INTERPRETATION OF LABORATORY TESTS

CRPTUMOR MARKERS

SERUM FERRITIN

Dr. Jyothi Reshma S

C-reactive protein

• Acute phase reactant - liver• Binding to C polysaccharide of Pneumococcus• Tillet and Francis 1930• Pentraxin – 23kDa• T ½ 19hours• Raised in infections, inflammatory disorders

and malignancies

Activation of complement – classical pathway IL6, IL1, TNFαHelps in opsonisation

Glucocorticoids ++Insulin --

• Normal < 0.3mg/dL• Clinically significant >1mg/dL• <1 : increasing age, low level of physical

activity, vigorous exercise, obesity, pregnancy, sleep deprivation, depression, insulin resistance, DM, seizures

INFECTIONS MALIGNANCY• High at onset: bacterial• Rise on day 3-4:

superimposed bacterial infection

• Elevated in systemic fungal infection – immunocompromised

• Marker of sepsis – 300mg/dL

• Ca lung, liver, skin, kidney, bladder, lymphoma, leukaemia

• Tumor necrosis and local tissue damage ++ CRP

• Opsonization and removal of tumor cells

Inflammatory disorders• Evaluation- extent or severity of inflammation• Monitoring- disease activity• Prognostic value• RA: 2-3 (moderate)to >10 (severe) – synovitis, erosions,

normal in 40%• SLE: serositis, synovitis ++• PMR, GCA: CRP > ESR, GCA with vison loss - CRP• Still’s disease, vasculitis, ankylosing spondylitis, erosive

OA, gout, reactive arthritis, sarcoidosis, scleroderma, PsA• Inflammatory bowel disease: CD(70-100%) UC(50-60%)• Patients with ++ CRP respond better to biological therapy

Cardiovascular disease• Proatherogenic- binds to LDL-C- monocyte adhesion,

transmigration, macrophage polarization• 2013 guidelines- ACC and AHA: hs-CRP : statin therapy• 1) 40-75yr, nonDM, without clinical ASCVD, LDL C

70-189mg/dL, 5 year risk of ASCVD <5%: hsCRP ≥2- statin COR IIb, LOE C

• 2) <40/>75yr, nonDM, without clinical ASCVD, LDL C 70-189mg/dL, hsCRP ≥2- statin COR ILb, LOE C

• 3) DM without clinical ASCVD, <40/>75yr, LDL C <70mg/dL, hsCRP ≥2- statin COR ILb, LOE C

ASCVD: atherosclerotic cardiovascular disease COR: class of recommendation LOE:level of evidence

• CRP: 0.7 – 0.9: 22 wk till delivery, 1.3: onset of labor

• Higher levels – 1st TM, early 2nd TM: preterm delivery

TUMOR MARKERS

Biomolecules secreted by cancer cells – diagnosis, treatment response, early recognition of recurrenceOncofetal antigens: AFP, CEATumor associated antigen: CA125, CA 19-9, CA 15-3, CA72-4Hormones: beta-HCG, PSA, calcitoninEnzymes: LDH, PAP, NSE, PLAP, TDTSerum and tissue proteins: beta-2 microglobulin, GFAP, ferritin, FDP

AFP (Alpha-feto protein)

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Liver, germ cell cancer of ovaries or testes

• Also elevated during pregnancy

• Help diagnose, monitor treatment, and determine recurrence

• Blood

B2M (Beta-2 microglobulin)

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Multiple myelomaand lymphomas

• Crohn's disease and hepatitis

• Determine prognosis

• Blood

CA 15-3 (Cancer antigen 15-3)

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Breast cancer and lung, ovarian

• Also elevated in benign breast conditions

• Stage disease, monitor treatment, and determine recurrence

• Blood

CA 19-9 (Cancer antigen 19-9)

• CANCERS

• WHAT ELSE?

WHEN/HOW USED

USUAL SAMPLE

• Pancreatic, sometimes colorectal and bileducts

• Pancreatitis and inflammatory bowel disease

• Stage disease, monitor treatment, and determine recurrence

• Blood

CA-125 (Cancer antigen 125)

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Ovarian

• endometriosis, some other benign diseases

• Help diagnose, monitor treatment, and determine recurrence

• Blood

Calcitonin

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Thyroid medullary carcinoma

• pernicious anemia and thyroiditis

• Help diagnose, monitor treatment, and determine recurrence

• Blood

CEA (Carcino-embryonic antigen

• CANCERS

WHAT ELSE?

