Tumor Markers for Students

7/30/2019 Tumor Markers for Students

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TUMOR MARKERS

Geromil J. Lara, RMT, MSMT



GROWTH REGULATION

• 2 Major Processes

• CANCER

• Refers to the uncontrolled growth of cells that can develop into a solid mass or tumor





NEOPLASIA VS HYPERPLASIA

Hyperplasia

• Involves the multiplication

of cells in an organ of tissue

• Consequently have

increased in volume

• Increase in tumor markersis transient

Neoplasia

• Involves the possibility of

normal cells undergoing

cancerous proliferation ashyperplasia taking place

under less controlled

conditions

• Increase in tumor markersis a long lasting

phenomenon



TYPES OF TUMOR MARKERS

• Any molecule that can be identified with

malignant transformation, proliferation, de-

differentiation, and metastases of tumor cells

can be used as tumor marker

• The clinical value depends on its intended

clinical use, as well as its specificity and

sensitivity



SENSITIVITY VS SPECIFICITY

Sensitivity

• Assay will detect all

patients with a particular

type of cancer

Specificity

• Assay will identify only the

patients with the specific

type of tumor and notthose with benign or

nonmalignant diseases



CHARACTERISTICS OF AN IDEAL TUMOR

MARKER

• Specificity for cancer

• Sensitivity for cancer

• The amount of marker produced correlateswell with the tumor load

• There should be a consistent concentration of

the tumor marker in patients with stabledisease



CHARACTERISTICS OF AN IDEAL TUMOR

MARKER

• Half-life of the marker needs to be short

enough

• Levels of the marker (initial and serial) should

have prognostic value

• The assay for the marker should be

analytically sensitive, specific, accurate,

precise, easy to perform, inexpensive, and

rapid



USES OF TUMOR MARKERS

• Screening of disease in asymptomatic

population

• Diagnosis of disease in symptomatic patients

• Aid in clinical staging



USES OF TUMOR MARKERS



CLASSIFICATION OF

TUMOR MARKERS

• Chemical Structure

• Function

• Method of Detection

• Anatomic Source



CATEGORIES OF

TUMOR MARKERS

• Enzymes and Isoenzymes

• Hormones, Neurotransmitters, and their

Metabolites

• Receptors

• Proteins

• Genetic Markers• Other Markers like sialic acid conjugates,

polyamines, and amino acids



I. ENZYMES AS

TUMOR MARKERS

• ALKALINE PHOSPHATASE

• Metastatic CA of bone, hepatocellular carcinoma,

osteosarcoma, lymphoma, leukemia

• Determination of liver and

bone involvement

• Nonspecific elevation in many bone-related and

liver cancers



I. ENZYMES AS

TUMOR MARKERS

• ACID PHOSPHATASE

• Prostatic adenocarcinoma

• Diagnose and monitor prostate cancer butmay not necessarily be found when

malignancy is present

• Useful for monitoring the success of surgical

prostatectomy and for detecting recurrence



I. ENZYMES AS

TUMOR MARKERS

• ALKALINE PHOSPHATASE

• Metastatic CA of bone, hepatocellular carcinoma,

osteosarcoma, lymphoma, leukemia

• Determination of liver and

bone involvement

• Nonspecific elevation in many bone-related and

liver cancers



I. ENZYMES AS

TUMOR MARKERS

• LACTATE DEHYDROGENASE

• _______: germ cell tumors

• _______: leukemias and lymphomas

• _______: colon, breast, lung, liver, stomachcancers



I. ENZYMES AS

TUMOR MARKERS

• NEURON-SPECIFIC ENOLASE

• Neuroblastoma, neurogenic tumors, small cell

carcinoma of the lung, glucagonomas,

insulinomas, carcinoid tumors, and

phaeochromocytoma



I. ENZYMES AS

TUMOR MARKERS

• CREATINE KINASE

• CK-BB Isoenzyme

• Malignant diseases - those of epithelial cell

origin

• Measured in CSF – brain tumors (nonspecific)



I. ENZYMES AS

TUMOR MARKERS

• AMS, LPS, TRYPSIN, AND RIBONUCLEASE

• Associated with pancreas

• RNAse may also be elevated in breast, colon,stomach, liver, and lung cancers



I. ENZYMES AS

TUMOR MARKERS

• 5’N and GGT

• Neither is specific for cancer



I. ENZYMES AS

TUMOR MARKERS

• Terminal Deoxynucleotidyl Transferase (TdT)

