Tumor Markers Lecture Notes PDF

Tumor markers Clinical Chemistry 5th stage College of Pharmacy-University of Baghdad Dr. Zahraa Mohammed  tumor markers substances that can be found in the body in the presence of cancer. mostly found in the blood or urine, also can be...

Tumor markers Clinical Chemistry 5th stage College of Pharmacy-University of Baghdad Dr. Zahraa Mohammed  tumor markers substances that can be found in the body in the presence of cancer. mostly found in the blood or urine, also can be found in tumors and other tissue. can be products of the cancer cells themselves, or made by the body in response to cancer or other conditions.  Ideal tumor marker 1.Specificity for a single type of cancer 2. High sensitivity for cancerous growth 3. Correlation of marker level with tumor size 4. Homogeneous ( minimal post-translational modifications) 5.Short half-life in circulation Occasionally,tumors may dedifferentiate and fail to express the marker.  Indications of measurement 1. screen for disease :Very few markers are sufficiently sensitive or specific to be used to screening of tumor. 2. diagnose a tumour : little can be used to confirm a diagnosis when determine in plasma or urine. 3. determine the prognosis :when the concentration of a specific marker is related to the mass or spread of the tumour.  Indications of measurment 4. To monitor the response to treatment: If a the rate of decrease in concentration can be used to assess the response to treatment (surgery, chemotherapy or radiotherapy). 5. To identify the recurrence of a tumor If the concentration of the marker was previously raised, intermittent measurement during remission may be used to identify recurrence.  classes 1.oncofetal protein (present during embryogenesis) :CEA ,AFP 2:mucin glycoproteins: CA-125, CA19-9,CA15-3, CA -27-29 3.enzymes:, NSE ,PSA 4.hormones:ACTH, hCG 5.receptors:ER , PR 6.DNA markers :BRCA-1 , BRCA-2 7. Metabolites (norepinephrine, epinephrine)  Prostate-specific antigen marker for prostatic carcinoma protein , homologous with the protease kallikrein family plasma 3 days. help liquidize semen. Its level is raised in benign prostatic hyperplasia (BPH) and prostatic carcinoma , prostate infection and after rectal examination. level should be adjusted according to age (↑ with age) and volume(for volume by ultrasound examination).  Prostate-specific antigen there is overlap in values of PSA in BPH and prostatic carcinoma (limitation in Dx). After a radical prostatectomy, plasma PSA levels become undetectable at 2–3 weeks. Finasteride, used to treat BPH, decreases plasma PSA by up to 50 %. The PSA is bound in the plasma to either α1- antichymotrypsin or α2-macroglobulin. The concentration of bound PSA is higher in prostate carcinoma, whereas that of free PSA is higher in BPH. The ratio of free to total PSA is lower prostatic carcinoma  Prostate-specific antigen The PSA index : the percentage of the total plasma PSA that is free; an index above about 17 % is suggestive of BPH and one of less than 17 % of prostate carcinoma. High Plasma PSA concentrations is suggestive of carcinoma, (carcinoma may be present even if values fall within the reference range). above 20 μg/L is suggestive of prostatic carcinoma that has spread beyond the prostate gland.  Prostate-specific antigen Plasma PSA assays in conjunction with digital rectal examination used as part of a screening programme for prostatic carcinoma in at-risk males. no universally agreed screening protocol for prostatic carcinoma in the general population. Prostate biopsy indicated if the PSA concentration is above 10 μg/L  Carcinoembryonic antigen may be produced by some malignant tumours, especially colorectal carcinomas. If the initial plasma concentration is raised, serial plasma CEA estimations may help to monitor the effectiveness of, or recurrence after, treatment. Plasma concentrations correlate poorly with tumour mass, very high concentration usually indicates a bad prognosis. Plasma concentrations may also rise in non-malignant disease of the gastrointestinal tract and in smokers. the test is non-specific  α-Fetoprotein its synthesis suppressed as the fetus matures. Concentrations may be very high in the plasma of patients with hepatocellular carcinoma (primary hepatomas and hepatoblastomas) and teratoma. Moderately raised concentrations may be due to non-malignant liver disease.  