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Tumor marker

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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.[2]

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.[2]

Classification

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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 They were previously widely used, but they have largely been replaced by oncofetal antigens and monoclonal antibodies, due to disadvantages such as most of them lacking organ specificity.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.[3]

Uses

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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.[4]

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.[5] The only approved diagnostic method for cancer is with a biopsy.

  • Detects reoccurring cancers

Tumor markers can detect reoccurring cancers in patients post-treatment.[4]

Techniques

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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.[2]

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.[6]

Interlaboratory proficiency testing for tumor marker tests, and for clinical tests more generally, is routine in Europe and an emerging field[7] in the United States. New York state is prominent in advocating such research.[8]

List of commonly used markers

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Tumor marker Associated tumor types
Alpha fetoprotein (AFP) germ cell tumor, hepatocellular carcinoma[9]
CA15-3 breast cancer[10]
CA27.29 breast cancer[11]
CA19-9 Mainly pancreatic cancer, but also colorectal cancer and other types of gastrointestinal cancer.[12]
CA-125 Mainly ovarian cancer,[13] but may also be elevated in for example endometrial cancer, fallopian tube cancer, lung cancer, breast cancer and gastrointestinal cancer.[14]
Calcitonin medullary thyroid carcinoma[15]
Calretinin mesothelioma, sex cord-gonadal stromal tumor, adrenocortical carcinoma, synovial sarcoma[9]
Carcinoembryonic antigen (CEA) gastrointestinal cancer, cervix cancer, lung cancer, ovarian cancer, breast cancer, urinary tract cancer[9]
CD34 hemangiopericytoma/solitary fibrous tumor, pleomorphic lipoma, gastrointestinal stromal tumor, dermatofibrosarcoma protuberans[9]
CD99 Ewing sarcoma, primitive neuroectodermal tumor, hemangiopericytoma/solitary fibrous tumor, synovial sarcoma, lymphoma, leukemia, sex cord-gonadal stromal tumor[9]
CD117 gastrointestinal stromal tumor, mastocytosis, seminoma[9]
Chromogranin neuroendocrine tumor[9]
Chromosomes 3, 7, 17, and 9p21 bladder cancer[16]
Cytokeratin Many types of carcinoma, some types of sarcoma[9]
Desmin smooth muscle sarcoma, skeletal muscle sarcoma, endometrial stromal sarcoma[9]
Epithelial membrane antigen (EMA) many types of carcinoma, meningioma, some types of sarcoma[9]
Factor VIII; CD31, FL1, CD34 vascular sarcoma[9]
Glial fibrillary acidic protein (GFAP) glioma (astrocytoma, ependymoma)[9]
Gross cystic disease fluid protein (GCDFP-15) breast cancer, ovarian cancer, salivary gland cancer[9]
HMB-45 melanoma, PEComa (for example angiomyolipoma), clear cell carcinoma, adrenocortical carcinoma[9]
Human chorionic gonadotropin (hCG) gestational trophoblastic disease, germ cell tumor, choriocarcinoma[9]
immunoglobulin lymphoma, leukemia[9]
inhibin sex cord-gonadal stromal tumor, adrenocortical carcinoma, hemangioblastoma[9]
keratin (various types) carcinoma, some types of sarcoma[9]
lymphocyte marker (various types) lymphoma, leukemia[9]
MART-1 (Melan-A) melanoma, steroid-producing tumors (adrenocortical carcinoma, gonadal tumor)[9]
Myo D1 rhabdomyosarcoma, small-blue-round-cell tumor[9]
muscle-specific actin (MSA) myosarcoma (leiomyosarcoma, rhabdomyosarcoma)[9]
neurofilament neuroendocrine tumor; small-cell carcinoma of the lung[9]
neuron-specific enolase (NSE) neuroendocrine tumor; small-cell carcinoma of the lung, breast cancer[9]
placental alkaline phosphatase (PLAP) seminoma, dysgerminoma, embryonal carcinoma[9]
prostate-specific antigen (PSA) prostate[9]
S100 protein melanoma, sarcoma (neurosarcoma, lipoma, chondrosarcoma), astrocytoma, gastrointestinal stromal tumor, salivary gland cancer, some types of adenocarcinoma, histiocytic tumor (dendritic cell, macrophage)[9]
smooth muscle actin (SMA) gastrointestinal stromal tumor, leiomyosarcoma, PEComa[9]
synaptophysin neuroendocrine tumor[9]
thymidine kinase lymphoma, leukemia, lung cancer, prostate cancer[17]
thyroglobulin (Tg) post-operative marker of thyroid cancer (but not in medullary thyroid cancer)[9]
thyroid transcription factor-1 (TTF-1) all types of thyroid cancer, lung cancer[9]
Tumor M2-PK colorectal cancer,[18] Breast cancer,[19][20] renal cell carcinoma[21] lung cancer,[22][23] pancreatic cancer,[24] esophageal cancer,[25] stomach cancer,[25]cervical cancer,[26] ovarian cancer,[27]
vimentin sarcoma, renal cell carcinoma, endometrial cancer, lung carcinoma, lymphoma, leukemia, melanoma[9]

