TUMOUR MARKERS IN CLINICAL PRACTICE PRESENTER : DR SWDWAMSHREE BORO, PGT 2 ND YEAR, DEPARTMENT OF MEDICINE, AMCH MODERATOR : DR RIMA MONI DOLEY, ASSOCIATE PROFESSOR, DEPARTMENT OF MEDICINE, AMCH
What is cancer? Uncontrolled cell division Invasion of surrounding & distant tissues Oldest description: 3000 BC Egypt
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
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.
Found in:- Blood Urine Stool Tumours, or other tissues Bodily fluids
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
CLASSIFICATION CIRCULATING TUMOUR MARKERS Blood, urine, stool, bodily fluids Uses: Estimate prognosis Determine tumour stage Detect residual cancer after treatment or one that has returned post treatment Assess & monitor the effect of treatment TISSUE TUMOUR MARKERS Found in tumours Uses: Diagnose , stage, classify cancer Estimate prognosis Select targeted therapy
Eg of circulating tumour markers: Calcitonin for Medullary thyroid cancer Measured in blood Use- treatment response Screen for recurrence prognosis CA125 for ovarian cancer Measured in blood Uses- Treatment effectivity recurrence
BIOMARKERS Tissue tumour markers that indicate whether someone is a candidate for a particular targeted therapy. Eg : Estrogen & progesterone receptor- to determine whether breast cancer patients should get treatment with hormone therapy FGFR3 gene mutation analysis- to determine treatment for bladder cancer patients.
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
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
CLINICAL APPLICATION Screening – identify subclinical disease Diagnosis- cancer diagnosis Staging Prognosis- estimate survival outcomes P rediction - therapeutic response Monitoring therapy: tumour shrinkage & cancer recurrence Preventive- risk prediction
Role in screening Cons: Lack of sensitivity- for early invasive disease or premalignant lesions Lack of specificity- for malignancy Thus leading to low positive predictive values in screening asymptomatic populations
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)
Role in diagnosis Not a key diagnostic tool. Complementary to clinical finding & medical imaging as: Can also be elevated in benign conditions Not elevated in early stages of the disease Many are not specific to a particular type of cancer Level of a TM can be elevated by more than 1 type of cancer
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
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
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
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
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
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: Gene expression microarray Proteomics Detection of circulating tumour cells
REFERENCES Harrison Internal Medicine 21 st 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