Tumor marker explained

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.[1]

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 They were previously widely used, but they have largely been replaced by oncofetal antigens and monoclonal antibodies, due to disadvantages such as most of them lacking organ specificity.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 consists 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 product can be analyzed to identify mutations in the genome or altered gene expression.[2]

Uses

Tumor markers may be used for the following purposes:

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.

By determining the stage of cancer, it's possible to give a prognosis and treatment plan.[3]

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).

Tumor markers alone can't be used for diagnostic purposes, due to lack of sensitivity and specificity.[4] The only approved diagnostic method for cancer is with a biopsy.

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.[5]

Interlaboratory proficiency testing for tumor marker tests, and for clinical tests more generally, is routine in Europe and an emerging field[6] in the United States. New York state is prominent in advocating such research.[7]

List of commonly used markers

Tumor marker Associated tumor types
Alpha fetoprotein (AFP) germ cell tumor, hepatocellular carcinoma[8]
breast cancer[9]
breast cancer[10]
Mainly pancreatic cancer, but also colorectal cancer and other types of gastrointestinal cancer.[11]
Mainly ovarian cancer,[12] but may also be elevated in for example endometrial cancer, fallopian tube cancer, lung cancer, breast cancer and gastrointestinal cancer.[13]
medullary thyroid carcinoma[14]
mesothelioma, sex cord-gonadal stromal tumor, adrenocortical carcinoma, synovial sarcoma
Carcinoembryonic antigen (CEA) gastrointestinal cancer, cervix cancer, lung cancer, ovarian cancer, breast cancer, urinary tract cancer
hemangiopericytoma/solitary fibrous tumor, pleomorphic lipoma, gastrointestinal stromal tumor, dermatofibrosarcoma protuberans
Ewing sarcoma, primitive neuroectodermal tumor, hemangiopericytoma/solitary fibrous tumor, synovial sarcoma, lymphoma, leukemia, sex cord-gonadal stromal tumor
gastrointestinal stromal tumor, mastocytosis, seminoma
neuroendocrine tumor
Chromosomes 3, 7, 17, and 9p21 bladder cancer[15]
Many types of carcinoma, some types of sarcoma
smooth 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, CD34
vascular sarcoma
Glial fibrillary acidic protein (GFAP) glioma (astrocytoma, ependymoma)
Gross cystic disease fluid protein (GCDFP-15) breast cancer, ovarian cancer, salivary gland cancer
melanoma, PEComa (for example angiomyolipoma), clear cell carcinoma, adrenocortical carcinoma
Human chorionic gonadotropin (hCG) gestational trophoblastic disease, germ cell tumor, choriocarcinoma
lymphoma, leukemia
sex 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)
rhabdomyosarcoma, small-blue-round-cell tumor
muscle-specific actin (MSA) myosarcoma (leiomyosarcoma, rhabdomyosarcoma)
neuroendocrine 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
melanoma, 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
neuroendocrine tumor
lymphoma, leukemia, lung cancer, prostate cancer[16]
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
colorectal cancer,[17] Breast cancer,[18] [19] renal cell carcinoma[20] lung cancer,[21] [22] pancreatic cancer,[23] esophageal cancer,[24] stomach cancer,cervical cancer,[25] ovarian cancer,[26]
sarcoma, renal cell carcinoma, endometrial cancer, lung carcinoma, lymphoma, leukemia, melanoma

Accuracy and specific use

The ideal tumor marker has the following characteristics:

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.

