Tumor Markers

Definition

 Tumor markers can be defines as metabolic products produced by tumor cells

or by a host in response to a tumor or related to the presence of tumor used
to differentiate it from normal tissue or to determine the presence of a
tumor, found in the body fluids or tumor surfaces of patients with cancer.
 Tumor markers are substances which can be detected in higher than normal
amounts in the blood, urine, or body tissues of some patients with certain
types of cancer.
The ideal tumor marker

 Highly specific
 Highly sensitive
 Able to differentiate between neoplastic and non-neoplastic disease
 Its levels should be preceding the neoplastic process
 It should be easily assayable
 Should either be a universal marker for all types of malignancies or specific to
one type of malignancy
 It should be able to indicate all changes in cancer patients receiving
treatment
 He first tumor marker reported was Bence Jones Protein in multiple myeloma in 1847.
 Since then numerous potential tumor markers have been reported . Tissue polypeptide
antigen(TPA) is a substance reported by Bjorklund in 1957.
 The second era of tumor markers discovery was from 1928- 1963 includes identification of
various enzymes, hormones, isoenzymes and proteins. The third era of Tumor markers included
the discovery of alpha feto protein and carcinoembryonic antigen.
 The fourth era of tumor markers history from 1975 had discovery of ca-125, ca 15-3 and ca 27.29
Clinical Applications

 Screening for cancer

 Diagnosing cancer
 Evaluation cancer prognosis
 Prediction of therapeutic response
 Tumor staging
 Detecting tumor recurrence
 Localizing tumor and directing radio therapeutic agents
 Monitoring effectiveness of cancer therapy
Classification of tumor markers

 Enzymes – PAP, Prostate Specific Antigen(PSA), Placental alkaline

phosphatase(PALP)
 Hormones
 Oncofetal antigens – AFP, CEA
 Cytokeratins
 Carbohydrate markers
 Blood group antigens
 Proteins – Ferritin, Glycoprotein, Immunoglobulins
 Receptors – Estrogen receptor, Progesterone receptor
 Genetic markers
Alkaline phosphatase

 Found in liver, bone, placenta

 Primary or secondary liver cancer
 Metastatic cancer with bone or liver
 PALP – trophoblastic sera of pregnant women
 PALP – ovarian, lung, trophoblastic GI cancers, Hodgkins disease
Creatine kinase

 Dimer – M and B forms

 CK1-BB-brain, prostate, git, lung,bladder, uterus
 CK2-MB-cardiac muscle
 CK3-b-skeletal and cardiac muscle
 Ck1- prostate cancer, Small cell lung cancer
Lactate dehydrogenase

 Non specific
 LDH- liver, seminoma, neuroblastoma, non hodgkins lymphoma, acute
leukemia
Neuron specific enolase

 Neuronal tissue, neuroendocrine tissue

 NSE – SCLC, neuroblastoma, pheochromocytoma, medullary carcinoma of
thyroid
 High levels – poor prognostic factor
Hormones

 ACTH – cushings syndrome, SCLC

 ADH – SCLC, adrenal cortex, pancreatic
 Bombesin – SCLC
 Calcitonin – medullary thyroid
 Gastrin – Glucagonoma
 GH – pituitary adenoma, renal, lung
 HCG – Embryonal, choriocarcinoma, testicular
 HPL- Trophoblastic, Gonad, lung
Cytokeratins

 Are proteins of cytoskeletal intermediate filaments

 Type 1 – smaller and acidic
 Type 2 – larger and neutral to basic
 Immuno radiometric assay
 Tissue polypeptide specific antigen – Lung
 Cytokeratin 19 fracments – non small cell lung cancer
Carbohydrate markers

 Antigens on the tumor cell surface or secreted by tumor cells

 More specific
 High molecular weight mucins or blood group antigens
 CA 19-9 – pancreatic, GI, hepatic
 CA 19-5 – GI,pancreatic, ovarian
 CA 50 – pancreatic, GI
 CA – 125 – ovarian, endometrial
 Can be identified by radiometric assay
Proteins

 Tumor markers that are not enzymes, hormones or high in carbohydrate

content
 Thyroglobulin – differentiated thyroid cancer
 B2 macroglobulin- multiple myeloma, B-cell lymphoma
 C-peptide – Insulinoma
 Ferritin – liver, lung , breast, leukemia
 Immunoglobulin – multiple myeloma, Lymphoma
 Pancreas associated antigen – pancreas, stomach
Receptors

 Estrogen and progesterone receptors- in breast cancer, indicators of hormonal

therapy prognosis
Genetic markers

 Oncogenes – Activations of proto oncogenes – ancer

 Suppresor genes – Loss of gene – deletion or monosomy – cancer

 Oncogenes
1. Ras genes – leukemia, lymphoma
2. C-myc gene – leukemia, lymphoma, sclc
3. Bcl 2 – lymphoma, myeloma, leukemia
4. Bcr – ABL gene - CML
 Tumor suppressor genes
1. Retinoblastoma gene – Retinoblastoma
2. P53 gene – colorectal, breast, lung
3. APC – colon
4. NF1( neurofibromatosis type 1) – Von Recklinghausen disease
5. BRCA 1 and 2 – breast, ovarian
Prostate specific antigen

 Gammaseminoprotein due to its presence in seminal plasma

 It is a monomer
 Epithelial cells of acini and ducts of prostate
 PSA a neutral serine protease
 For screening, staging and monitoring treatment and recurrence of prostate
cancer
Prostatic acid phosphatase

 200 times more abundant in prostate tissue than in any other tissue
 Not sensitive as PSA for screening or detection of early cancer
 Is useful only in stagin apparently localized disease, i.e, primary prostate
cancer before definitive therapy such as radical prostatectomy
Alpha Fetoprotein

 Expressed either during malignancy or during intra uterine or early postnatal

life
 <10 micro gram per ml
 The significance of AFP is
1. Prenatal diagnosis of open spina bifida
2. Anencephaly
3. Atresia of esophagus
4. Multiple pregnancy
 Role of AFP in malignancy
 Diagnosis, prognosis and monitoring of
1. Primary hepatocellular carcinoma
2. Hepatoblastoma, Non seminomatous testicular germ cell tumors
3. Germ cell tumors of ovary and extragonadal germ cell tumors
4. Malignancies of gastrointestinal tract, pancreas, lungs , kidney and breast
Human chorionic Gonadotropin

 A marker of germ cell tumors and trophoblastic disease

 Peak – 10th and 12th weeks of gestation
 Men and non pregnant women have <5 IU/ml and post menopausal women
<10IU/ml
 HCG is a marker of first choice for gonadal choriocarcinoma and extragonadal
choriocarcinoma
Carcino Embryongenic antigen

 Colorectal, GI, lung, and breast carcinoma

 Primary use in detection of local and metastatic cancer recurrence
 A persistently elevated CEA – colon cancer
 CEA declines – after successful initial therapy
 CEA stable – remission
 Rising level in dicate recurrence of disease
 Preoperative CEA level has prognostic significance
Tissue polypeptide antigen

 Moderate elevation in many diseases and in pregnancy

 The marked elevation in breast, lung, gastrointestinal, urological.
Gynecological cancer
 Sensitive but non specific tumor marker
Analysis

 Enzyme assay
 Immunoassay
 Receptor assay
 Mass spectrometry interfaced with liquid or gas chromatographs
 Microarrays