• Found in immature lymphoid cells



I. ENZYMES AS

TUMOR MARKERS

• Collagenase and Cathepsin D

• Proteases

• Synthesized and secreted by malignant cells

• Responsible for degrading the extracellular

matrix and thus permitting their invasion andmetastasis



I. ENZYMES AS

TUMOR MARKERS

• Histaminase

• Diamine Oxidase

• Medullary thyroid cancer to confirm high level

of calcitonin



I. ENZYMES AS

TUMOR MARKERS

• Muramidase

• Lysozyme



II. HORMONES AS

TUMOR MARKERS

• Human Chorionic Gonadotropin

• Dimeric hormone normally secreted by

trophoblasts in the placenta to maintain the

corpus luteum during pregnancy

• Trophoblastic CA, chorioCA, germ cell tumors

of the ovary and testis

• Occasionally elevated in ovarian CA and some

lung CA



II. HORMONES AS

TUMOR MARKERS

• Calcitonin

• Thyrocalcitonin

• Action is antagonistic to parathormone



II. HORMONES AS

TUMOR MARKERS

• ACTH

• Pituitary and ectopic ACTH-secreting tumors

• Small cell CA of the lung



II. HORMONES AS

TUMOR MARKERS

• CATHECOLAMINES AND THEIR METABOLITES

• Epinephrine and Norepinephrine

• Metanephrine, normetanephrine, 3-methoxytyramine, vanillylmandelic acid

(VMA), and homovanillic acid (HVA)



II. HORMONES AS

TUMOR MARKERS

• SEROTONIN AND 5-HYDROXYINDOLE-3-

ACETIC ACID

• Serotonin (5-Hydroxytryptamine) –

enterochromaffin cells of the GIT and brain

• Vasoconstrictor and carried largely by

platelets



II. HORMONES AS

TUMOR MARKERS

• SEROTONIN AND 5-HYDROXYINDOLE-3-

ACETIC ACID

• Serotonin (5-Hydroxytryptamine) –

enterochromaffin cells of the GIT and brain

• Vasoconstrictor and carried largely by

platelets

• Metabolized to 5-HIAA



II. HORMONES AS

TUMOR MARKERS

• ADH

• SIADH; pancreatic, duodenal, and adrenal

malignancies

• Small cell carcinoma of the lung



II. HORMONES AS

TUMOR MARKERS

• GASTRIN

• Secreted by G cells of the stomach and

duodenum

• D cells of the pancreas

• Stimulates secretion of gastric acid by the

parietal cells and pepsinogen and intrinsic

factor by the mucosal cells of the stomach



II. HORMONES AS

TUMOR MARKERS

• GASTRIN

•Gastrin-secreting duodenal and pancreatic

tumors (gastrinomas) are responsible for a

condition called Zollinger-Ellison Syndrome



II. HORMONES AS

TUMOR MARKERS

• GLUCAGON



II. HORMONES AS

TUMOR MARKERS

• INSULIN



II. HORMONES AS

TUMOR MARKERS

• PROLACTIN

• Secreted by the lactotropic cells of the

anterior pituitary, for lactation by the

mammary glands

• Pituitary adenomas can cause

hyperprolactinemia, which in turn can cause

galactorrhea



II. HORMONES AS

TUMOR MARKERS

• ESTROGEN AND ANDROGENS

• Estrogen-secreting tumors of ovarian in origin

• Estrogen-secreting tumors of the testis, the

adrenal cortex, and chorioepithelium



II. HORMONES AS

TUMOR MARKERS

• TSH

• Trophoblastic tumors

• Some tumors of the prostate, lung, blood, and

pituitary



II. HORMONES AS

TUMOR MARKERS

• Human Placental Lactogen

• Human Chorionic Somatomammotropin



II. HORMONES AS

TUMOR MARKERS

• Growth Hormone



II. HORMONES AS

TUMOR MARKERS

• Parathyroid Hormone



II. HORMONES AS

TUMOR MARKERS

• Erythropoietin



II. HORMONES AS

TUMOR MARKERS

• RENIN AND ALDOSTERONE



III. CARCINOEMBRYONIC PROTEINS

• a cancer-specific glycoprotein antigen of colon

carcinoma, also present in many

adenocarcinomas of endodermal origin and in

normal gastrointestinal tissues of humanembryos



CEA

• Not specific for colon but is found in a variety

of malignant and nonmalignant conditions

such as breast, GI, ling, ovary, pancreas, and

prostate cancers



AFP

• Produced by the fetal hepatocytes and the

yolk sac

• Germ cell tumors and hepatoma

• Yolk sac tumors

• Together with HCG, used to classify germ cell

tumors and gestational trophoblastic disease



IV. NONSPECIFIC

TUMOR MARKERS

• Tumor markers that are detectable

nonspecifically in many cancers

• Their concentrations are nevertheless sensitive

to changes of the tumor activity

• Are inexpensive and simple to measure and

are useful for monitoring therapy and

detecting recurrence

•



IV. NONSPECIFIC

TUMOR MARKERS

• Lipid-Associated Sialic Acid in the plasma

(LASA-P)