See also

Further reading

Notes and References

  1. 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 . en . 44 . 4 . 1575–1600 . 10.1007/s00261-018-1845-0 . 30498924 . 54046548 . 2366-0058.
  2. Web site: ScienceDirect.com Science, health and medical journals, full text articles and books. . 2024-02-15 . www.sciencedirect.com.
  3. Nagpal . Madhav . Singh . Shreya . Singh . Pranshu . Chauhan . Pallavi . Zaidi . Meesam Abbas . 2016 . Tumor markers: A diagnostic tool . National Journal of Maxillofacial Surgery . 7 . 1 . 17–20 . 10.4103/0975-5950.196135 . free . 0975-5950 . 5242068 . 28163473.
  4. Sharma . S. . 2009 . Tumor markers in clinical practice: General principles and guidelines . Indian Journal of Medical and Paediatric Oncology . 30 . 1 . 1–8 . 10.4103/0971-5851.56328 . free . 0971-5851 . 2902207 . 20668599.
  5. Hayes . D. F. . Bast . R. C. . Desch . C. E. . Fritsche . H. . Kemeny . N. E. . Jessup . J. M. . Locker . G. Y. . Macdonald . J. S. . Mennel . R. G. . Norton . L. . Ravdin . P. . Taube . S. . Winn . R. J. . 1996-10-16 . Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers . Journal of the National Cancer Institute . 88 . 20 . 1456–1466 . 10.1093/jnci/88.20.1456 . 0027-8874 . 8841020.
  6. 10.1002/1097-0142(19920315)69:6+<1578::AID-CNCR2820691312>3.0.CO;2-K . Molecular marker test standardization . 1992 . Koepke . John A. . Cancer . 69 . 1578–81 . 1540898 . 6 Suppl. 9157824 . free .
  7. Promoting Safe and Effective Genetic Testing in the United States genome.gov
  8. https://books.google.com/books?id=pobC8zHbWzwC&pg=PA746 Page 746
  9. 10.1093/annonc/mdl492 . CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: A combined analysis of seven International Breast Cancer Study Group trials . 2006 . Keshaviah . A . Dellapasqua . S . Rotmensz . N . Lindtner . J . Crivellari . D . Collins . J . Colleoni . M . Thurlimann . B . Mendiola . C . Aebi . S . Price . K. . Pagani . O . Simoncini . E . Castiglione Gertsch . M . Gelber . R. . Coates . A. . Goldhirsch . A . Annals of Oncology . 18 . 4 . 701–8 . 17237474. 8 . free .
  10. Gion . M. . Mione . R. . Leon . A. E. . Lüftner . D. . Molina . R. . Possinger . K. . Robertson . J. F. . February 2001 . CA27.29: a valuable marker for breast cancer management. A confirmatory multicentric study on 603 cases . European Journal of Cancer . 37 . 3 . 355–363 . 10.1016/s0959-8049(00)00396-8 . 0959-8049 . 11239757.
  11. Lee . Tsinrong . Teng . Thomas Zheng Jie . Shelat . Vishal G . 2020-12-27 . Carbohydrate antigen 19-9 — tumor marker: Past, present, and future . World Journal of Gastrointestinal Surgery . 12 . 12 . 468–490 . 10.4240/wjgs.v12.i12.468 . free . 1948-9366 . 7769746 . 33437400.
  12. Osman N, O'Leary N, Mulcahy E, Barrett N, Wallis F, Hickey K, Gupta R . Correlation of serum CA125 with stage, grade and survival of patients with epithelial ovarian cancer at a single centre . Ir Med J . 101 . 8 . 245–7 . September 2008 . 18990955 .
  13. Bast RC, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB . CA 125: the past and the future . Int. J. Biol. Markers . 13 . 4 . 179–87 . 1998 . 10228898 . 10.1177/172460089801300402. 46589946 .
  14. Kudo . Takumi . Miyauchi . Akira . Ito . Yasuhiro . Yabuta . Tomonori . Inoue . Hiroyuki . Higashiyama . Takuya . Tomoda . Chisato . Hirokawa . Mitsuhide . Amino . Nobuyuki . 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 . 58 . 3 . 217–221 . 10.1507/endocrj.k10e-359 . 1348-4540 . 21358115.
