CC - Tumor Markers

non-communicable diseases

also lifestyle-related disease (LRD)

1. tobacco use

2. unhealthy diet

3. insufficient physical activity

4. harmful use of alcohol

risk factors of non-communicable disease:

1. heart disease/stroke

2. cancer

3. diabetes

4. chronic lung/respiratory disease

non-communicable diseases:

1. lung

2. liver

3. colon/rectum

4. prostate

5. stomach

6. leukemia

cancer among filipino men:

1. breast

2. cervix

3. lung

4. colon/rectum

5. ovary

6. liver

cancer among filipino women:

tumor

swelling; growth; non-cancerous or cancerous

malignant

cancer that has tendency to spread or return after surgical removal

benign

non malignant; non-cancerous

metastasis

traveling of disease from one part of body to another; spreading of tumor

cancer

disease caused by uncontrolled growth of cells that form new solid mass/tumor and may spread to other areas of body; malignant tumor of any type

neoplasm

new solid mass/tumor

tumorigenesis

tumor formation; complex combination of inherited and acquired genetic mutations

angiogenesis

development of new BV to supply oxygen and nutrients to cells

apoptosis

programmed cell death

neoplasm

synonymous w/ “tumor”; uncontrolled tx growth; cancerous or non-cancerous

neoplasm

from Greek “new formation”

oncogenes

cancer causing genes; encodes protein that when mutated promotes uncontrolled cell growth

tumor suppressor gene

encodes protein involved in protecting cells from unregulated growth

cell cycle

phases of cell activity divided into growth (G), DNA synthesis (S), and mitosis (M)

onco-

prefix indicating relationship to tumor

-oma

suffix; tumor/swelling; usually benign

oncogenic

substance that stimulates late tumor formation

carcinogen/ic

any substance that stimulates formation of cancer

carcinoid

cancer-like tumor; not as malignant as true cancer

adeno-

tumor in which cell arrangement resembles gland like structure

adenocarcinoma

cancer originating in gland/organ and very common form of cancer; usually rapid spreading

adenosarcoma

malignant tumor containing both gland and CT

squamous cell carcinoma

originates in squamous epithelium

1. type of cancer

2. tumor size

3. histology

4. regional lymph node involvement

5. metastasis

factors determining cancer severity:

1. primary site of origin

2. histological classification

3. by grade

4. by stage

cancer can be classified by:

1. carcinoma

2. sarcoma

3. myeloma

4. leukemia

5. lymphoma

6. mixed type

histological classification:

carcinoma

cancer derived from lining cells of organs; can occur at almost any structure in body

sarcoma

malignant tumor made up of CT such as bone, muscle, fat, cartilage, etc.

osteosarcoma

malignant tumor of bones

chondrosarcoma

malignant tumor of cartilage

leiomyosarcoma

malignant tumor of smooth muscles

rhabdomyosarcoma

malignant tumor of skeletal muscles

mesothelial sarcoma/mesothelioma

malignant tumor of membranous lining of body cavities

fibrosarcoma

malignant tumor of fibrous tissue

grade I

well differentiated cells; slight abnormality

grade II

cells are moderately differentiated and slightly more abnormal

grade III

cells are poorly differentiated and very abnormal

grade IV

cells are primitive and undifferentiated

1. tumor size and involvement/invasion of nearby tissue

2. regional lymph node involvement

3. metastasis

TNM staging:

Tx

tumor cannot be evaluated

Tis

carcinoma in situ

T0

no signs of tumor

T1-4

size and/or extension of primary tumor

Nx

lymph nodes cannot be evaluated

N0

tumor cells absent from regional lymph nodes

N1

regional lymph nodes metastasis present (near origin)

N2

tumor spread to extend b/w N1 and N3; not used at all sites

N3

tumor spread to more distant or numerous regional lymph nodes

M0

no distant metastasis

M1

metastasis to distant organs; beyond regional lymph nodes

stage I cancer

localized primary tumor

stage II cancer

invasion of primary tumor through epithelium and into BV

stage III cancer

migration of tumor into regional lymph nodes

stage IV cancer

metastasis and invasion of tumor to distant tissues

1. proliferation

2. transformation

3. invasion

4. metastasis

5. vacularization

cancer progression:

