CLINICAL CHEMISTRY 2 Characteristics of an ideal Tumor Marker

 Specificity for a single type of cancer

TUMOR MARKER - Substance should only be produced by
the tumor.
Learning Objectives:
 High sensitivity
 Know the ideal characteristics of a
- Small growth or metastasis produces
tumor marker.
measurable amount of marker.
 Understand the role of tumor markers
 Correlation of marker level with tumor
for diagnosis and management of
size
patients with cancer.
 Homogeneous (i.e., minimal post-
 Know the emerging technologies for
translational modification)
tumor markers.
 Short half-life in circulation so that when
 Understand the role of tumor markers
production drops, the level of marker
for therapeutic selection.
falls off rapidly, producing low or
TUMOR or NEOPLASM undetectable concentration.
- Uncontrolled proliferation of cells.
(refers to the tissue that are growing Types of Tumor Markers
uncontrollably/very fast ang growth.
Normally your cells grow in size by mitosis)  hCG
Hormones  Calcitonin
 Benign – confined (encapsulated)  gastrin; prolactin
- Adenoma  acid phosphatase
Enzymes  alkaline phosphatase
 Malignant – capable of metastasis
 PSA
(it invade other organs of the body)
Cancer  CA125
- Carcinoma – epithelial in origin antigen  CA15.3
Ex. Adenocarcinoma (gland) proteins &  CA19.9
- Sarcoma – mesenchymal in origin glycoproteins
Ex. Osteosarcoma
Metabolites  norepinephrine
Rules for Tumor Markers  epinephrine
 Determine risk (PSA) Normal  Immunoglobulin
Proteins  Glycoproteins
 Screen for early cancer (calcitonin,
 carcinoembryonic or
occult blood) oncofetal)
 Diagnose a type of cancer (hCG, Oncofetal  CEA
catecholamines) antigens  AFP
 Estimate prognosis (CA125)  Estrogen
 Predict response to therapy (CA15-  Progesterone
3, CA125, PSA, hCG) Receptors  Androgen
 Monitor for disease recurrence or  Corticosteroid
progression (most widely used Genetic  Mutations/translocations,
changes etc.
function)
 Therapeutic selection (her2/neu,
kras).
 Tumor Markers in routine use Other companion diagnostic test
Marker Cancer Barrett et al. Clin Chem 2013;59:198-201
CA15-3, BR 27.29 Breast Biomarker Drug Cancer
CEA, CA 19-9 Colorectal Cancer
CA 72.4, CA 19-9, Gastric  Her2.neu  Trastuzumab Breast ca.
 KRAS  Cetuximab Colorectal
CEA  BRAF  Panitumumab Melanoma
NSE, CYFA 21.1 Lung  ALK Fusion  Vemrafeni Non-small cell lung
PSA, PAP Prostate  EGFR  Crizotinib ca.
  Non-small cell lung
CA 125 Ovarian BCL-ABL Gefitinib, erlotinib
ca.
Calcitonin, Thyroid translocation  Imatinib, dasatinib
Chronic myeloid
 nilotinib
thyroglobulin Leukemia
hCG Trophoblastic
CA 19-9, CEA Pancreatic
AFP, CA 19-1 Hepatocellular
BAP, Osteocalcin, Bone
NTx RT-PCR for circulating tumor cell
Catecholamines, Pheochromocytoma  Prostate Cancer – PSA, PSMA
metabolites
 Breast Cancer – Cytokeratin 19, CEA,
Fecal occult blood Colon cancer
MUC1, hMAM
Genetic tumor markers and disease  Melanoma – Tyrosinase, MART1,
MAGE3, GAGE
Oncogenes: activated by mutation
Mechanism for circulating tumor cells
– N-ras: leukemia
– K-ras: colon/ gastric  Metastatic Cascade Cells grow as
– C-erB-2: Breast/gastric benign tumor Cells break through
– N-myc: Breast/Neuro the basement membrane Travel
– c-abl/bcr: CML through the blood Adhere to capillary
– bcl-2: leukemia/lymp wall Escape from blood vessel
– HER-2/INT2/ATM/ H-ras: Breast (extravasation) Proliferate to form
– MCC: colon metastases.

Tumor Suppressors: loss of the gene Cancer genomics examples

leads to proliferation and metastasis Cancer Associated Inheritanc
gene e mode
– p53: Breast/colon/lung Breast and BRCA1, Dominant
– RB1: Retinoblastoma Ovarian BRCA2
– WT1& 2: Renal Cancer
– BRCA1& 2: Breast/ pancreas/Ovarian Wilm’s tumor WT1 Dominant
– BRCA1:prostate/stomach Familial RB1 Dominant
– APC: Colorectal retinoblastoma
– MTS1: Melanoma
Huntington’s Huntingtin Dominant
– DCC: colon/gastric
Disease
Hereditary MLH1, Recessive
colorectal MSH2,6,
cancer PMS1,2
 Xeroderma Recessive
Skin Cancer pigmentosum
XPB, XPD,
XPA