# Tumor marker

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 They were previously widely used, but they have largely been replaced by oncofetal antigens and monoclonal antibodies, due to disadvantages such as most of them lacking organ specificity.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

## Uses

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.
* Screening for cancers
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. The only approved diagnostic method for cancer is with a biopsy.
* Detects reoccurring cancers
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.
Interlaboratory proficiency testing for tumor marker tests, and for clinical tests more generally, is routine in Europe and an emerging field in the United States. New York state is prominent in advocating such research.

## List of commonly used markers

| Tumor marker | Associated tumor types |
| Alpha fetoprotein (AFP) | germ cell tumor, hepatocellular carcinoma |
| CA15-3 | breast cancer |
| CA27.29 | breast cancer |
| CA19-9 | Mainly pancreatic cancer, but also colorectal cancer and other types of gastrointestinal cancer. |
| CA-125 | Mainly ovarian cancer, but may also be elevated in for example endometrial cancer, fallopian tube cancer, lung cancer, breast cancer and gastrointestinal cancer. |
| Calcitonin | medullary thyroid carcinoma |
| Calretinin | 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 |
| CD34 | hemangiopericytoma/solitary fibrous tumor, pleomorphic lipoma, gastrointestinal stromal tumor, dermatofibrosarcoma protuberans |
| CD99 | Ewing sarcoma, primitive neuroectodermal tumor, hemangiopericytoma/solitary fibrous tumor, synovial sarcoma, lymphoma, leukemia, sex cord-gonadal stromal tumor |
| CD117 | gastrointestinal stromal tumor, mastocytosis, seminoma |
| Chromogranin | neuroendocrine tumor |
| Chromosomes 3, 7, 17, and 9p21 | bladder cancer |
| Cytokeratin | Many types of carcinoma, some types of sarcoma |
| Desmin | 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 |
| HMB-45 | melanoma, PEComa (for example angiomyolipoma), clear cell carcinoma, adrenocortical carcinoma |
| Human chorionic gonadotropin (hCG) | gestational trophoblastic disease, germ cell tumor, choriocarcinoma |
| immunoglobulin | lymphoma, leukemia |
| inhibin | 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) |
| Myo D1 | rhabdomyosarcoma, small-blue-round-cell tumor |
| muscle-specific actin (MSA) | myosarcoma (leiomyosarcoma, rhabdomyosarcoma) |
| neurofilament | 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 |
| S100 protein | 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 |
| synaptophysin | neuroendocrine tumor |
| thymidine kinase | lymphoma, leukemia, lung cancer, prostate cancer |
| 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 |
| Tumor M2-PK | colorectal cancer, Breast cancer, renal cell carcinoma lung cancer, pancreatic cancer, esophageal cancer, stomach cancer,cervical cancer, ovarian cancer, |
| vimentin | sarcoma, renal cell carcinoma, endometrial cancer, lung carcinoma, lymphoma, leukemia, melanoma |

## Accuracy and specific use

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.