  15. KE . ZUNFU . LAI . YUANHUA . MA . XUDONG . LIL . SHUHUA . HUANG . WENHUA . February 2014 . Diagnosis of bladder cancer from the voided urine specimens using multi-target fluorescence in situ hybridization . Oncology Letters . 7 . 2 . 325–330 . 10.3892/ol.2013.1744 . 1792-1074 . 3881196 . 24396440.
  16. Hallek . M. . Wanders . L. . Strohmeyer . S. . Emmerich . B. . 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 . 65 . 1 . 1–5 . 10.1007/BF01715117 . 0939-5555 . 1643153. 2748430 .
  17. 10.1038/sj.bjc.6603712 . Tumour M2-PK as a stool marker for colorectal cancer: Comparative analysis in a large sample of unselected older adults vs colorectal cancer patients . 2007 . Haug . U . Rothenbacher . D . Wente . M N . Seiler . C M . Stegmaier . C . Brenner . H . British Journal of Cancer . 17406361 . 2360192 . 96 . 9 . 1329–34.
  18. 11326672 . 2000 . Lüftner . D . Mesterharm . J . Akrivakis . C . Geppert . R . Petrides . PE . Wernecke . KD . Possinger . K . Tumor type M2 pyruvate kinase expression in advanced breast cancer . 20 . 6D . 5077–82 . Anticancer Research.
  19. 20592362 . 2010 . Benesch . C . Schneider . C . Voelker . HU . Kapp . M . Caffier . H . Krockenberger . M . Dietl . J . Kammerer . U . Schmidt . M . The clinicopathological and prognostic relevance of pyruvate kinase M2 and pAkt expression in breast cancer . 30 . 5 . 1689–94 . Anticancer Research .
  20. 10470199 . 1999 . Wechsel . HW . Petri . E . Bichler . KH . Feil . G . Marker for renal cell carcinoma (RCC): The dimeric form of pyruvate kinase type M2 (Tu M2-PK) . 19 . 4A . 2583–90 . Anticancer Research.
  21. 12624710 . 2003 . Schneider . J . Peltri . G . Bitterlich . N . Philipp . M . Velcovsky . HG . Morr . H . Katz . N . Eigenbrodt . E . Fuzzy logic-based tumor marker profiles improved sensitivity of the detection of progression in small-cell lung cancer patients . 2 . 4 . 185–91 . 10.1007/s102380300005 . Clinical and Experimental Medicine. 11010291 .
  22. 17882813 . 2007 . Oremek . G . Kukshaĭte . R . Sapoutzis . N . Ziolkovski . P . The significance of TU M2-PK tumor marker for lung cancer diagnostics . 85 . 7 . 56–8 . Klinicheskaia Meditsina.
  23. 11326648 . 2000 . Hardt . PD . Ngoumou . BK . Rupp . J . Schnell-Kretschmer . H . Kloer . HU . Tumor M2-pyruvate kinase: A promising tumor marker in the diagnosis of gastro-intestinal cancer . 20 . 6D . 4965–8 . Anticancer Research.
  24. 10.1097/MEG.0b013e3280102f78 . 17301655 . Tumour M2-pyruvate kinase: A gastrointestinal cancer marker . 2007 . Kumar . Yogesh . Tapuria . Niteen . Kirmani . Naveed . Davidson . Brian R. . European Journal of Gastroenterology & Hepatology . 19 . 3 . 265–276. 2131366 .
  25. 15210041 . 2004 . Kaura . B . Bagga . R . Patel . FD . Evaluation of the Pyruvate Kinase isoenzyme tumor (Tu M2-PK) as a tumor marker for cervical carcinoma . 30 . 3 . 193–6 . 10.1111/j.1447-0756.2004.00187.x . The Journal of Obstetrics and Gynaecology Research. 31214841 .
  26. 17479666 . 2007 . Ahmed . AS . Dew . T . Lawton . FG . Papadopoulos . AJ . Devaja . O . Raju . KS . Sherwood . RA . M2-PK as a novel marker in ovarian cancer. A prospective cohort study . 28 . 2 . 83–8 . European Journal of Gynaecological Oncology.

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