Clinical Application of Tumor Markers · Clinical Application of Tumor Markers ... ¾Predictive...

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)

QUESTIONS????

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