1. cell cycle and DNA repair genes

2. loss of tumor suppression genes

3. growth factor dysregulation

4. activation of oncogenes

5. upregulation of proteases

6. deactivation of adhesion molecules

7. stimulation of angiogenesis genes

mutations in cancer progression:

screening

biopsy indication

PSA

tumor marker for screening

diagnosis

high levels indicative of disease

1. metanephrines

2. HVA/VMA

3. PRL

4. PTH

5. chromogranin A

6. cortisol

7. ACTH

tumor marker for diagnosis:

prognosis

high levels = poor; receptor status used for indication of chemotherapy

1. B2-microglobulin

2. CA-125

3. CEA

4. LD

5. Her-2/neu

6. ER

7. PR

tumor markers for prognosis:

1. CA-125

2. CA 19-9

3. CEA

4. AFP

5. hCG

6. PSA

7. SPE

tumor markers for monitoring treatment:

tumor markers

biomarker in blood/tissue and elevated is linked to cancer

tumor markers

produced directly by tumor or as effect of tumor

tumor markers

expressed in very low levels in blood

tumor markers

not useful in diagnosis; but useful in tumor staging, monitoring therapeutic responses, predicting px outcomes and detecting cancer recurrence

1. tumor specific

2. absent in healthy individuals

3. measured easily/readily available

4. high analytical sensitivity/specificity

5. cost-effective

6. results contribute to px care & outcome

characteristics of tumor markers:

1. serum proteins

2. oncofetal antigens

3. hormones

4. metabolites

5. receptors

6. enzymes

biomolecules that can be tumor markers:

oncofetal antigen

protein produced during fetal development; elevated in cancer; correlated w/ tumor burden, useful for monitoring success of therapy

B2-microglobulin

found on surface of all nucleated cells; used as nonspecific marker of high cell turnover common in tumors

B2-microglobulin

used in hematologic malignancies; multiple myeloma, immunoglobulins

hormone

valuable in diagnosing neuroblastoma

oncofetal antigens

expressed transiently during normal development and turned on again after formation of tumors

receptors

to classify tumors for therapy

1. estrogen and progesterone receptors

2. growth factors

used to choose b/w endocrine and cytotoxic therapy:

endocrine therapy

typically more effective in px w/ ER and PR (+) px

tamoxifen

example of endocrine therapy

1. PSA

2. LD

3. ALP

4. NSE

enzyme tumor markers:

prostate specific antigen (PSA)

tumor type: prostate cancer screening

clinical utility
therapy monitoring
recurrence

IA

method for PSA

lactate dehydrogenase (LD)

tumor type: hematologic malignancies
clinical utility: prognostic indicator; elevated in nonspecific cancer

EA

method for LD

alkaline phosphatase (ALP)

tumor type:

metastatic bone carcinoma
HCC
osteosarcoma
lymphoma
leukemia

alkaline phosphatase (ALP)

clinical utility:
determination of liver and bone involvement
nonspecific elevation in bone and liver cancers

EA

method of alkaline phosphatase (ALP)

neuron specific enolase (NSE)

tumor type: neuroendocrine tumor

clinical utility:
prognostic indicator
monitoring disease progression

IA

method for NSE

1. serum M-protein

2. serum-free light chain

3. B2-microglobulin

serum protein tumor markers:

1. serum M-protein

2. serum-free light chains

tumor type: plasma cell dyscrasias

clinical utility:
diagnosis
therapeutic monitoring

1. serum protein electrophoresis (SPE)

2. immunofixation electrophoresis (IFE)

methods for serum M-protein:

IA

method for serum-free light chains

B2-microglobulin

tumor type: hematologic malignancies
clinical utility: prognostic marker for lymphoproliferative disorders

IA

method for B2-microglobulin

1. ACTH

2. ADH

3. C-peptide

4. calcitonin

5. chromogranin A

6. cortisol

7. gastrin

8. GH

9. homovanillic acid (HVA)

10. 5-hydroxyindoleacetic acid (5-HIAA)

11. metanephrines

12. PTH

13. PRL

14. vanillylmandelic acid (VMA)

endocrine tumor markers:"