Human chorionic gonadotrophin (hCG) is normally produced by the placenta, but also by trophoblastic cells of gonadal and extragonadal germ cell tumours. Ectopic secretion observed in some bronchial carcinomas. The measurement can be used to screen for choriocarcinoma in women who have had a hydatidiform mole. Plasma concentrations may be raised in patients with malignancy of the gonads such as seminomas, may be used to monitor the response to treatment and tumour recurrence.  CA-125 the concentration may be raised in the plasma of patients with ovarian carcinoma (OC )(80% of epithelial OC ). Have limited value in screening and diagnosis ,benefit in follow up It can be raised in pregnancy, fibroids, liver and pancreatic disease, endometriosis and pelvic inflammatory disease. it can be raised in other malignant diseases such as lung, breast , colon carcinoma.  CA-125 ultrasound scan of the abdomen and pelvis aid in screening for ovarian carcinoma in high level. Human epididymis protein (HE4) : a tumor marker for ovarian carcinoma (also overexpressed in endometrial cancer). Both are determined before treatment and after treatment (serial estimation)  Breast cancer concentration of CA-15-3 may be raised in the plasma of some patients with advanced breast carcinoma also may be raised in liver cirrhosis, and with ovarian cysts.  Breast cancer family history of breast cancer (BC) is indicator for increased risk of BC BRCA 1 and BRCA 2 the most important genes 5% of BC and OC attributed to mutation with BRCA1(also associated with increased risk of colon and prostate cancer) 3% of BC and OC attributed to families with mutation with BRCA2 gene  Breast cancer Estrogen receptor (ER) and progesteron receptor (PR) assays to assess prognosis Evaluate relative conc of these receptors in BC tissue excised during surgery Aid in selection of appropriate treatment Her2 overexpressed in 25-30% of BC All Aid in selection of appropriate treatment Patient with positive ER , PR mostly respond to endocrine therapy  CA-19-9 The concentration may be raised in the plasma of patients with pancreatic or colorectal carcinoma and obstructive liver disease Can increase in ,hepatic ,thyroid ,pulmonary disease ,DM  Thyroid cancers Thyroglobulin: high-molecular-weight protein , produced in the follicular cells of the thyroid. Its concentration is raised in follicular or papillary carcinoma of the thyroid. Antibody should measured (presence ↓ the level) Calcitonin:secreted by parafollicular C-cells of thyroid gland Elevated in medullary thyroid carcinoma (MTC) Levels may elevated before any clinical evidence of tumor presence MTC can occur as inherited ,calcitonin stimulation test can serve as screening tool  Other tumor markers Serum paraprotein and urinary Bence Jones protein for multiple myeloma). Plasma lactate dehydrogenase (LDH): the activity can be raised in certain haematological tumours such as lymphomas. Placental alkaline phosphatase: true placental alkaline phosphatase and placental-like isoenzyme levels are raised in seminoma and dysgerminoma. In conjunction with AFP and hCG, it is useful in the diagnosis and monitoring of extragonadal and gonadal germ cell tumors. plasma levels are also elevated in smokers  Other tumor markers Neuronal-specific enolase (NSE) : derived from neurodectal tissue. plasma levels may be raised in small cell lung carcinoma and neuroblastoma. Inhibin: this is secreted by the granulosa cells of the ovary and by the Sertoli cells of the testis. It can be used as a plasma tumor marker of ovarian granulosa cell tumors and testicular Sertoli cell tumors.  Other tumor markers Squamous cell carcinoma antigen: this is a plasma tumor marker of potential use in squamous cell carcinoma of the cervix. Chromogranin A : released from neuroendocrine cells such as in phaeochromocytoma and carcinoid tumours. Protein S100B is a calcium-binding protein. It is expressed in brain astrocytes and glial cells and also in melanocytes and may be useful in monitoring therapy in malignant melanoma.  Roles for tumor markers Determine risk (PSA) Screen for early cancer (calcitonin, occult blood) Diagnose a type of cancer (hCG, catecholamines) Estimate prognosis (CA125) Predict response to therapy (CA15-3, CA125, PSA, hCG) Monitor for disease recurrence or progression (most widely used function) Therapeutic selection (her2/neu, ER , PR )