Accuracy and specific use

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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.[5]

See also

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References

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  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. 44 (4): 1575–1600. doi:10.1007/s00261-018-1845-0. ISSN 2366-0058. PMID 30498924. S2CID 54046548.
  2. ^ a b c Sokoll, Lori J.; Chan, Daniel W. (2020-01-01), "Tumor markers", Contemporary Practice in Clinical Chemistry, Academic Press, pp. 779–793, doi:10.1016/B978-0-12-815499-1.00044-2, ISBN 978-0-12-815499-1, S2CID 263459844, retrieved 2024-02-15
  3. ^ "ScienceDirect.com | Science, health and medical journals, full text articles and books". www.sciencedirect.com. Retrieved 2024-02-15.
  4. ^ a b 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. doi:10.4103/0975-5950.196135. ISSN 0975-5950. PMC 5242068. PMID 28163473.
  5. ^ a b Sharma, S. (2009). "Tumor markers in clinical practice: General principles and guidelines". Indian Journal of Medical and Paediatric Oncology. 30 (1): 1–8. doi:10.4103/0971-5851.56328. ISSN 0971-5851. PMC 2902207. PMID 20668599.
  6. ^ 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. doi:10.1093/jnci/88.20.1456. ISSN 0027-8874. PMID 8841020.
  7. ^ Koepke, John A. (1992). "Molecular marker test standardization". Cancer. 69 (6 Suppl): 1578–81. doi:10.1002/1097-0142(19920315)69:6+<1578::AID-CNCR2820691312>3.0.CO;2-K. PMID 1540898. S2CID 9157824.
  8. ^ Promoting Safe and Effective Genetic Testing in the United States genome.gov
  9. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af Page 746 in: Title Manual of clinical oncology Spiral manual Manual of Clinical Oncology Lippincott Manual Series Authors Dennis Albert Casciato, Mary C. Territo Editors Dennis Albert Casciato, Mary C. Territo Contributor Mary C. Territo Edition 6, illustrated Publisher Lippincott Williams & Wilkins, 2008 ISBN 0-7817-6884-5, ISBN 978-0-7817-6884-9
  10. ^ Keshaviah, A; Dellapasqua, S; Rotmensz, N; Lindtner, J; Crivellari, D; Collins, J; Colleoni, M; Thurlimann, B; et al. (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. 18 (4): 701–8. doi:10.1093/annonc/mdl492. PMID 17237474.
  11. ^ 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. doi:10.1016/s0959-8049(00)00396-8. ISSN 0959-8049. PMID 11239757.
  12. ^ 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. doi:10.4240/wjgs.v12.i12.468. ISSN 1948-9366. PMC 7769746. PMID 33437400.
  13. ^ Osman N, O'Leary N, Mulcahy E, Barrett N, Wallis F, Hickey K, Gupta R (September 2008). "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. PMID 18990955.
  14. ^ Bast RC, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB (1998). "CA 125: the past and the future". Int. J. Biol. Markers. 13 (4): 179–87. doi:10.1177/172460089801300402. PMID 10228898. S2CID 46589946.
  15. ^ 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. doi:10.1507/endocrj.k10e-359. ISSN 1348-4540. PMID 21358115.
