Tumor marker

Last updated

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]

Contents

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

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 They were previously widely used, but they have largely been replaced by oncofetal antigens and monoclonal antibodies, due to disadvantages such as most of them lacking organ specificity.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

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. [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).

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.

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

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. [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

Tumor markerAssociated 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

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. [5]

See also

Related Research Articles

<span class="mw-page-title-main">Radiation therapy</span> Therapy using ionizing radiation, usually to treat cancer

Radiation therapy or radiotherapy is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle accelerator. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body, and have not spread to other parts. It may also be used as part of adjuvant therapy, to prevent tumor recurrence after surgery to remove a primary malignant tumor. Radiation therapy is synergistic with chemotherapy, and has been used before, during, and after chemotherapy in susceptible cancers. The subspecialty of oncology concerned with radiotherapy is called radiation oncology. A physician who practices in this subspecialty is a radiation oncologist.

<span class="mw-page-title-main">Biopsy</span> Medical test involving extraction of sample cells or tissues for examination

A biopsy is a medical test commonly performed by a surgeon, an interventional radiologist, or an interventional cardiologist. The process involves the extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is then fixed, dehydrated, embedded, sectioned, stained and mounted before it is generally examined under a microscope by a pathologist; it may also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous or inflammatory conditions.

<span class="mw-page-title-main">Chronic lymphocytic leukemia</span> Medical condition

Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes. Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur. Enlargement of the spleen and low red blood cells (anemia) may also occur. It typically worsens gradually over years.

<span class="mw-page-title-main">Malignancy</span> Tendency of a medical condition to become progressively worse

Malignancy is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer.

<span class="mw-page-title-main">Gastrointestinal stromal tumor</span> Human disease (cancer)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior is driven by mutations in the KIT gene (85%), PDGFRA gene (10%), or BRAF kinase (rare). 95% of GISTs stain positively for KIT (CD117). Most (66%) occur in the stomach and gastric GISTs have a lower malignant potential than tumors found elsewhere in the GI tract.

A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

<span class="mw-page-title-main">Thymidine kinase</span> Enzyme found in most living cells

Thymidine kinase is an enzyme, a phosphotransferase : 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, EC 2.7.1.21. It can be found in most living cells. It is present in two forms in mammalian cells, TK1 and TK2. Certain viruses also have genetic information for expression of viral thymidine kinases. Thymidine kinase catalyzes the reaction:

<span class="mw-page-title-main">Carcinoembryonic antigen</span> Glycoprotein secreted into the luminal surface of the epithelia in the gastrointestinal tract

Carcinoembryonic antigen (CEA) describes a set of highly-related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is usually present at very low levels in the blood of healthy adults. However, the serum levels are raised in some types of cancer, which means that it can be used as a tumor marker in clinical tests. Serum levels can also be elevated in heavy smokers.

In oncology, the Warburg effect is the observation that most cancer cells release energy predominantly not through the 'usual' citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of a high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The precise mechanism and therapeutic implications of the Warburg effect, however, remain unclear.

Tumor M2-PK is a synonym for the dimeric form of the pyruvate kinase isoenzyme type M2 (PKM2), a key enzyme within tumor metabolism. Tumor M2-PK can be elevated in many tumor types, rather than being an organ-specific tumor marker such as PSA. Increased stool (fecal) levels are being investigated as a method of screening for colorectal tumors, and EDTA plasma levels are undergoing testing for possible application in the follow-up of various cancers.

<span class="mw-page-title-main">40S ribosomal protein S27</span> Protein found in humans

40S ribosomal protein S27, also known as metallopan-stimulin 1 or MPS-1, is a protein that in humans is encoded by the RPS27 gene. Metallopanstimulin is a zinc finger protein proposed to be involved DNA repair as well as oncogenesis.

<span class="mw-page-title-main">Epithelioid sarcoma</span> Medical condition

Epithelioid sarcoma is a rare soft tissue sarcoma arising from mesenchymal tissue and characterized by epithelioid-like features. It accounts for less than 1% of all soft tissue sarcomas. It was first definitively characterized by F.M. Enzinger in 1970. It commonly presents itself in the distal limbs of young adults as a small, soft mass or a cluster of bumps. A proximal version has also been described, frequently occurring in the upper extremities. Less commonly, cases are reported in the pelvis, vulva, penis, and spine.

