Tumor markers

A tumor marker is a substance 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.

Contents   [hide]  1 Uses 2 Techniques 3 Examples 4 Sources of inaccuracy 5 See also 6 References 7 Further reading 8 External links

[edit]Uses

Uses of tumor markers can broadly be classified as follows:^[1]

• Screening for common cancers on a population basis. Example: elevated prostate specific antigen suggests prostate cancer.
• Monitoring of cancer survivors after treatment. Example: elevated AFP in a child previously treated for teratoma suggests relapse with endodermal sinus tumor.
• Diagnosis of specific tumor types, particularly in certain brain tumors and other instances where biopsy is not feasible.

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.^[2] 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.^[3]

[edit]Techniques

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.^[1]In the United States, New York state is prominent in advocating such research.^[4]

[edit]Examples

Tumor marker	Associated tumor types
Alpha fetoprotein (AFP)	germ cell tumor, hepatocellular carcinoma[5]
CA15-3	breast cancer[6]
CA27-29	breast cancer
CA19-9	Mainly pancreatic cancer, but also colorectal cancer and other types of gastrointestinal cancer.[7]
CA-125	Mainly ovarian cancer,[8] but may also be elevated in for example endometrial cancer, fallopian tube cancer, lung cancer, breast cancer andgastrointestinal cancer.[9] May also increase in endometriosis.[10]
Calretinin	mesothelioma, sex cord-gonadal stromal tumour, adrenocortical carcinoma, synovial sarcoma[5]
Carcinoembryonic antigen	gastrointestinal cancer, cervix cancer, lung cancer, ovarian cancer, breast cancer, urinary tract cancer[5]
CD34	hemangiopericytoma/solitary fibrous tumor, pleomorphic lipoma, gastrointestinal stromal tumor, dermatofibrosarcoma protuberans[5]
CD99	Ewing sarcoma, primitive neuroectodermal tumor, hemangiopericytoma/solitary fibrous tumor, synovial sarcoma, lymphoma, leukemia, sex cord-gonadal stromal tumour[5]
CD117	gastrointestinal stromal tumor, mastocytosis, seminoma[5]
Chromogranin	neuroendocrine tumor[5]
Cytokeratin (various types)	Many types of carcinoma, some types of sarcoma[5]
Desmin	smooth muscle sarcoma, skeletal muscle sarcoma, endometrial stromal sarcoma[5]
Epithelial membrane protein(EMA)	many types of carcinoma, meningioma, some types of sarcoma[5]
Factor VIII, CD31 FL1	vascular sarcoma[5]
Glial fibrillary acidic protein(GFAP)	glioma (astrocytoma, ependymoma)[5]
Gross cystic disease fluid protein (GCDFP-15)	breast cancer, ovarian cancer, salivary gland cancer[5]
HMB-45	melanoma, PEComa (for example angiomyolipoma), clear cell carcinoma, adrenocortical carcinoma[5]
Human chorionic gonadotropin(hCG)	gestational trophoblastic disease, germ cell tumor, choriocarcinoma[5]
immunoglobulin	lymphoma, leukemia[5]
inhibin	sex cord-gonadal stromal tumour, adrenocortical carcinoma, hemangioblastoma[5]
keratin (various types)	carcinoma, some types of sarcoma[5]
PTPRC (CD45)	lymphoma, leukemia, histiocytic tumor[5]
lymphocyte marker (various types	lymphoma, leukemia[5]
MART-1 (Melan-A)	melanoma, steroid-producing tumors (adrenocortical carcinoma, gonadal tumor)[5]
Myo D1	rhabdomyosarcoma, small, round, blue cell tumour[5]
muscle-specific actin (MSA)	myosarcoma (leiomyosarcoma, rhabdomyosarcoma)[5]
neurofilament	neuroendocrine tumor, small-cell carcinoma of the lung[5]
neuron-specific enolase (NSE)	neuroendocrine tumor, small-cell carcinoma of the lung, breast cancer[5]
placental alkaline phosphatase(PLAP)	seminoma, dysgerminoma, embryonal carcinoma[5]
prostate-specific antigen	prostate[5]
S100 protein	melanoma, sarcoma (neurosarcoma, lipoma, chondrosarcoma), astrocytoma, gastrointestinal stromal tumor, salivary gland cancer, some types ofadenocarcinoma, histiocytic tumor (dendritic cell, macrophage)[5]
smooth muscle actin (SMA)	gastrointestinal stromal tumor, leiomyosarcoma, PEComa[5]
synaptophysin	neuroendocrine tumor[5]
thyroglobulin	thyroid cancer (but not in medullary thyroid cancer)[5]
thyroid transcription factor-1	all types of thyroid cancer, lung cancer[5]
Tumor M2-PK	colorectal cancer,[11] Breast cancer,[12][13] renal cell carcinoma[14][15] Lung cancer,[16][17] Pancreatic cancer,[18] Esophageal Cancer,[19] Stomach Cancer,[19]Cervical Cancer,[20] Ovarian Cancer,[21]
vimentin	sarcoma, renal cell carcinoma, endometrial cancer, lung carcinoma, lymphoma, leukemia, melanoma[5]

[edit]Sources of inaccuracy

The high dose hook effect is an artefact 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.^[22] 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.

[edit]See also

• Tumor antigen
• List of cancer types

[edit]References

1. ^ ^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.
2. ^ Kilpatrick, E. S; Lind, M. J (2009). "Appropriate requesting of serum tumour markers".BMJ 339: b3111. doi:10.1136/bmj.b3111. PMID 19773324.
3. ^ 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.
4. ^ Promoting Safe and Effective Genetic Testing in the United States genome.gov
5. ^ ^{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
6. ^ 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.
7. ^ gpnotebook.co.uk > ca-19-9 Retrieved November 2011
8. ^ 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.
9. ^ 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.
10. ^ 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.
11. ^ 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.
12. ^ 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.
13. ^ Benesch, C; Schneider, C; Voelker, HU; Kapp, M; Caffier, H; Krockenberger, M; Dietl, J; Kammerer, U et al. (2010). "The clinicopathological and prognostic relevance of pyruvate kinase M2 and pAkt expression in breast cancer". Anticancer research 30 (5): 1689–94. PMID 20592362.
14. ^ 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.
15. ^ 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 research19 (4A): 2583–90. PMID 10470199.
16. ^ 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.
17. ^ 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.
18. ^ 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.
19. ^ ^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.
20. ^ 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.
21. ^ 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.
22. ^ Leboeuf, R. (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.