Tumor Markers
· Human epididymis protein 4 (HE4), a new marker for ovarian carcinoma, is the product of the WFDC2 (HE4) gene that is overexpressed in patients with ovarian carcinoma. Several publications have demonstrated HE4's su-periority over CA-125 as an OC biomarker. The combination of CA-125 with HE4 achieved the highest sensitivity compared with all other single markers or dual-marker combinations. HE4 has sensitivity similar to CA-125 in detecting late-stage disease and greater specificity than CA-125 in detecting early ovarian cancer. HE4 is differently expressed during the phases of the menstrual cycle in healthy young women. The menstrual cycle phase-dependent variability appears indicated in the interpretation of the results.
HE4 levels were elevated in both endometrial and ovarian malignancies, but not in endometriotic lesions. These results thus provide additional evidence for HE4's complementary association with CA-125 in the detection of OC. Elevated HE4 levels are associated with ovarian cancer but are not disease-specific and do not preclude the presence of cancer, nor are elevated results an absolute indication of malignancy. A change in HE4 level of ≥25% is considered significant. An increase of this magnitude suggests recurrence or disease progression, while a decrease
of this magnitude suggests therapeutic response.
False positive results can be detected with ovarial cysts, adnexitis or benign tumors. Levels of HE4 within the reference range HE4 should not be used for monitoring patients with mucinous or germ cell ovarian cancer. Results should be interpreted in conjunction with other clinical and laboratory findings
· JAK2 V617F mutation analysis
The JAK2 V617F mutation is a sensitive marker for polycythaemia vera (PV), essential thrombocythemia (ET) as well as idiopathic myelofibrosis (iMF) and therefore a diagnostic criterion for myeloproliferative diseases. The JAK2 mutation is a somatic and thus an acquired point mutation; it affects the Janus kinase 2, a cytoplasmic tyrosine kinase which is involved in the receptor-mediated transmission of intracellular signals of various growth factors and cytokines. The V617F mutation in exon 14 of the JAK2 gene leads to an exchange of the amino acid valine (V) by phenylalanine (F); an increase in kinase activity is the result. This constitutive activation finally leads to an increased division rate of the affected cells.
· Squamous cell carcinoma antigen
SCC, expressed as SCC-A (antigen) from transformed squamous epithelium cells, is a valid tumormarker the monitoring of squamous cell carcinoma of the cervix (sensitivity >80%) and lung (sensitivity >70%), esophagus, anus and nose-throat neoplasia (besides CEA with a lower sensitivity). The SCC is not recommended as a screening for primary diagnosis. A negative result does not exclude a malignoma. Elevated levels can also be detected with benign diseases f.e. hepatobilial disturbances, kidney insufficiency or other gynecological disorders.
· 5-Hydroxyindolacetic acid in urine (HIAA)
5-HIAA is the main metabolite of serotonin, which is formed out of tryptophan. Serotonin is either stored in neurosecretoric vesicles or released into the blood circulation system. Most of the serotonin in plasma, is used by thrombocytes and biotransformed into 5-HIAA (elevated in carcinoid syndrome). Serotonin has a positive effect on GIT activity especially duodenum and jejunum. Severe diarrheas are observed in carcinoid syndrome. Further symptoms of the carcinoid syndrome are: flush, facial telangiectasis, abdominal convulsions, asthma-similar attacks and endocardial fibrosis of the right heart.
· Melanoma-inhibiting activity (MIA)
Melanoma-inhibiting activity (MIA) is a 107 amino-acid protein secreted from melanoma cells and frequently detectable at high concentration in the serum of patients with advanced melanoma. Early studies suggested that MIA may be a useful serum tumor-marker for detection of recurrent or progressive disease. However, MIA has not been recognized as sensitive marker for relapse in patients clinically free of disease after treatment.
· Chromogranin A (CGA)
This is a 68 kDa calcium-binding glycoprotein which is produced in neuroendocrine cells (in normal as well as in tumor cells). An essential role for CGA was described in the differentiation of neuroendocrine tissues. Increased CGA concentrations in blood point to neuroendocrine tumors or metastases independent from their localization. High CGA levels in blood seem to reflect advanced disease stages. In different studies, a specificity and a sensitivity for CGA of 75-100% - depending on the disease - were described. Chromogranin A is considered as a more sensitive, but relatively nonspecific marker of neuroendocrine tissue. The chromogranin A concentration is usually detected in parallel with the excretion of the 5-hydroxy-indole acetic acid (degradation product of serotonin) in urine.
