Tumour markers in clinical practice

1. TUMOUR MARKERS IN
CLINICAL PRACTICE
PRESENTER:
DR SWDWAMSHREE BORO,
PGT 2ND YEAR,
DEPARTMENT OF
MEDICINE,
AMCH
MODERATOR:
DR RIMA MONI DOLEY,
ASSOCIATE PROFESSOR,
DEPARTMENT OF
MEDICINE,
AMCH

2. What is cancer?
 Uncontrolled cell division
 Invasion of surrounding &
distant tissues
 Oldest description: 3000
BC Egypt

3. EPIDEMIOLOGY
 In 2021, the number of people diagnosed with
cancer was ~1.9 million
• Men: 9,70,250
• Women: 9,27,910
 Mortality was ~ 6,08,570

4. WHAT ARE TUMOUR MARKERS?
 A/ the National Cancer Institute, anything present in
or produced by cancer cells or other cells of the body
in response to cancer or certain benign (non
cancerous) conditions that provides information
about a cancer, such as how aggressive it is, what
kind of treatment it may respond to, or whether it is
responding to treatment.

5.  Found in:-
1. Blood
2. Urine
3. Stool
4. Tumours, or other tissues
5. Bodily fluids

6. IDEAL TUMOUR MARKER
 Highly sensitive & highly specific
 Detectable at early stage of tumour
 Produced at detectable levels in all patients with a specific
malignancy
 Show positive correlation with tumour volume & extent
 Short half life- allowing early prediction of complete response
& survival during chemotherapy.
 Should have an inexpensive, simple, standardised automated
assay with clearly defined reference limits

7. CLASSIFICATION
 CIRCULATING TUMOUR
MARKERS
 Blood, urine, stool, bodily
fluids
 Uses:
1. Estimate prognosis
2. Determine tumour stage
3. Detect residual cancer
after treatment or one that
has returned post
treatment
4. Assess & monitor the
effect of treatment
 TISSUE TUMOUR MARKERS
 Found in tumours
 Uses:
1. Diagnose, stage, classify
cancer
2. Estimate prognosis
3. Select targeted therapy

8.  Eg of circulating tumour markers:
• Calcitonin for Medullary thyroid cancer
o Measured in blood
o Use-
1. treatment response
2. Screen for recurrence
3. prognosis
• CA125 for ovarian cancer
o Measured in blood
o Uses-
1. Treatment effectivity
2. recurrence

9. BIOMARKERS
 Tissue tumour markers that indicate whether
someone is a candidate for a particular targeted
therapy. Eg:
1. Estrogen & progesterone receptor- to determine
whether breast cancer patients should get treatment
with hormone therapy
2. FGFR3 gene mutation analysis- to determine
treatment for bladder cancer patients.

11. TUMOUR MARKERS CANCER NON NEOPLASTIC
CONDITIONS
HORMONES
HCG GTD, Gonadal GCT Pregnancy
Calcitonin Medullary cancer of thyroid
Catecholamines Pheochromocytoma
ONCOFETAL ANTIGENS
AFP HCC, Gonadal GCT Cirrhosis, hepatitis
CEA Adenocarcinoma of colon,
pancreas, lung, breast, ovary
Pancreatitis, hepatitis,
IBD, smoking
ENZYMES
Prostatic acid phosphatase Prostate cancer Prostatitis, prostatic
hypertrophy
Neuron specific enolase SCC lung, neuroblastoma
LDH Lymphoma, Ewing’s sarcoma Hepatitis, haemolytic
anaemia

12. TUMOUR MARKERS CANCER NON NEOPLASTIC
CANCER
TUMOUR ASSOCIATED PROTEINS
PSA Prostate cancer Prostatitis, prostatic
hypertrophy
Monoclonal immunoglobulin Myeloma Infection, MGUS
CA 125 Ovarian cancer, some
lymphomas
Menstruation, peritonitis,
pregnancy
CA 19-9 Colon, pancreatic, breast
cancer
Pancreatitis, ulcerative colitis
CD 30 Hodgkin’s disease,
anaplastic large cell
lymphoma
CD 25 Hairy cell leukaemia, adult T
cell leukaemia/ lymphoma
Haemophagocytic
lymphohistiocytosis

13. CLINICAL APPLICATION
 Screening – identify subclinical disease
 Diagnosis- cancer diagnosis
 Staging
 Prognosis- estimate survival outcomes
 Prediction - therapeutic response
 Monitoring therapy: tumour shrinkage & cancer
recurrence
 Preventive- risk prediction

14. Role in screening
 Cons:
1. Lack of sensitivity- for early invasive disease or
premalignant lesions
2. Lack of specificity- for malignancy
Thus leading to low positive predictive values in
screening asymptomatic populations

15. Table 1: Biomarkers in screening asymptomatic subjects of cancer
MARKER MALIGNANCY
FOBT Colorectal cancer
PSA Prostate cancer
CA 125 Ovarian cancer
VMA/ HVA Neuroblastoma
AFP HCC
Pepsinogen Gastric cancer
HCG GTD (in previous hydatidiform
mole patients)

16. Role in diagnosis
 Not a key diagnostic tool. Complementary to clinical
finding & medical imaging as:
1. Can also be elevated in benign conditions
2. Not elevated in early stages of the disease
3. Many are not specific to a particular type of cancer
4. Level of a TM can be elevated by more than 1
type of cancer

17. Role in staging or prognosis
 Prognostic markers are most important in cancers
that vary widely in their outcomes. Eg- Prostate or
breast cancer
 Helps identify patients with aggressive disease that
could benefit from additional therapies & those who
may not require it

18. Table 2: Markers for determining prognosis in different
cancers
CANCER MARKERS
Breast Oncotype DX,* Upa/ PAI-1
Germ cell AFP, HCG, LDH
Colorectal CEA, MSI
Prostate PSA
Ovarian CA 125
*Urokinase type plasminogen activator & plasminogen activator inhibitor

19. Role in monitoring & recurrence
 Monitor patients with advanced cancer receiving
systemic therapy
 Decreasing TM levels following initiation of therapy
 Tumour regression
 Increasing TM
 Progressive disease

20. Table 3: Tumour markers used in monitoring therapy in different
cancers
Cancer Marker
Colorectal CEA
Hepatocellular AFP
Pancreatic CA 19-9
Ovarian CA 125
Breast CA 15-3
Prostate PSA
Differentiated thyroid Thyroglobulin

21. • However tumour markers should not be used alone
in assessing response to therapy
• There might be transient increase within first few
weeks of administering therapy due to tumour cell
necrosis or apoptosis in response to the initial
treatment with chemotherapy

22. RECENT ADVANCES
 Develop biomarkers that can distinguish aggressive early
stage cancers from slow growing ones that would not cause
symptoms - to reduce overtreatment
 New procedures for measuring tumour markers will focus on:
1. Gene expression microarray
2. Proteomics
3. Detection of circulating tumour cells

23. REFERENCES
 Harrison Internal Medicine 21st edition
 Duffy MJ. Tumor markers in clinical practice: a review focusing
on common solid cancers. Med Princ Pract. 2013;22(1): 4-11.
doi: 10.1159/000338393. Epub 2012 May15. PMID:
22584792; PMCID: PMC5586699
 www.cancer.gov
 Laboratory Medicine Practice Guidelines- Use of tumour
markers in testicular, prostate, colorectal, breast, and ovarian
cancers