Tumor marker

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A tumor marker is a biomarker found in the blood, urine, or body tissues that can be elevated in cancer, among other tissue types. There are many different tumor markers, each indicative of a particular disease process, and they are used in oncology to help detect the presence of cancer. An elevated level of a tumor marker can indicate cancer; however, there can also be other causes of the elevation.

Tumor markers can be produced directly by the tumor or by non-tumor cells as a response to the presence of a tumor. Most tumor markers are tumor antigens, but not all tumor antigens can be used as tumor markers.[clarification needed][citation needed]

Although mammography, ultrasonography, computed tomography, magnetic resonance imaging scans, and tumor marker assays help in the staging and treatment of the cancer, they are usually not definitive diagnostic tests. The diagnosis is confirmed by biopsy.[1]


On the basis of chemical nature tumor markers can be divided into:

  • Protein
  • Antigen
  • Enzyme
  • Hormone
  • Carbohydrate


Uses of tumor markers can broadly be classified as follows:[2]

As stated in the BMJ 2009, tumour markers should not generally be used for the purpose of diagnosis of cancers, as opposed to monitoring purposes in certain cancers, or in certain cases, screening purposes.[3] The use of these tests without understanding their utility has resulted in inappropriate use of tumour marker blood tests, which has also resulted in further inappropriate over-investigation for cancers.[4]


Tumor markers can be detected by immunohistochemistry.

If repeated measurements of tumor marker are needed, some clinical testing laboratories provide a special reporting mechanism, a serial monitor, that links test results and other data pertaining to the person being tested. This requires a unique identifier for the person. In the United States commonly a Social Security number & Civil Personal Record (CPR) in Bahrain are used for this. One important function of this mechanism is to ensure that each test is performed using the same assay kit. For example, for AFP many different commercial assay kits, based on different technologies, are available. AFP measurements obtained using different assay kits are not comparable unless special calculations are performed.

Interlaboratory proficiency testing for tumor marker tests, and for clinical tests more generally, is an emerging field.[2] In the United States, New York state is prominent in advocating such research.[5]


Tumor marker Associated tumor types
Alpha fetoprotein (AFP) germ cell tumor, hepatocellular carcinoma[6]
CA15-3 breast cancer[7]
CA27-29 breast cancer[8]
CA19-9 Mainly pancreatic cancer, but also colorectal cancer and other types of gastrointestinal cancer.[9]
CA-125 Mainly ovarian cancer,[10] but may also be elevated in for example endometrial cancer, fallopian tube cancer, lung cancer, breast cancer and gastrointestinal cancer.[11] May also increase in endometriosis.[12]
Calcitonin medullary thyroid carcinoma
Calretinin mesothelioma, sex cord-gonadal stromal tumour, adrenocortical carcinoma, synovial sarcoma[6]
Carcinoembryonic antigen gastrointestinal cancer, cervix cancer, lung cancer, ovarian cancer, breast cancer, urinary tract cancer[6]
CD34 hemangiopericytoma/solitary fibrous tumor, pleomorphic lipoma, gastrointestinal stromal tumor, dermatofibrosarcoma protuberans[6]
CD99MIC 2 Ewing sarcoma, primitive neuroectodermal tumor, hemangiopericytoma/solitary fibrous tumor, synovial sarcoma, lymphoma, leukemia, sex cord-gonadal stromal tumour[6]
CD117 gastrointestinal stromal tumor, mastocytosis, seminoma[6]
Chromogranin neuroendocrine tumor[6]
Chromosomes 3, 7, 17, and 9p21 bladder cancer[13]
Cytokeratin (various types) Many types of carcinoma, some types of sarcoma[6]
Desmin smooth muscle sarcoma, skeletal muscle sarcoma, endometrial stromal sarcoma[6]
Epithelial membrane antigen (EMA) many types of carcinoma, meningioma, some types of sarcoma[6]
Factor VIII, CD31 FL1 vascular sarcoma[6]
Glial fibrillary acidic protein (GFAP) glioma (astrocytoma, ependymoma)[6]
Gross cystic disease fluid protein (GCDFP-15) breast cancer, ovarian cancer, salivary gland cancer[6]
HMB-45 melanoma, PEComa (for example angiomyolipoma), clear cell carcinoma, adrenocortical carcinoma[6]
Human chorionic gonadotropin (hCG) gestational trophoblastic disease, germ cell tumor, choriocarcinoma[6]
immunoglobulin lymphoma, leukemia[6]
inhibin sex cord-gonadal stromal tumour, adrenocortical carcinoma, hemangioblastoma[6]
keratin (various types) carcinoma, some types of sarcoma[6]
lymphocyte marker (various types lymphoma, leukemia[6]
MART-1 (Melan-A) melanoma, steroid-producing tumors (adrenocortical carcinoma, gonadal tumor)[6]
Myo D1 rhabdomyosarcoma, small, round, blue cell tumour[6]
muscle-specific actin (MSA) myosarcoma (leiomyosarcoma, rhabdomyosarcoma)[6]
neurofilament neuroendocrine tumor, small-cell carcinoma of the lung[6]
neuron-specific enolase (NSE) neuroendocrine tumor, small-cell carcinoma of the lung, breast cancer[6]
placental alkaline phosphatase (PLAP) seminoma, dysgerminoma, embryonal carcinoma[6]
prostate-specific antigen prostate[6]
PTPRC (CD45) lymphoma, leukemia, histiocytic tumor[6]
S100 protein melanoma, sarcoma (neurosarcoma, lipoma, chondrosarcoma), astrocytoma, gastrointestinal stromal tumor, salivary gland cancer, some types of adenocarcinoma, histiocytic tumor (dendritic cell, macrophage)[6]
smooth muscle actin (SMA) gastrointestinal stromal tumor, leiomyosarcoma, PEComa[6]
synaptophysin neuroendocrine tumor[6]
thyroglobulin post-operative marker of thyroid cancer (but not in medullary thyroid cancer)[6]
thyroid transcription factor-1 all types of thyroid cancer, lung cancer[6]
Tumor M2-PK colorectal cancer,[14] Breast cancer,[15][16] renal cell carcinoma[17][18] Lung cancer,[19][20] Pancreatic cancer,[21] Esophageal Cancer,[22] Stomach Cancer,[22]Cervical Cancer,[23] Ovarian Cancer,[24]
vimentin sarcoma, renal cell carcinoma, endometrial cancer, lung carcinoma, lymphoma, leukemia, melanoma[6]

