcoma
Carcinoembryonic antigen (CEA)gastrointestinal cancer, cervical cancer, lung cancer, ovarian cancer, breast cancer, urinary tract cancer
CD34hemangiopericytoma/solitary fibrous tumor, pleomorphic lipoma, gastrointestinal stromal tumor, dermatofibrosarcoma protuberans
CD99Ewing sarcoma, primitive neuroectodermal tumor, hemangiopericytoma/solitary fibrous tumor, synovial sarcoma, lymphoma, leukemia, sex cord-gonadal stromal tumor
CD117gastrointestinal stromal tumor, mastocytosis, seminoma
Chromograninneuroendocrine tumor
Chromosomes 3, 7, 17, and 9p21bladder cancer
CytokeratinMany types of carcinoma, some types of sarcoma
Desminsmooth muscle sarcoma, skeletal muscle sarcoma, endometrial stromal sarcoma
Epithelial membrane antigen (EMA)many types of carcinoma, meningioma, some types of sarcoma
Factor VIII; CD31, FL1, CD34vascular sarcoma
Glial fibrillary acidic protein (GFAP)glioma (astrocytoma, ependymoma)
Gross cystic disease fluid protein (GCDFP-15)breast cancer, ovarian cancer, salivary gland cancer
HMB-45melanoma, PEComa (for example angiomyolipoma), clear cell carcinoma, adrenocortical carcinoma
Human chorionic gonadotropin (hCG)gestational trophoblastic disease, germ cell tumor, choriocarcinoma
immunoglobulinlymphoma, leukemia
inhibinsex cord-gonadal stromal tumor, adrenocortical carcinoma, hemangioblastoma
keratin (various types)carcinoma, some types of sarcoma
lymphocyte marker (various types)lymphoma, leukemia
MART-1 (Melan-A)melanoma, steroid-producing tumors (adrenocortical carcinoma, gonadal tumor)
Myo D1rhabdomyosarcoma, small-blue-round-cell tumor
muscle-specific actin (MSA)myosarcoma (leiomyosarcoma, rhabdomyosarcoma)
neurofilamentneuroendocrine tumor; small-cell carcinoma of the lung
neuron-specific enolase (NSE)neuroendocrine tumor; small-cell carcinoma of the lung, breast cancer
placental alkaline phosphatase (PLAP)seminoma, dysgerminoma, embryonal carcinoma
prostate-specific antigen (PSA)prostate
S100 proteinmelanoma, sarcoma (neurosarcoma, lipoma, chondrosarcoma), astrocytoma, gastrointestinal stromal tumor, salivary gland cancer, some types of adenocarcinoma, histiocytic tumor (dendritic cell, macrophage)
smooth muscle actin (SMA)gastrointestinal stromal tumor, leiomyosarcoma, PEComa
synaptophysinneuroendocrine tumor
thymidine kinaselymphoma, leukemia, lung cancer, prostate cancer
thyroglobulin (Tg)post-operative marker of thyroid cancer (but not in medullary thyroid cancer)
thyroid transcription factor-1 (TTF-1)all types of thyroid cancer, lung cancer
Tumor M2-PKdoi=10.1038/sj.bjc.6603712title=Tumour M2-PK as a stool marker for colorectal cancer: Comparative analysis in a large sample of unselected older adults vs colorectal cancer patientsyear=2007last1=Haugfirst1=Ulast2=Rothenbacherfirst2=Dlast3=Wentefirst3=M Nlast4=Seilerfirst4=C Mlast5=Stegmaierfirst5=Clast6=Brennerfirst6=Hjournal=British Journal of Cancerpmid=17406361pmc=2360192volume=96issue=9pages=1329–34}} Breast cancer, renal cell carcinoma lung cancer, pancreatic cancer, esophageal cancer, stomach cancer,cervical cancer, ovarian cancer,
vimentinsarcoma, renal cell carcinoma, endometrial cancer, lung carcinoma, lymphoma, leukemia, melanoma

Accuracy and specific use

The ideal tumor marker has the following characteristics:

  • Specificity to a certain type of tumor
  • Should detect the malignancy earlier than a clinical diagnosis
  • Be highly sensitive to avoid false positives
  • The level of tumor marker should indicate the state of the malignancy to be able to monitor treatment response.

