Tumor markers in Oncology.

1. TUMOUR MARKERS IN
ONCOLOGY

2. WHAT ARE TUMOR MARKERS?
⦁ Tumor markers are substances that are produced by
cancer or by other cells of the body in response to
cancer or certain benign (noncancerous) conditions.
⦁ Most tumor markers are made by normal cells as well
as by cancer cells; however, they are produced at much
higher levels in cancerous conditions.
⦁ These substances can be found in the blood, urine,
stool, tumor tissue, or other tissues or bodily fluids of
some patients with cancer.
⦁ Most tumor markers are proteins.
⦁ Patterns of gene expression and changes to DNA have
also begun to be used as tumor markers.

3. THE IDEAL TUMOR MARKER
⦁ High sensitivity and very high disease specificity
⦁ Specific production by premalignant or malignant
tissue early in the progression of disease
⦁ Produced at detectable levels in all patients with a
specific malignancy
⦁ Expression in an organ site-specific manner
⦁ Evidence of presence in bodily fluids obtained
noninvasively or in easily accessible tissue
⦁ Levels related quantitatively to tumor volume
⦁ Relatively short half-life, reflecting temporal changes
in tumor burden and response to therapy
⦁ Existence of a standardized, reproducible assay that
is widely available at a reasonable cost.

4. CLASSIFICTION OF TUMOR MARKERS

5. TUMOR MARKERS
Tumor derived markers Tumor associated markers
Originate from neoplastic cells Originate from cells other than
malignancy in response to tumors
Eg. steroids from adrenocortical
tumors
Eg. Liver produce acute phase
protein in response to tumors
Can arise from tumor stroma
Eg. Hypercalcemia factors from
breast cancers
Produced by tissue infiltration by
metastasis
Eg. Hydroxyprolin in urine in c/o
osteolytic bone metastasis

7. CLINICAL APPLICATION OF TUMOR MARKERS
1) Screening and Early detection of cancer – PSA for
prostate cancer ; AFP for HCC in endemic area
2) Diagnosis –
⮚ CA 125 strongly associated with ovarian cancer
⮚ Gastrin (gastrinoma), Insulin (insulinoma)
⮚ Calcitonin – MTC
⮚ S. AFP > 500ng/ml with cirrhosis – HCC
⮚ Brain tumors where biopsy not feasible.
3) Staging – AFP, beta-HCG, LDH for testicular
cancers
4) Determining the prognosis
⮚ CEA – colorectal cancer
⮚ Her2, ki 67 – breast cancer
⮚ AFP, LDH , B-HCG– testicular cancer

8. CLINICAL APPLICATION OF TUMOR MARKERS
5) Determining effectiveness of treatment – CEA,
Thyroglobulin, CA-125, PSA
6) Detection of recurrence on follow up
⮚ CA-125 for epithelial ovarian cancer (3 months
earlier)
⮚ PSA – prostate cancer
⮚ HCG – GTT, germ cell tumors of ovaries and testis
⮚ CEA – colorectal cancer
⮚ CA 15-3 – breast cancer
⮚ Thyroglobulin – papillary/ Follicular ca

9. RECOMMENDATION FOR ORDERING TUMOR
MARKERS
⦁ Do serial testing
⦁ Same lab
⦁ While monitoring for recurrence make sure that
the level was elevated before surgery
⦁ Consider half life while interpreting the result
⦁ Know the metabolism of tumor marker
⦁ Do panel testing than single marker

10. AFP, ΑLPHA-FETOPROTEIN
⦁ AFP is a major plasma glycoprotein produced by
the yolk sac and the fetal liver-kupffer cells
during fetal development
⦁ It is thought to be the fetal analog of serum
albumin.
⦁ Normal serum value : <15 ng/ml
⦁ T ½ : 4 to 6 days
⦁ Elevated in
⚫ High levels (>500ng/ml) – in HCC & NSGCT
⚫ Markedly incresed levels (>1000ng/ml) tumor size
3cm

11. ⦁ Tumors associated with elevated AFP
⮚ Hepatocellular carcinoma – 80% cases
⮚ Metastatic disease affecting the liver
⮚ Nonseminomatous germ cell tumors of testis - Yolk sac
tumor/ embryonal / mixed GCT
⮚ Ovarian germ cell tumors (20%) except dysgerminoma
⮚ CSF:plasma ratio of AFP > 1:40 – CNS involvement
⦁ False positive 🡪 in benign conditions causing liver
parenchymal inflammation and necrosis
⚫ Hepatitis
⚫ Pregnancy
⚫ Primary biliary cirrhosis
⚫ Extrahepatic biliary obstruction

