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Tumor Markers. Dr/ Ehsan Mohamed Rizk. A substance that is present in or produced by a tumor or by the host in response to tumor ’s presence.
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Tumor Markers Dr/ Ehsan Mohamed Rizk
A substance that is present in or produced by a tumor or by the host in response to tumor’s presence. An ideal tumor marker: specific, sensitive, has short half life, its concentration is correlated with tumor burden and its assay is easy, reliable and cost effective.
Clinical Application of Tumor Markers • Screening - limited • Diagnosis - limited • Prognosis - limited • Tumor staging - limited • Tumor localization / radiotherapy - limited • Monitoring the effectiveness of therapy - important • Detecting tumor recurrence or remission - important
Without some form of correction the end replication leads to the loss of 50-100 nucleotides from the newly synthesized lagging strand at each chromosome end in each round of duplication In mammalian (and many other) cells, the solution to this problem is that chromosome ends have a special duplication machinery = Telomerase Telomerase (special type of reverse transcriptase) is a protein-RNA complex that carry an RNA template for synthesizing a repeated G-rich telomere. Telomerase is unique in carrying its own RNA template with it all the time.
Telomerase and Senescence In most somatic tissues, telomerase is expressed at very low levels or not at all -- as cells divide, telomeres shorten Short telomeres may be a signal for cells to senesce (stop dividing)
Telomerase and Cancer The presence of telomerase in cancer cells allows them to maintain telomere length while they proliferate
Type I oncogene: • Spleen focus-forming virus (SFFV) is a retrovirus that induces erythroleukemia in mice • SFFV encodes a protein, gp55, that activates Epo receptors on erythroid precursor cells
RAS oncogene Mutated N-ras gene is found in neuroblastoma and AML. Mutated K-ras gene is found in pancreatic, colon, lung and bladder cancers.
BRCA1 and BRCA2 • BRCA 1 gene is located on ch 19 while BRCA 2 gerne is located on ch 13. • Screening for familial breast-ovarian cancer syndrome, and breast cancer in early-onset breast cancer families
Oncofetal Antigens • Carcinoembryonic antigen: • Described by Gold and Freedman in 1965 as a marker of Colorectal Cancer. • It also increases in pancreatic, gastric, lung, ovarian, uterine and breast cancers. • Molecular mass of approximately 200 kDa. • Glycoprotein with carbohydrate composition ranging from 45 – 55 % encoded by a gene located on chromosome 19. • CEA levels 5 – 10 times upper limit of normal suggests cancer colon. • CEA useful for staging and monitoring treatment but not for screening.
Alpha fetoprotein • Glycoprotein, found in fetal liver, yolk sac, GI tract, biochemically related to albumin in adults • half-life: 4~6 days • Normal serum levels; At birth 30 ng/ml >1 years old (adult) <10 ng/ml • Increased in 70% HCC, elevated in hepatoblastoma, 20~70% germ cell tumors (yolk sac tumors, embryonal cell carcinoma) of testis and ovary, except dysgerminoma
The absolute AFP level correlates with tumor bulk • CSF to plasma ratio of AFP > 1:40 → suggest CNS involvement. • AFP-L3 %: > 10 % suggests presence of HCC. • Increase in benign conditions that cause hepatic parenchymal inflammation, hepatic necrosis and hepatic regeneration, ex. hepatitis, pregnancy, primary biliary cirrhosis, extrahepatic biliary obstruction
Enzymes as tumor markers • Alkaline phosphatase. • Lactate dehyrogenase (LDH). • Neurone specific enolase. • Prostatic acid phospatase. • Prostate specific antigen (PSA). • Urokinase plasminogen activator system. • Cathepsins. • Matrix metalloproteinase.