An ideal tumor marker does not exist, and how they are clinically applied depends on the specific tumor marker. For example, tumor markers like Ki-67 can be used to choose form of treatment or in prognostics but are not useful to give a diagnosis, while other tumor markers have the opposite functionality. Therefore it's important to follow the guidelines of the specific tumor marker.

Tumor markers are mainly used in clinical medicine to support a diagnosis and monitor the state of malignancy or reocurrence of cancer.

References

References

  1. (April 2019). "Tumor markers: myths and facts unfolded". Abdominal Radiology.
  2. "Tumor Marker Tests: MedlinePlus Medical Test".
  3. (2020). "Tumor markers". Academic Press.
  4. (2016). "Tumor markers: A diagnostic tool". National Journal of Maxillofacial Surgery.
  5. Sharma, S.. (2009). "Tumor markers in clinical practice: General principles and guidelines". Indian Journal of Medical and Paediatric Oncology.
  6. (16 October 1996). "Tumor Marker Utility Grading System: a Framework to Evaluate Clinical Utility of Tumor Markers". JNCI Journal of the National Cancer Institute.
  7. (15 March 1992). "Molecular marker test standardization". Cancer.
  8. (1998). "Promoting Safe and Effective Genetic Testing in the United States: Final Report of the Task Force on Genetic Testing". Johns Hopkins University Press.
  9. (2009). "Manual of Clinical Oncology". Lippincott Williams & Wilkins.
  10. (2006). "CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: A combined analysis of seven International Breast Cancer Study Group trials". Annals of Oncology.
  11. (February 2001). "CA27.29". European Journal of Cancer.
  12. (27 December 2020). "Carbohydrate antigen 19-9 — tumor marker: Past, present, and future". World Journal of Gastrointestinal Surgery.
  13. (September 2008). "Correlation of serum CA125 with stage, grade and survival of patients with epithelial ovarian cancer at a single centre". Irish Medical Journal.
  14. (October 1998). "CA 125: The past and the Future". The International Journal of Biological Markers.
  15. (2011). "Serum calcitonin levels with calcium loading tests before and after total thyroidectomy in patients with thyroid diseases other than medullary thyroid carcinoma". Endocrine Journal.
  16. (February 2014). "Diagnosis of bladder cancer from the voided urine specimens using multi-target fluorescence in situ hybridization". Oncology Letters.
  17. (July 1992). "Thymidine kinase: a tumor marker with prognostic value for non-Hodgkin's lymphoma and a broad range of potential clinical applications". Annals of Hematology.
  18. (2007). "Tumour M2-PK as a stool marker for colorectal cancer: Comparative analysis in a large sample of unselected older adults vs colorectal cancer patients". British Journal of Cancer.
  19. (2000). "Tumor type M2 pyruvate kinase expression in advanced breast cancer". Anticancer Research.
  20. (May 2010). "The Clinicopathological and Prognostic Relevance of Pyruvate Kinase M2 and pAkt Expression in Breast Cancer". Anticancer Research.
  21. (1999). "Marker for renal cell carcinoma (RCC): The dimeric form of pyruvate kinase type M2 (Tu M2-PK)". Anticancer Research.
  22. (February 2003). "Fuzzy logic-based tumor marker profiles improved sensitivity of the detection of progression in small-cell lung cancer patients". Clinical and Experimental Medicine.
  23. (2007). "Значение маркера опухоли TU M2-PK в диагностике рака легких". Клиническая медицина.
  24. (2000). "Tumor M2-pyruvate kinase: A promising tumor marker in the diagnosis of gastro-intestinal cancer". Anticancer Research.
  25. (2007). "Tumour M2-pyruvate kinase: A gastrointestinal cancer marker". European Journal of Gastroenterology & Hepatology.
  26. (2004). "Evaluation of the Pyruvate Kinase isoenzyme tumor (Tu M2-PK) as a tumor marker for cervical carcinoma". The Journal of Obstetrics and Gynaecology Research.
  27. (2007). "M2-PK as a novel marker in ovarian cancer. A prospective cohort study". European Journal of Gynaecological Oncology.
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