12. ⦁ Developmental birth defects a/w elevated AFP
⚫ Omphalocele ,Gastroschisis
⚫ Neural tube defects: ↑ α-fetoprotein in amniotic fluid
and maternal serum
⚫ Ataxia : elevated AFP is used as one factor in
diagnosis
⚫ Decreased in downs syndrome

13. ⦁ For screening – can be combined with USG for
early cases of HCC in high risk areas
⦁ For follow up – normalization of levels within 25-
30 days is indicative of appropriate decline
⦁ For staging of testicular cancers along with beta-
HCG and LDH

14. CARCINOEMBRYONIC ANTIGEN (CEA)
⦁ glycoproteins involved in cell adhesion
⦁ Normally produced in GIT of fetal development
and then again raised in some cancers
⦁ Normal value : <2.5ng/ml in non-smokers
<5ng/ml in smokers
⦁ T ½ - 1-7 days

15. ⦁ CEA levels elevated in
⦁ Malignancy
⚫ Colorectal carcinoma
⚫ gastric carcinoma,
⚫ pancreatic carcinoma,
⚫ lung carcinoma,
⚫ breast carcinoma, and
⚫ medullary thyroid carcinoma
⦁ Benign
⚫ ulcerativecolitis,
⚫ pancreatitis,
⚫ cirrhosis, COPD,
⚫ Crohn's disease,
⚫ hypothyroidism
⚫ in smokers.

16. CEA
⦁ Level is incresed with
⚫ Well-differentiated tumors
⚫ Lymph node and distant metastasis
⚫ Left-sided tumors
⚫ Tumors causing bowel obstruction
⚫ Aneuploid tumors
⚫ Liver dysfunction

17. USES OF CEA
⦁ Prognosis : preoperative CEA>5ng/ml 🡪 decrease
OS
⦁ As a measure of completeness of tumor resection
⦁ Monitoring tumor recurrence after surgery
within 3-4 months even CT is normal
⦁ Monitor tumor regression in metastatic disease

18. PSA – PROSTATE SPECIFIC ANTIGEN
⦁ Glycoprotein secreted by prostate acinar and ductal
cells
⦁ PSA is produced for the ejaculate, where it
liquefies semen in the seminal coagulum and
allows sperm to swim freely
⦁ Normal value : 2.5-4ng/ml
⦁ T ½ : 2-3 days
⦁ Levels
⚫ <4ng/ml – less likely cancer
⚫ 4-10 ng/ml – benign disease (BPH, prostatitis) vs prostate
cancer
⚫ >10ng/ml - likely to be cancer
⦁ Transient increase in PSA may be after ejaculation,
catheterization, vigorous bicycle exercise

19. FREE PSA VS BOUND PSA
•Most PSA in the blood
is bound to serum
proteins
•free to total ratio < 25%
- increase cancer risk
•promising for
eliminating
unnecessary biopsies in
men with PSA levels
between 4 and 10 ng/mL.

20. USES
⦁ For screening of prostate cancer
⚫ The role is controversial : benefit of early diagnosis vs risk
of overdiagnosis and over treatment
⚫ High sensitive but less specific
⚫ US FDA has approved the PSA test for annual screening
of prostate cancer in men of age 50 and older along with
DRE
⚫ UK national health service allows patients to decide with
discussion with doctor
⦁ Risk stratification and staging
⚫ Low-risk: PSA < 10, Gleason score ≤ 6, AND clinical stage
≤ T2a
⚫ Intermediate-risk: PSA 10-20, Gleason score 7, OR
clinical stage T2b/c
⚫ High-risk: PSA > 20, Gleason score ≥ 8, OR clinical stage
≥ T3

21. ⦁ Post-treatment monitoring
⚫ Post radical prostatectomy – PSA becomes
undetectable
⚫ Failure of radiation to decrease PSA <1ng/ml – s/o
recurrence
⚫ Biochemical recurrence – when PSA level increases
on 3 consecutive testing
⚫ PSA doubling time – time required for increase in
PSA twofold
⦁ After radical prostatectomy doubling time reflects
aggressiveness of original cancer
⚫ PSA velocity
⦁ Normal – 0.04ng/ml/yr for age 60 yrs
⦁ If rapid rate of increase (>0.75ng/ml/yr or >20%) correlates
with cancer

22. PSMA – PROSTATE SPECIFIC MAMBRANE
ANTIGEN
⦁ Newer biomarker for prostate cancer
⦁ Higher values associated with early progression
and relapse
⦁ Current use is limited to PSMA scan – look for
metastasis
⦁ Can be a target for treatment
⚫ Lutetium bound to PSMA to treat the prostate cancer