• generally used in conjunction with othertumor markers



V. CELL-SPECIFIC

TUMOR MARKERS

• Usually derived from epithelial cells

• Squamous Cell Antigen (SCA) is the marker

for Squamous Cell Carcinoma

• Chromogranin A (CgA) and Nonspecific

Enolase (NSE) are markers of Neuroendocrine

Cell Carcinoma



ALPHA-FETOPROTEIN (AFP)

• Major fetal serum protein and one of the

major carcinoembryonic proteins

• Found in patients with

• Transiently elevated during pregnancy and inbenign liver diseases (hepatitis and liver

cirrhosis)



β2-MICROGLOBULIN (β2M)

• A low-molecular-weight protein

• The constant light chain of the HLA expressed

on the surface of most nucleated cells

• Surfaces of lymphocytes and monocytes

• Elevated in solid tumors, lymphoproliferative

diseases and inflammatory disorders



CANCER ANTIGEN 125 (CA 125)

• First defined by a Murine Monoclonal

Antibody OC 125 raised against a serous

ovarian carcinoma cell line

• Associated with a HMW mucin-like

glycoprotein expressed in coelomic epithelium

during embryonic development and human

ovarian carcinoma cells




• Is a glycoprotein antigen in which a

carbohydrate moeity is also part of the

antigenic determinant

• Found greater than 80% of nonmucinous

epithelial ovarian carcinomas




• Not specific for ovarian carcinoma

• However, the appearance has been found to

precede clinical diagnoses of recurrent

diseases from 1 to 4 months

• Useful in detecting ovarian tumors at an early

stage



CANCER ANTIGEN 19-9 (CA 19-9)

• Appears as a mucin in the sera of cancer

patients but as a ganglioside in tumor cells




• Not organ specific

• Elevated in adenocarcinomas – pancreatic,

lung, colorectal, and gastric carcinomas




• GlycoCHON mucin present on mammary

epithelium

• Metastatic Breast Cancer



CANCER ANTIGEN 27-29

• Metastatic Breast Cancer



CANCER ANTIGEN 72-4

• Gastrointestinal, lung, and ovarian CA



CARCINOEMBRYONIC ANTIGEN (CEA)

• First of the carcinoembryonic proteins

discovered by Gold and Freedman

• Originally thought to be specific for colorectal

cancer but turned out to be nonspecific

marker



CHROMOGRANIN A

• Is a major soluble protein of the chromaffin

granule , a cathecolamine-storage vesicle

• Can be released from the adrenal medulla,

together with cathecolamines, on stimulationof the splanchnic nerve



CHROMOGRANIN A

• Useful marker of exocytotic sympathoadrenal

activity in patients with pheochromocytoma

• Also elevated in patients with peptide-

producing tumors, endocrine pancreatictumor, carcinoid tumors, and small cell lung

cancer

LIPID ASSOCIATED SIALIC ACID IN PLASMA



LIPID-ASSOCIATED SIALIC ACID IN PLASMA

(LASA-P)

• Sialic acids (N-acetylneuraminic acids) are the

acylated derivatives of neuraminic acid and

the terminal residues at the nonreducing end

of the carbohydrate chains in manyglycoproteins, glycolipids, and proteoglycans





(LASA-P)

• Sialoglycoproteins on the tumor cell surface

have a long history of association with

invasiveness and metastases





(LASA-P)

• Is also altered in leukemia, lymphoma,

Hodgkin’s disease, and melanoma, as well as

in nonmalignant inflammatory diseases

SQUAMOUS CELL



SQUAMOUS CELL

CARCINOMA ANTIGEN (SCCA)

• Highest in patients with metastases

• 50% of patients with renal failure

• More than 70% of patients with advanced

cervical cancer

• More than 90% of patients with recurrent

disease

• Elevated in some nonmalignant conditions



ESTROGEN RECEPTOR (ER)

• Is a protein that is localized in the nuclei of

mammary and uterine tissues

• A transcription factor that, on binding to DNA,

activate DNA and modulate specific geneexpressions

• Measurement in the breast tumor cytosol is used to

identify those patients most likely to benefit fromendocrine therapy



PROGESTERONE RECEPTOR (PgR)

• Is a member of superfamily of ligand-activated

nuclear transcription factors and is composed

of specific domains involved in DNA,

hormone-binding, and transactivation• Detected in the human as 2 distinct proteins

of different MWs (94 and 120 kD)



PROGESTERONE RECEPTOR (PgR)

• More sensitive indicator than ER of potential

responsiveness to endocrine therapy

• When patients were positive for both ER and

PgR, almost 80% responded to varioushormonal therapies

• 60% in patients positive for ER only



HER-2/Neu

• Human Epidermal Growth Factor Receptor 2

• Neu, ErbB-2, CD340, p185

• Overexpression of this gene plays a role in

pathogenesis and progression of aggressive

breast cancer



Methods

Documents

Tumor Markers for Students