Testicular cancer is one of the few cancers associated with tumor markers. It is not clear why testicular cancers release these markers. Most testis cancers that secrete tumor markers are nonseminomatous germ cell tumors (NSGCT), and 85 percent of NSGCT will secrete at least one tumor marker. These cancers often develop from the germ cells in the testis that have the potential to transform into a variety of cell types. It is hypothesized that as these germ cells turn into cancer cells, they turn on genes and secrete proteins usually only released during fetal development.  

Despite the lack of understanding as to the cause of elevated tumor markers, these markers are well established to help in the diagnosis, prognosis, treatment and monitoring of testis cancer. However, many patients and their families are confused about where tumor markers come from, what an elevation in a level means and how markers should change over time. There are three important tumor markers for testicular cancer: 

• Alpha-fetoprotein (AFP) 
• Human chorionic gonadotropin (HCG) 
• Lactate dehydrogenase (LDH) 

MicroRNAs (miRNA) are emerging as promising biomarkers for testicular cancer diagnosis and therapeutic monitoring. Research efforts are ongoing to further study these candidate biomarkers and understand their potential clinical use. 

Alpha-fetoprotein 

Normal range: <10 micrograms/L 

Half life: 5 to 7 days 

AFP is a protein secreted by the fetal yolk sac, liver and gastrointestinal tract and appears in high levels in the blood of the fetus. AFP can be secreted by NSGCT that contain embryonal carcinoma, yolk sac tumor or teratoma. By definition, seminoma does not secrete AFP. Therefore any patient with an elevated AFP must have a nonseminomatous component of testis cancer. 

AFP can be elevated in patients with a number of other malignancies, including with hepatocellular (liver) carcinoma, cancer of the stomach, pancreas, biliary tract and lung. In addition, AFP elevation is associated with a number of nonmalignant diseases, including diseases of the liver and the rare diseases ataxic telangiectasia and hereditary tyrosinemia. 

Human Chorionic Gonadotropin (HCG) 

Normal range: <5 IU/L 

Half life: 24 to 36 hours 

HCG is a glycoprotein produced by the placenta to maintain the corpus luteum during pregnancy. HCG can be elevated in a number of other malignancies, including cancers of the liver, lung, pancreas and stomach. In germ cell tumors of the testis, including both seminomas and NSGCT, cancerous cells can transform into syncytiotrophoblasts (a normal component of the placenta) and secrete HCG. Levels greater than 5,000 IU are usually indicative of NSGCT, and in NSGCT, higher levels of HCG are associated with a worse prognosis. However, HCG-producing seminoma (approximately 15 percent of seminomas) has the same prognosis as seminoma that does not produce HCG.   
The HCG molecule is cross-reactive with another protein, luteinizing hormone (LH). Hypogonadal men can have elevated LH levels and subsequently falsely elevated HCG levels — administration of exogenous testosterone can help distinguish HCG elevation from hypogonadism from HCG from testis cancer. In addition, marijuana smoking has been associated with an elevated HCG level. 

Testicular Lactate Dehydrogenase (LDH) 

Normal range: <250 U/L (varies slightly by assay) 

Half life: 24 hours 

LDH is a cellular enzyme found in every tissue in the body. Highest concentrations of LDH in normal tissue are found in muscle (including skeletal, cardiac and smooth muscle), liver and brain. LDH is expressed on chromosome 12p, which is often amplified in testis cancer cells. LDH is less specific for testis cancer than HCG or AFP. However, elevated LDH levels are correlated to high tumor burden in seminoma and recurrence in NSGCT.