23. CA - 125
⦁ Glycoprotein normally expressed in coelomic
epithelium during fetal development
⦁ Normal value : <35U/ml
⦁ T ½ : 4-5 days
⦁ Elevated in
⚫ Malignancy
1. >90% cases of advanced epithelial ovarian cancer
2. cervical endocarcinoma, Endometrial
adenocarcinoma, trophoblastic tumors of liver , lung
3. Non hodgkins lymphoma representing
pleuropericardial or peritoneal involvement
⚫ Benign : cirrhosis, Renal failure, menstruation,
endometriosis, pregnancy

24. USES
⦁ To aid in diagnosis
⚫ High levels a/w non mucinous ovarian cancer in >90%
⚫ Normal level does not exclude tumor
⚫ Can not distinguish benign and malignant pelvic mass
⚫ Values >65U/ml correlate with peritoneal involvement
⦁ To know response to treatment and follow up
⚫ Correlates with poorer prognosis if elevated 3-6 weeks
after surgery
⚫ Level >35U/ml – residual tumor
⚫ Rising level during chemotherapy – tumor progression –
precede clinical recurrence by many months

25. ⦁ For prognosis
⚫ Preoperative value >65 U/ml 🡪 poor prognosis
⚫ Post surgery – 50% decline within 5 days 🡪 good
prognosis
⚫ Normalization within 3 cycles of chemotherapy 🡪
good prognosis

26. CA 19 - 9
⦁ Blood group carbohydrate 🡪 sialylated derivative
of Lewis antigen
⦁ Synthesized by normal human pancreatic and
biliary ductal cells
⦁ Normal value : <37U/ml
⦁ elevated in
⚫ Malignancy : Pancreatic cancer (70-90%)
Colorectal cancer (20-40%)
Biliary tract cancer
⚫ Benign : pancreatitis, primary biliary tract disease ,
cirrhosis

27. C 19 - 9
⦁ Very high levels (>1000 U/ml) are often
associated with surgically unresectable lesions
⦁ Mainly used for following the pancreatic cancer
patients.
⚫ Post surgical increase concentration correlates with
recurrence

28. BETA- HCG
⦁ Placental polypeptide hormone produced by
syncytiotrophoblast
⦁ Normal value : <5mIU/ml for women
<3mIU/ml for men
⦁ T ½ :18-24 hours
⦁ Elevated in
⚫ Malignant
1. GTN (Gestational trophoblastic neoplasia) mainly
choriocrcinoma
2. Germ cell tumors of testis and ovary
⚫ Benign
1. During pregnancy / ectopic pregnancy

29. ⦁ Beta HCG used for initial diagnosis, determine
prognosis, follow up response to treatment and
detect recurrence early.
⦁ Beta HCG does not cross bloodbrain barrier ..
CSF: serum ratio >1:60, if ratio is less than this
🡪cerebral metastsis

30. CA 15-3
⦁ Glycoprotein antigen
⦁ Normal value : <25U/ml
⦁ T ½ : <2 weeks
⦁ Elevated in
⚫ Malignancy : breast cancer, pancrease, gastric,
ovarian, lung, liver cancer
⚫ Benign: chronic hepatitis, cirrhosis, sarcoidosis, TB
⦁ Used to monitor response to treatment, to detect
recurrence early in all stages of breast cancers

31. CALCITONIN
⦁ Hormone produced by parafollicular C cells of
thyroid gland
⦁ It helps to regulate blood calcium levels
⦁ Normal value : 0.2-25 pg/ml
⦁ T ½ : 12 min
⦁ Eleveted in
⚫ Malignancy: medullary thyroid carcinoma
lung cancer
⚫ Benign : thyroid nodules
⦁ Used for diagnosis of MTC – basal calcitonin <25
pg/ml or calcium stimulated <100 pg/ml

32. CHROMOGRANIN A AND NEURON SPECIFIC
ENOLASE (NSE)
⦁ Normal value : <76ng/ml in men
<51ng/ml in women
⦁ Elevated in
⚫ NET(neuroendocrine tumors)
⚫ Carcinoid tumors
⚫ Neuroblastoma
⚫ Small cell lung cancer
⚫ Pancreatic islet cell tumor

33. CONCLUSION
⦁ Tumor markers have changed the diagnosis and
management of patients with malignancy
⦁ Important role in screening of prostate cancer,
staging testicular cancer, prognosis in colorectal
cancer
⦁ Evaluated for screening of HCC, epithelial
ovarian neoplasia
⦁ Newer genetic markers are introduced

34. Thank you….