Proliferation, as one of the hallmarks and most fundamental biological processes in tumors, is associated with tumor progression, response to therapy, and cancer patient survival. Consequently, the evaluation of a tumor proliferative index has clinical significance in characterizing many solid tumors and hematologic malignancies. This has led investigators to develop different technologies to evaluate the proliferation index in tumor samples. The most commonly used methods in evaluating a proliferative index include mitotic indexing, thymidine-labeling index, bromodeoxyuridine assay, the determination of fraction of cells in various phases of cell cycle, and the immunohistochemical evaluation of cell cycle-associated proteins.

A circulating tumor cell (CTC) is a cell that has shed into the vasculature or lymphatics from a primary tumor and is carried around the body in the blood circulation. CTCs can extravasate and become seeds for the subsequent growth of additional tumors (metastases) in distant organs, a mechanism that is responsible for the vast majority of cancer-related deaths. The detection and analysis of CTCs can assist early patient prognoses and determine appropriate tailored treatments. Currently, there is one FDA-approved method for CTC detection, CellSearch, which is used to diagnose breast, colorectal and prostate cancer.

<span class="mw-page-title-main">PCA3</span> Non-coding RNA in the species Homo sapiens

Prostate cancer antigen 3 is a gene that expresses a non-coding RNA. PCA3 is only expressed in human prostate tissue, and the gene is highly overexpressed in prostate cancer. Because of its restricted expression profile, the PCA3 RNA is useful as a tumor marker.

<span class="mw-page-title-main">Oncology</span> Branch of medicine dealing with, or specializing in, cancer

Oncology is a branch of medicine that deals with the study, treatment, diagnosis, and prevention of cancer. A medical professional who practices oncology is an oncologist. The name's etymological origin is the Greek word ὄγκος (ónkos), meaning "tumor", "volume" or "mass". Oncology is concerned with:

<span class="mw-page-title-main">Follicular dendritic cell sarcoma</span> Dendritic cell sarcoma cancer that effects the follicular dendritic cells

Follicular dendritic cell sarcoma (FDCS) is an extremely rare neoplasm. While the existence of FDC tumors was predicted by Lennert in 1978, the tumor wasn't fully recognized as its own cancer until 1986 after characterization by Monda et al. It accounts for only 0.4% of soft tissue sarcomas, but has significant recurrent and metastatic potential and is considered an intermediate grade malignancy. The major hurdle in treating FDCS has been misdiagnosis. It is a newly characterized cancer, and because of its similarities in presentation and markers to lymphoma, both Hodgkin and Non-Hodgkin subtypes, diagnosis of FDCS can be difficult. With recent advancements in cancer biology better diagnostic assays and chemotherapeutic agents have been made to more accurately diagnose and treat FDCS.

<span class="mw-page-title-main">Cancer biomarker</span> Substance or process that is indicative of the presence of cancer in the body

A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. Ideally, such biomarkers can be assayed in non-invasively collected biofluids like blood or serum.

mTOR inhibitors Class of pharmaceutical drugs

mTOR inhibitors are a class of drugs that inhibit the mammalian target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. The most established mTOR inhibitors are so-called rapalogs, which have shown tumor responses in clinical trials against various tumor types.

Thymidine kinase is an enzyme, a phosphotransferase : 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, EC 2.7.1.21 that catalyzes the reaction:

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. 44 (4): 1575–1600. doi:10.1007/s00261-018-1845-0. ISSN   2366-0058. PMID   30498924. S2CID   54046548.
  2. 1 2 3 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. 1 2 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. 1 2 Sharma, S. (2009). "Tumor markers in clinical practice: General principles and guidelines". Indian Journal of Medical and Paediatric Oncology : Official Journal of Indian Society of Medical & 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. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 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 (Oxford, England: 1990). 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. 1 2 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