Tumer markers Clinical Tests - PowerPoint Presentation

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Tumer

markers

Clinical Tests Lec. 6

3rd Grade – Fall Semester 2021-2022

Goran N. Saleh

goran.nori@tiu.edu.iq

21/12/2021

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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.

Tumor Markers

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Clinical Application of Tumor Markers

Screening - limitedDiagnosis - limitedPrognosis -

limitedTumor staging - limitedTumor localization / radiotherapy - limitedMonitoring the effectiveness of therapy -

importantDetecting tumor recurrence or remission - important

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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.

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Telomerase is composed of both RNA and protein

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How Telomerase extends the Telomere

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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)

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Telomerase and CancerThe presence of telomerase in cancer cells allows them to maintain telomere length while they proliferate

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Genetic Markers

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Types of oncogenes

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Type I oncogene:

Spleen focus-forming virus (SFFV) is a retrovirus that induces erythroleukemia in miceSFFV encodes a protein, gp55, that activates Epo receptors on erythroid precursor cells

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Type II: HER-2/neu 0ncogene

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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.

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BCR/ABL oncogene

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Tumor suppressor genes1- p53

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2- Retinoblastoma gene

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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

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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.

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Alpha fetoprotein

Glycoprotein, found in fetal liver, yolk sac, GI tract, biochemically related to albumin in adultshalf-life: 4~6 daysNormal serum levels; At birth 30 ng/ml

>1 years old (adult) <10 ng/mlIncreased in 70% HCC, elevated in hepatoblastoma, 20~70% germ cell tumors (yolk sac tumors, embryonal cell carcinoma) of testis and ovary, except dysgerminoma

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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

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Enzymes as tumor markersAlkaline phosphatase.

Lactate dehyrogenase (LDH).Neurone specific enolase.Prostatic acid phospatase.Prostate specific antigen (PSA).Urokinase plasminogen activator system.Cathepsins.Matrix metalloproteinase.

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Hormones as tumor makers

Hormone

Type of cancer

ACTH

Small cell lung cancer – Cushing's syndrome – Cancer colon- cancer prostate- cancer ovary

Calcitonin

Medullary carcinoma of the thyroid

HCG

Chorio carcinoma – Testicular tumors

Human Placental Lactogen

Trophoplastic tumors – gonads, lung and breast cancers

ADH

Small cell lung cancer – tumors of adrenal cortex, pancreas and duodenum.

Glucagon

Glucagonoma

Catecholamines and its metabolites

Pheochromocytoma

Seritonin and 5HIAA

Carcinoid tumors

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Cytokeratins

Tissue polypeptide antigen (TPA)

Proliferation marker useful for monitoring metastasis in breast , colon and ovarian cancers

Differentiating

choriocacinoma and HCC.

Tissue polypeptide specific antigen (TPS)

Antigenic site on TPA complex.

Associated with proliferative activity of lung tumors

Cytokeratin 19 fragments (CYFRA)

Used for staging, monitoring treatment and follow up of lung cancer

Squamous Cell Carcinoma Antigen (SCCA)

Elevated in a variety of squamous cell carcinoma of cervix, lung, head and neck, digestive tract, ovaries and urogenital tract

Used as a prognostic marker and detection of recurrence.

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Carbohydrate Markers (CA)

CA 15-3

monitor treatment and to detect recurrence in cancer breast

Normal: <31 U/ml

↑in 20% with localized breast cancer, ~80% with metastatic disease, esp. if with bone

involvmentSpecificity of 86%, sensitivity of 30%

Also increased in gastric, pancreatic, cervical and lung cancer

CA 27.29

CA 549

High molecular glycoprotein - Increased in cancer breast

CA 125

Cell surface glycoprotein, present during embryonic development of

coelomic

epithelium and is present in adult structures derived from it

Normal : <35 U/ml, t ½ : 4~5 days

For follow up of ovarian cancer, an increase may predict recurrent disease, may precede clinical recurrence by months. Correlate with tumor bulk

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Blood group antigen- related cancer markers

CA 19-9

Elevated in patients with mucin-secreting cancers (colorectal, pancreatic, ovarian and gastric cancers)

Diagnosis, monitor, detect relapse in ovarian cancer, 70% specificity and 90% sensitivity

Mild ↑in

pancreatitis

CA 242

A marker of pancreatic and colorectal cancers

CA 72-4

A marker for carcinoma of GIT and ovary.

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Proteins as tumor markers

Β

2 microglobulin

Multiple myeloma – B -cell lymphoma

- CLL- Waldenstrom macroglobulinaemia

Correlates with tumor burden, prognosis, response to therapy. Increase with poor renal function

C-peptide

Insulinoma

Ferritin

Cancer liver, lung, breast and leukaemias

immunoglobulins

Multiple myeloma and B-cell lymphoma

Tyrosinase

Use RT-PCR to detect hematogenous spread of melanoma cells from a solid tumor in peripheral blood

S100B protein

↑in 70% with stage IV metastasized melanoma

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Proteins as tumor markers

Melanoma associated antigen

Melanoma

Pancreas- associated antigen

Pancreas and stomach cancers

Pregnancy specific protein-1

Trophoblastic and germ cell tumors

Prothrombin precursor

Hepatocellular cacinoma

Thyroglobulin

Tissue-specific

, glycoprotein produced by thyroid follicular cells

normal: <60 ug/L

Increased in cancer thyroid. Also increased in breast and lung cancers

Tumor-associated trypsin inhibitor

Lung, Gastro intestinal and

ovarial

tumors

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Receptors as tumor markers

Estrogen Receptors (ER)

2 isoforms: ER

α + ER

β

ERα → better prognosis, predictor of relapse in cancer breast. Useful when deciding an adjuvant hormone treatment

ER

β

→ distinct biological roles and ligand binding specificity, good prognostic factor, correlate with low grade and negative axillary LN status

Progesterone Receptors

(PR)

Useful prognostic maker in cancer breast with ER assay because PR synthesis is dependent on estrogen action

Epidermal growth factor receptors (EGFR)

Overexpression of EGFR has prognostic value in many cancers: head and neck, ovarian, cervical bladder and

esophgeal

cancers

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