WHEN/HOW USED

• USUAL SAMPLE

• Colorectal, lung,breast, thyroid, pancreatic, liver, cervix, and bladder

• hepatitis, COPD, colitis, pancreatitis, and in cigarette smokers

• Monitor treatment and determine recurrence

• Blood

Chromogranin A (CgA)

• CANCERS

WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Neuroendocrine tumors (carcinoid tumors, neuroblastoma)

• May be most sensitive tumor marker for carcinoid tumors

• To help diagnose and monitor

• Blood

Estrogen receptors

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Breast

• Increased in hormone-dependent cancer

• Determine prognosis and guide treatment

• tissue

hCG (Human chorionic gonadotropin)

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Testicular and trophoblastic disease

• Elevated in pregnancy, testicular failure

• Help diagnose, monitor treatment, and determine recurrence

• Blood, urine

Her-2/neu

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Breast• Oncogene that is

present in multiple copies in 20-30% of invasive breast cancer

• Determine prognosis and guide treatment

• Tissue

Monoclonal immunoglobulins• CANCERS

• WHAT ELSE?

• WHEN/HOW USED

• USUAL SAMPLE

• Multiple myeloma and Waldenstrom’s macroglobulinemia

• Overproduction of an immunoglobulin or antibody, usually detected by protein electrophoresis

• Help diagnose,monitor treatment, and determine recurrence

• Blood, urine

Progesterone receptors

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Breast

• Increased in hormone-dependent cancer

• Determine prognosis and guide treatment

• Tissue

PSA (Prostate specific antigen), total and free

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED

• USUAL SAMPLE

• Prostate

• benign prostatic hyperplasia, prostatitis and with age

• Screen for and help diagnose, monitor treatment, and determine recurrence

• Blood

Thyroglobulin

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Thyroid

• Used after thyroid is removed to evaluate treatment

• Determine recurrence

• Blood

BTA (Bladder tumor antigen)

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Bladder

• Not widely available, but gaining acceptance

• Help diagnose and determine recurrence

• Urine

CA 72-4 (Cancer antigen 72-4)

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Ovarian

• No evidence that it is better than CA-125 but may be useful when combined with it; still being studied

• Help diagnose• Blood

Des-gamma-carboxy prothrombin • CANCERS

• WHAT ELSE?

• WHEN/HOW USED

• USUAL SAMPLE

• Hepatocellular carcinoma (HCC)

• New test; often used along with an imaging study plus AFP and/or AFP-L3% to evaluate if someone with

• To evaluate risk of developing HCC; to evaluate treatment; to

• Blood

NMP22 (nuclear matrix protein)

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Bladder

• Not widely used

• Help diagnose and determine recurrence

• Urine

Prostate-specific membrane antigen (PSMA)

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Prostate

• Not widely used; levels increase normally with age

• Help diagnose• Blood

Prostatic acid phosphatase (PAP)

• CANCERS

• WHAT ELSE?

• WHEN/HOW USED • USUAL SAMPLE

• Metastatic prostate cancer, myeloma, lung cancer

• Not widely used anymore; elevated in prostatitis and other conditions

• Help diagnose

• Blood

SERUM FERRITIN

• Ferritin – iron storage protein• Iron sequestration – ferroxidase- Fe2+ to Fe3+• Ferritin captures and buffers intracellular iron

pool• Normal – 50-200µg/L

• Low- <12 – iron depletion• Elevated : iron overload, acute inflammatory

conditions, liver disease, alcohol excess• Iron overload: primary: hemochromatosis,

wilson’s disease ; secondary: transfusion overload, excess dietary iron, PCT, ineffective erythropoiesis

High serum ferritin without iron overload

Liver disease (NASH), viral hepatitisAlcohol excess, chronic inflammatory conditions (RA/IBD)Bacterial infections, malignancyThyrotoxicosis Familial hyperferritinemia and cataract syndrome

• Acute phase reactant : inflammatory conditions

• ++ : increaded risk of MI and CAD• Prognostic marker : allogenic stem cell implant

THANK YOU