  16. ^ 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. doi:10.3892/ol.2013.1744. ISSN 1792-1074. PMC 3881196. PMID 24396440.
  17. ^ 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. doi:10.1007/BF01715117. ISSN 0939-5555. PMID 1643153. S2CID 2748430.
  18. ^ Haug, U; Rothenbacher, D; Wente, M N; Seiler, C M; Stegmaier, C; Brenner, H (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. 96 (9): 1329–34. doi:10.1038/sj.bjc.6603712. PMC 2360192. PMID 17406361.
  19. ^ Lüftner, D; Mesterharm, J; Akrivakis, C; Geppert, R; Petrides, PE; Wernecke, KD; Possinger, K (2000). "Tumor type M2 pyruvate kinase expression in advanced breast cancer". Anticancer Research. 20 (6D): 5077–82. PMID 11326672.
  20. ^ Benesch, C; Schneider, C; Voelker, HU; Kapp, M; Caffier, H; Krockenberger, M; Dietl, J; Kammerer, U; Schmidt, M (2010). "The clinicopathological and prognostic relevance of pyruvate kinase M2 and pAkt expression in breast cancer". Anticancer Research. 30 (5): 1689–94. PMID 20592362.
  21. ^ Wechsel, HW; Petri, E; Bichler, KH; Feil, G (1999). "Marker for renal cell carcinoma (RCC): The dimeric form of pyruvate kinase type M2 (Tu M2-PK)". Anticancer Research. 19 (4A): 2583–90. PMID 10470199.
  22. ^ Schneider, J; Peltri, G; Bitterlich, N; Philipp, M; Velcovsky, HG; Morr, H; Katz, N; Eigenbrodt, E (2003). "Fuzzy logic-based tumor marker profiles improved sensitivity of the detection of progression in small-cell lung cancer patients". Clinical and Experimental Medicine. 2 (4): 185–91. doi:10.1007/s102380300005. PMID 12624710. S2CID 11010291.
  23. ^ Oremek, G; Kukshaĭte, R; Sapoutzis, N; Ziolkovski, P (2007). "The significance of TU M2-PK tumor marker for lung cancer diagnostics". Klinicheskaia Meditsina. 85 (7): 56–8. PMID 17882813.
  24. ^ Hardt, PD; Ngoumou, BK; Rupp, J; Schnell-Kretschmer, H; Kloer, HU (2000). "Tumor M2-pyruvate kinase: A promising tumor marker in the diagnosis of gastro-intestinal cancer". Anticancer Research. 20 (6D): 4965–8. PMID 11326648.
  25. ^ a b Kumar, Yogesh; Tapuria, Niteen; Kirmani, Naveed; Davidson, Brian R. (2007). "Tumour M2-pyruvate kinase: A gastrointestinal cancer marker". European Journal of Gastroenterology & Hepatology. 19 (3): 265–276. doi:10.1097/MEG.0b013e3280102f78. PMID 17301655. S2CID 2131366.
  26. ^ Kaura, B; Bagga, R; Patel, FD (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. 30 (3): 193–6. doi:10.1111/j.1447-0756.2004.00187.x. PMID 15210041. S2CID 31214841.
  27. ^ Ahmed, AS; Dew, T; Lawton, FG; Papadopoulos, AJ; Devaja, O; Raju, KS; Sherwood, RA (2007). "M2-PK as a novel marker in ovarian cancer. A prospective cohort study". European Journal of Gynaecological Oncology. 28 (2): 83–8. PMID 17479666.

Further reading

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  • Lüftner, D; Mesterharm, J; Akrivakis, C; Geppert, R; Petrides, PE; Wernecke, KD; Possinger, K (2000). "Tumor type M2 pyruvate kinase expression in advanced breast cancer". Anticancer Research. 20 (6D): 5077–82. PMID 11326672.
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