Clinical Application of Tumor Markers
F N DADGAR MD CLINICAL ONCOLOGIST
BOUALI HOSPITALAZAD UNIVERSITY
Definition
• Analytic ValidityAnalytic Validity• Clinical validity• Clinical UtilityClinical Utility
Diagnostic markerPredictive markerPredictive markerPrognostic marker
List of Tumor markersList of Tumor markers
• Alpha‐fetoprotein (AFP)Alpha fetoprotein (AFP)• Cancer types: Liver cancer and Germ cell tumorstumors
• Tissue analyzed: Blood• How used: To help diagnose liver cancer and follow response to treatment; to assess stage, prognosis, and response to treatment of germ cell tumors
i l b li ( )Beta‐2‐microglobulin (B2M)Cancer types: Multiple Myeloma ,yp p y ,chronic lymphocytic leukemia, and some lymphomassome lymphomas Tissue analyzed: Blood, urine, or cerebrospinal fluidHow used: To determine prognosis andHow used: To determine prognosis and follow response to treatment
B h h i iBeta‐human chorionic gonadotropin (Beta‐hCG)gonadotropin (Beta hCG)Cancer types: Choriocarcinoma and testicular cancer Tissue analyzed: Urine or bloodTissue analyzed: Urine or bloodHow used: To assess stage, prognosis, and response to treatmenttreatment
BCR ABL f iBCR‐ABL fusion geneCancer type: Chronic myeloid yp yleukemia(CML)(CML)Tissue analyzed: Blood and/orTissue analyzed: Blood and/or bone marrowHow used: To confirm diagnosis and monitor disease statusand monitor disease status
BRAF mutation V600ECancer types: Cutaneousmelanoma and colorectal cancermelanoma and colorectal cancerTissue analyzed: TumoryHow used: To predict response to t t d th itargeted therapies
CA15 3/CA27 29CA15‐3/CA27.29
Cancer type: Breast cancerTi l d Bl dTissue analyzed: BloodHow used: To assess whether treatment is working or disease h dhas recurred
CA19‐9Cancer types: Pancreatic cancerCancer types: Pancreatic cancer, gallbladder cancer, bile duct cancer, and gastric cancerTissue analyzed: BloodTissue analyzed: BloodHow used: To assess whether treatment is working
CA 125CA‐125Cancer type: Ovarian cancerypTissue analyzed: BloodH d T h l i di iHow used: To help in diagnosis, assessment of response to ptreatment, and evaluation of recurrence
CalcitoninCancer type: Medullary thyroidCancer type: Medullary thyroid cancerTissue analyzed: BloodH d T id i di iHow used: To aid in diagnosis, check whether treatment is working, and assess recurrence
Carcinoembryonic antigen (CEA)Cancer types: Colorectal cancerCancer types: Colorectal cancer and breast cancerTissue analyzed: BloodHow used T h k h th l t lHow used: To check whether colorectal cancer has spread; to look for breast cancer recurrence and assess response to treatment
CD20Cancer type: Non HodgkinCancer type: Non‐Hodgkin lymphomaTissue analyzed: BloodHow used: To determine whetherHow used: To determine whether treatment with a targeted therapy g pyis appropriate
Chromogranin A (CgA)Cancer type: NeuroendocrineCancer type: Neuroendocrine tumorsTissue analyzed: BloodH d T h l i di iHow used: To help in diagnosis, assessment of treatment response, p ,and evaluation of recurrence
Cytokeratin fragments 21 1Cytokeratin fragments 21‐1Cancer type: Lung canceryp gTissue analyzed: BloodH d T h l i it iHow used: To help in monitoring for recurrence
EGFR mutation analysisyCancer type: Non‐small cell lung cancerTissue analyzed: TumorTissue analy ed: TumorHow used: To help determine
dtreatment and prognosis
Estrogen receptor (ER)/progesterone receptor (PR)(ER)/progesterone receptor (PR)Cancer type: Breast cancerTissue analyzed: TumorHow used: To determine whetherHow used: To determine whether treatment with Hormonal therapy is appropriate
HE4Cancer type: Ovarian cancerTissue analyzed: BloodTissue analyzed: BloodHow used: To assess disease progression and monitor for recurrence
HER2/neuHER2/neuCancer types: Breast cancer, gastric yp , gcancer, and esophageal cancerTi l d TTissue analyzed: TumorHow used: To determine whether treatment with Traztuzumab is
iappropriate
KITCancer types: GastrointestinalCancer types: Gastrointestinal stromal tumor and mucosal melanomaTissue analyzed: TumorTissue analyzed: TumorHow used: To help in diagnosing and determining treatment
KRAS mutation analysisCancer types: Colorectal cancerCancer types: Colorectal cancer and non‐small cell lung cancerTissue analyzed: TumorHow used: To determine whetherHow used: To determine whether treatment with a particular type of p yptargeted therapy is appropriate
Lactate dehydrogenaseCancer type: Germ cell tumorsCancer type: Germ cell tumors,Lymphoma , y pTissue analyzed: BloodH d T tHow used: To assess stage, prognosis, and response to p g , ptreatment
Nuclear matrix protein 22Nuclear matrix protein 22Cancer type: Bladder cancerTissue analyzed: UrineHow used To monitor response toHow used: To monitor response to treatment
Prostate‐specific antigen (PSA)Cancer type: Prostate cancerTissue analyzed: BloodTissue analyzed: BloodHow used: To help in diagnosis, p g ,assess response to treatment, and l k flook for recurrence
ThyroglobulinThyroglobulinCancer type: Thyroid canceryp yTissue analyzed: TumorH d T l t tHow used: To evaluate response to treatment and look for recurrence
21‐Gene signature (Oncotype DX)21‐Gene signature (Oncotype DX)Cancer type: Breast cancerTissue analyzed: TumorHow used: To evaluate risk ofHow used: To evaluate risk of recurrence
70‐Gene signature (Mammaprint)70‐Gene signature (Mammaprint)Cancer type: Breast cancerTissue analyzed: TumorHow used: To evaluate risk ofHow used: To evaluate risk of recurrence
R l t PRegulatory Process
• Combination Level of Evidence score• Combination Level of Evidence score• Needs a molecular insight to Cancer
Tumor Marker Utility Grading System Le els of E idenceLevels of Evidence
• Category 1: Based upon high‐level evidence, there is uniform NCCN consensus that the intervention is appropriate
• Category 2A: Based upon lower‐level evidence, there is uniform NCCN consensus that the intervention is appropriate.appropriate.
• Category 2B: Based upon lower‐level evidence, there is NCCN consensus that the intervention is appropriate. C t 3 B d l l f id th i• Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
Molecular testing approved in lcommon malignancies
• GliomaGlioma• BreastC l• Colon
• Prostate• Lung
CHALLENGESCHALLENGES
CHALLENGES
• References:References:
‐National Cancer Institute (NCI)NCCN (WWWNCCN org)‐NCCN (WWW.NCCN.org)
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