Part 1

cancer progression

• Proliferation

• Transformation

• Invasion

• Metastasis

• Vacularization

activation of oncogenes

Cancer Progression Factors

• e.g., Ras protiens

upregulation of proteases

Cancer Progression Factors

• e.g., MMPs (Matrix metalloproteinases)

  • Enzyme released by your cancer cells that will breakdown the tissue for it to metastasize.

deactivation of adhesion molecules

Cancer Progression Factors

• e.g., E-cadherin

stimulation of angiogenesis genes

Cancer Progression Factors

• e.g, VEGF

  • these are the ones that are simulated if you have poor lifestyle

mutation of DNA

Cancer Progression Factors

• e.g, p53, BRCA1, cyclins

  • Probably because of an infection or autoimmune disease

loss of tumor suppressor genes

Cancer Progression Factors

• e.g, pRb, APC

growth factor dysregulation

Cancer Progression Factors

• e.g, EGF, HER2/neu

  • These are normally low levels in a healthy individual, but when there is cancer, they are elevated

stage 1

Cancer Staging and Progression (4)

• Localized primary tumor

  • Can still be removed.

stage 2

Cancer Staging and Progression (4)

• Cancer cells release MMP

• Invasion of primary tumor through epithelium and into blood vessels

stage 3

Cancer Staging and Progression (4)

• Migration of tumor into regional lymph nodes

stage 4

Cancer Staging and Progression (4)

• Metastasis and invasion of tumor to distant tissues

tumor markers

• Produced directly by the tumor or as an effect of the tumor on the host

  • Note: these are not automatically associated with malignancy, it can be present in certain benign tumors, and can also be present in normal physiological processes.

types of tumor markers

1. serum proteins (β2-microglobulin)

2. oncofetal antigens (AFP, CEA)

• Genes that are developed during pregnancy, malignancy in non-pregnancy.

3. hormones (calcitonin, β-hCG)

4. carbohydrate epitopes/cancer antigens (CA-125)

5. receptors (estrogen receptors, Her-2/neu)

6. enzymes (ALP)

PSA

Applications of Tumor Marker Detection

• Screening

  • Biopsy Indication

HPLC

• Best method of choice for catecholamine tumor markers like HVA, 5HIAA, metanephrines and VMA?

• commonly used for detection of small molecules (e.g. endocrine antibodies)

  • catecholamines and metabolites: carcinoid tumors, pheochromocytoma and neuroblastoma

IHC

• Best method of choice for Receptor tumor markers like estrogen, progesterone receptor etc. It uses Biopsy as specimen.

immunoassay

Laboratory Consideration

• Most commonly used method to measure tumor markers

  • But they require some considerations;

  • 1. Since there is a wide range of values for out tumor markers

  • 2. Lack of standardization

linearity

Immunoassay

• Determined by analyzing specimens spanning the reportable range

• “Linear range” span of analyte concentrations over which a linear relationship exist between the analyte and signal

hook effect

Immunoassay

• Excessively high tumor marker concentration can result in falsely low measurements

• “antigen excess:”

Note: There will be a hook effect of your graph if there is no ZOE or undiluted.

heterophile antibodies

Immunoassay

• Human anti-mouse Abs (HAMAs)

Note: They are given to patients with auto-immune diseases

• This Abs has to be tested first if the patient develops cancer. That is why it is also important to note for the px history

  • Because if the px was given these HAMAs before, these Abs binds to the latex beads = FALSE NEGATIVE.

analytical interferences

Immunoassay

• Icterus

• Lipemia

• Hemolysis

• Antibody cross reactivity

Neuroblastoma