Sources of inaccuracy[edit]

The high dose hook effect is an artifact of tumor marker immunoassay kits, that causes the reported quantity of tumor marker to be incorrectly low when the quantity is high. An undetected hook effect may cause delayed recognition of a tumor.[25] The hook effect can be detected by analyzing serial dilutions. The hook effect is absent if the reported quantities of tumor marker in a serial dilution are proportional to the dilution.

Multiple Tumor marker test[edit]

As with other diagnostic tests, tumor markers have a few test characteristics that influence their usability:

  • Imperfect sensitivity, which would result in false negative tests. I.e. the test result is reassuring but cancer is present or has recurred, progressed...
  • Imperfect specificity, resulting in false positive tests. I.e. no cancer is present but the test result indicates the opposite, resulting in needless further testing or anxiety.

As with other tests, predictive value (the chance that a positive or negative result represents the truth), depends strongly on the pre-test probability. For example, in a population where very few people in a population have active cancer, it might be unusual to be healthy and have a wrong test result - but it is far unusual still to have cancer, thus most people with positive test results do not have cancer. This is why many tumor markers are not, by and large, useful diagnostic tests, but more often useful to find the origin of confirmed carcinoma of unknown primary or to track the evolution of a confirmed tumor.

Multiple Tumor marker tests will give a more exact result; these are:[1]

  • Colorectal: M2-PK, if M2-PK is not available, so can test CEA, CA 19-9, CA 125
  • Breast: CEA, CA 15-3, Cyfra 21-1
  • Ovary: CEA, CA 19-9, CA 125, AFP, BHCG
  • Uterine: CEA, CA 19-9, CA 125, Cyfra 21-1, SCC
  • Prostate: PSA, FPSA and ratio
  • Testicle: AFP, BHCG
  • Pancreas/Stomach: CEA, CA 19-9, CA 72-4
  • Liver: CEA, AFP
  • Oesophagus: CEA, Cyfra 21-1
  • Thyroid: CEA, NSE
  • Lung: CEA, CA 19-9, CA 125, NSE, Cyfra 21-1 (Sensitivity at 95 percent percentile for Cyfra 21-1 is 79 percent, while for SCC and CEA are 41 and 31 percent respectively)[26]
  • Bladder: CEA, Cyfra 21-1, TPA

See also[edit]


  1. ^ a b "Tumor markers Cancer screening". Retrieved December 28, 2013. 
  2. ^ a b 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. 
  3. ^ Kilpatrick, E. S; Lind, M. J (2009). "Appropriate requesting of serum tumour markers". BMJ 339: b3111. doi:10.1136/bmj.b3111. PMID 19773324. 
  4. ^ Krishnan, S T M; Philipose, Z; Rayman, G (2002). "Lesson of the week: Hypothyroidism mimicking intra-abdominal malignancy". BMJ 325 (7370): 946–7. doi:10.1136/bmj.325.7370.946. PMC 1124444. PMID 12399347. 
  5. ^ Promoting Safe and Effective Genetic Testing in the United States genome.gov
  6. ^ 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 ag 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
  7. ^ 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. 
  8. ^ "Definition of CA 27-29. From MedicineNet. Last Editorial Review: 6/14/2012". 
  9. ^ gpnotebook.co.uk > ca-19-9 Retrieved November 2011
  10. ^ 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. 
  11. ^ 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. PMID 10228898. 
  12. ^ Bagan P, Berna P, Assouad J, Hupertan V, Le Pimpec Barthes F, Riquet M (January 2008). "Value of cancer antigen 125 for diagnosis of pleural endometriosis in females with recurrent pneumothorax". Eur. Respir. J. 31 (1): 140–2. doi:10.1183/09031936.00094206. PMID 17804443. 
  13. ^ "Tumor Markers". Retrieved June 6, 2013. 
  14. ^ 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. doi:10.1038/sj.bjc.6603712. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ Oremek, GM; Sapoutzis, N; Kramer, W; Bickeböller, R; Jonas, D (2000). "Value of tumor M2 (Tu M2-PK) in patients with renal carcinoma". Anticancer research 20 (6D): 5095–8. PMID 11326675. 
  18. ^ 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. 
  19. ^ 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. 
  20. ^ 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. 
  21. ^ 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. 
  22. ^ 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. doi:10.1097/MEG.0b013e3280102f78. 
  23. ^ 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. 
  24. ^ 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. 
  25. ^ Leboeuf, R.; Langlois, Marie-France; Martin, Marc; Ahnadi, Charaf E.; Fink, Guy D. (2005). ""Hook Effect" in Calcitonin Immunoradiometric Assay in Patients with Metastatic Medullary Thyroid Carcinoma: Case Report and Review of the Literature". Journal of Clinical Endocrinology & Metabolism 91 (2): 361. doi:10.1210/jc.2005-1429. 
  26. ^ "Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: a Bayesian analysis". Retrieved August 6, 2014. 

Further reading[edit]

  • 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. 

External links[edit]