TUMOUR MARKERS ( TM ) IN THE DIAGNOSIS, MANAGEMENT AND FOLLOW UP OF MALIGNANT DISEASES B y A B D U L L A H I T A S I ' U A H M A D ( U 1 5 M D 2 6 )
OUTLINE Introduction C l a s s i f i c a t i o n o f T M C h a r a c t e r i s t i c s of an ideal T M Clinical usefulness of T M C o m m o n TM in use Conclusion
INTRODUCTION A tumor marker is a substance produced by a tumor or by the host in response to tumor It is used to differentiate a tumor from normal tissue. By mearsurement in blood or secretions
C L A S S I F I C A T I O N O F T M U N C O F E T A L P R O T E I N S A l p h a f e t o p r o t e i n , C E A , P a n c r e a t i c o n c o f e t a l A g , T i s s u e p o l y p e p t i d e a n t i g e n . M U C I N E G L Y C O P R O T E I N S C A - 1 2 5 , C A - 19 - 9 , CA - 15 - 3 , CA - 27 - 29 E N Z Y M E S A N D I S O E N Z Y M E S P S A , Neurones s p e c i f i c e n o l a s e , G l y c o s y l t r a n s f e r a s e , P l a c e n t a l a l k a l i n e p h o s p h a t a s e , L D H , C K H O R M O N E S A C T H , A D H , H C G , H P L , P T H , C a l c i t o n i n .
C L A S S I F I C A T I O N C O N T . . . R E C E P T O R S O e s t r o g e n - r , Progestin - r , Her 2 - r . D N A M A R K E R S B R C A - 1 a n d B R C A - 2 . S E R U M A N D T I S S U E P R O T E I N S B 2 - M i c r o g l o b i n , M o n o c l o n a l i m m u n o g l o b u l i n / p a r a p r o t e i n O T H E R S
CHARACTERISTICS OF AN IDEAL TM 1 I t m u s t b e s p e c i f i c t o a p a r t i c u l a r t i s s u e o r t u m o u r 2 I t m u s t b e s e c r e t e d i n t o t h e b l o o d , u r i n e o r o t h e r b o d y f l u i d s 3 I t m u s t h a v e p o t t e n t i a l f o r e a r l y d e t e c t i o n a n d m o n i t o r i n g o f t h e t u m o u r
C O N T . . . 4 T h e h a l f l i f e m u s t b e s h o r t 5 I t m u s t b e a b l e t o i n d i c a t e t h e p r e s e n c e o f t h e t u m o u r b e f o r e c l i n i c a l m a n i f e s t a t i o n . 6 I t m u s t b e 1 % s e n s i t i v i t y a n d s e n s i t i v i t y
Clinical usefulness of tumour markers Screening populations at risk Not all tumor markers are good screening tools Diagnosis Use results from markers, imaging, risk factors, and symptoms Prognosis Concentration of the marker determines prognosis
Uses contd... Detection of recurrence Once tumor is removed, elevations of marker can indicate regrowth Monitoring response to treatment Decreased levels of tumor marker indicate therapy is working Increased levels of tumor marker may indicate need for a change to therapy
C O M M O N T M IN USE
1- PROSTATE-SPECIFIC ANTIGEN (PSA) PSA is a glycoprotein produced by the epithelial cells of the acini and ducts of the prostatic ducts in the prostate A marker for prostate cancer Has a half life of 3 days Probably function to liquefy semen Two circulating forms: free and complexed
PSA contnd ….. Serum level raised in;- Prostate cancer BPH Prostatitis Rectal examination Urinary retention Sexual intercourse
PSA contnd ….. Levels varies with age, higher in adults Reference range in adults is 0-4µg/l PSA is useful in the management of prostate cancer i.e for;- Screening and early diagnoses of the disease Differential diagnoses Staging of a tumour Evaluation of tumour volume Monitoring of therapeutic efficacy
PSA contnd ….. The major limitation of PSA is that it is not cancer specific Values overlap in BPH & prostate cancer Concentration of bound PSA is higher in prostate cancer & that of free PSA is higher in BPH
PSA contnd ….. Differentiation between BPH and prostate cancer using PSA can be done using the following;- PSA Density ;- defined as total serum PSA concentration /prostate volume Normal individuals and in BPH it is usually <0.15 In patients with prostatic cancer, values of 1.7 or even higher are obtained
PSA contnd ….. 2. PSA Velocity ;- defined as rate of PSA increase over time Atleast 3 PSA measurements are need. The rate of increase of > 0.75µg/L/year is suggestive of prostate cancer.
PSA contnd ….. 3. PSA Index ;- This is the % of the total plasma PSA that is free An index of to 2 5 % ,suggestive of BPH An index of <2 5 %,suggestive of prostate cancer
Introduction: hCG is a hormone normally secreted by trophoblasts in the placenta during pregnancy It is a glycoprotein consisting of a nd Half life of 12-20hrs Non-tumor elevation seen in pregnancy, cirrhosis and IBD. 2- HUMAN CHORIONIC GONADOTROPIN ( hCG )
Clinical Applications: Detection and follow-up of gestational trophoblastic diseases (GTDs) GTDs include: Hydatiform mole Invasive mole Choriocarcinoma It is also elevated in nonseminomas testicular cancers hCG , continued…
Introduction: Oncofetal antigen Abundant serum protein normally synthesized by the fetal liver and yolk sac Re-expressed in certain types of tumors Half life of 5 days Normal value is less than 10µg/l In pregnancy >10µg/l 3. α - Fetoprotein ( AFP)
Clinical Applications: Diagnosis, prognosis, and treatment monitoring of hepatocellular carcinoma ( >1000µg/l) Also elevated in hepatitis and cirrhosis(<200µg/l) AFP is not completely specific for HCC AFP can be used in conjunction with ultrasound every 6 months in patients at high risk of developing HCC AFP continued…
OTHER TUMOR MARKERS Carcinoembryonic antigene : an oncofetal , marker for colorectal Ca Carbohydrate antigenes : CA 125(ovarian Ca), CA 15-3(breast Ca),CA 19-9(pancreatic Ca) β 2 -microglobulin : A marker for MM , H L . A lso increases in chronic inflammation and viral hepatitis. Immunoglobulin: Monoclonal immunoglobulin used as marker for MM
CONCLUSION Tumour markers are diverse and heterogenic but form a valuable tool in confirming diagnosis of a malignant disease, monitoring response to treatment and detection of recurrence. Newer markers are developed with research. T here is NO tumor marker that is used alone in diagnosis!
A K N O W L E G E M E N T S P r o f . A l i y u D r . R Yusuf Dr . Adamu
R E F E R E N C E S C l i n i c a l B i o c h e m i s t r y 6 t h e d i t i o n , M a r t i n A . C r o o k . C l i n i c a l c h e m i s t r y , D r ( B r i g ) M N C h a t t e r j e a L e c t u r e n o t e o f D r . Jibril .