L19 Tumor markers and Tutorial Flashcards
List characteristics of an ideal tumor marker. (5)
- High sensitivity and high specificity
- Organ-specific
- Discriminatory to identify tumor from benign states
- Correlate with mass, stage, prognosis
- Short half-life
Which of the following is incorrect?
A. PSA can be used for population-based screeening for CA prostate
B. AFP is good for screening for high risk groups e.g. Hep B carreirs for HCC
C. CA 125 can aid diagnosis of CA ovaries
D. Serial CEA can be used for diagnosis of CRC
E. In CA breast, ER/PR in anti-estrogen therapy and HER2 in transtuzumab can be used for prediction of treatment response
D
- Serial CEA is for monitoring of treatment response and detection of recurrence/relapse
The normal range of AFP?
Any circumstances with elevated AFP in healthy individuals?
Normal range: <10 mcg/L
CA if > 1000
Pregnancy! <500 mcg/L
Newborn! >10000 mcg/L > normalized in 1 year
Clinical use of AFP (when is AFP elevated)?
Benign: acute or chronic hepatitis, cirrhosis
Malignant: HCC, hepatoblastoma, NSGCT (non-seminomatous germ cell tumor) (together with HCG, LDH)
Where can CEA be found? (Carcinoembryonic antigen)
GI tract, breast, head and neck, lung
What is the normal range of CEA?
It is for the screening of CRC - T/F?
Normal < 3mcg/L (non-smoker); <5 mcg/L (smoker)
Benign conditions rarely >10 mcg/L
NOT for screening CRC
What is the clinical use of CEA (when is CEA elevated)?
Benign : IBD, cirrhosis
Malignancy: CRC, CA stomach, lung (not elevated in some CA lung!)
Clinical uses of HCG (human chorionic gonadotrophin)? (3)
- Early pregnancy: urine HCG
- Trophoblastic disease: Hydatidiform moles
- Germ cell tumor (e.g. choriocarcinoma) > placenta
Which of the following about HCG is incorrect?
A. It may be interfered by analytic interferences like heterophile Ab
B. The half life of HCG is around 5-7 days
C. Non-pregnant women (premenopause): <1 IU/L
D. Post-menopausal women: <7 IU/L
E. Men: < 2 IU/L
B
- t1/2: should be 36-48 hours
Clinical use for PSA (when will PSA be elevated)? (9)
Malignant
- CA prostate
Non-malignant
- BPH
- Prostatitis
- UTI
- urinary obstruction
Preanalytical factors
- Urological manipulation: TURP (Transurethral resection of the prostate)
- DR examination
- Prostate massage
- Ejaculation
- Invasive procedures (prostate biopsy, cystoscopy, transrectal USG, etc.)
Which of the following about PSA is correct?
A. Normal value is <4 ug/L
B. there is an age-specific range
C. Protstate health index (PHI) can improve the diagnostic performance of PSA
D. PPV (positive predicted value) of traditional PSA cutoff >4 ug/L is only 30%, meaning that only 30% of +ve cases are true +ve (elevated PSA).
E. % free pSA, p2PSA, PSA velocity and denisity can improve the diagnostic performance of PSA
All of the above
Clinical use of Cancer Antigen 125 (CA 125)?
- Epithelial ovarian Ca
- Primary Peritoneal CA
- Benign: endometriosis, pleural effusion
How CA 125 is measured to lower any analytical interference?
It can be used to assess adnexal mass (lump around uterus) together with other markers and USG such as?
Test is done during 1st half of menstrual cycle (CA 125 increases during menses)
Other markers: ROMA, RMI
Canter antigen 15-3 clinical use? (2)
How many times the cutoff represents metastasis?
- CA breast, lung, GIT, liver
- Benign: breast, liver disease
5x
Thyroglobulin clinical use? (2)
- It is considered together with [anti-Tg]
- Stimulated Tg or suppressed
- CA thyroid
- Thyrotoxicosis factitia (caused by exogenous TH)
What tumor marker for screening NPC at the asymptomatic stage?
Plasma EBV DNA
Which of the following about AFT is correct?
A. AFT is used for screening in asymptomatic patients
B. AFT is recommended for cancer screening in the general population
C. AFT is a useful marker for liver metastasis
D. Serum AFT is measured together with serum HCG and LDH to diagnosis and stage non-seminonatous germ cell tumros
E. AFT will not be elevated in infants.
Only D is correct
E: DDx of elevated AFP levels for infants (1st year) Congenital disorders - Neural tube defects - Down's syndrome - Trisomy 18 - Congenital nephrosis
Childhood
- Hereditary tyrosinemia
- Citrin deficiency
- Ataxia telangiectasia
- NSGCT
- Hepatoblastoma
- HCC
Tutorial: Patient 32 years old, HBV carrier with mild deranged liver function, hyperbilirubinemia, elevated ALP and ALT and elevated AFP (100).
What are the possible causes of deranged liver function? (5) (examples)
- Liver cirrhosis
- Acute/ chronic hepatitis
- Partial biliary obstruction
- Alcoholic liver disease
- Drug-induced (paracetamol, isoniazid, methotrexate, tetracycline, azathioprine…)
Tutorial: Patient 32 years old, HBV carrier with mild deranged liver function, hyperbilirubinemia, elevated ALP and ALT and elevated AFP (100).
How to interpret the AFP results?
- Hep B carrier, at risk of HCC.
- Other than HCC, can also be due to cirrhosis, acute/chronic hepatitis, biliary tress obstruction etc.
- Transient increase may occur in chronic liver iseases
- Another serum AFP sample should be taken 2 weeks afterwards
- Raised serum AFT at single time point should be be relied on its own to diagnose cancer. Changes in levels over time would be more clinically useful.
Tutorial: Patient 32 years old, HBV carrier with mild deranged liver function, hyperbilirubinemia, elevated ALP and ALT and elevated AFP (100).
How to follow up the patient?
- Liver USG (Hepatobiliary system) > look for SOL, cirrhotic changes, biliary obstruction
- Serial monitoring of LFT, AFP in 2-4 weeks
(AFP has half-life of ~ 5days)
*AFT > 200 ug/L is suggestive of HCCC + USG liver lesion > 2cm
AFT >400ug/L diagnostic of HCC
62-year-old woman presents with 6-week history of change of bowel habit and intermittent blood and mucous in her motions. Also complains tenesmus in last 2 weeks.
Weight loss of 2-3kg during the preceding 3 months.
CEA is 15.
What is the interpretation of this data?
What is the likely diagnosis?
15 is higher than normal
normal for non-smoker: <3; smoker: <5 ug/L
Likely diagnosis: Rectal cancer
What are the possible causes of elevated serum CEA level? Can serum CEA be used for cancer screening?
Elevated:
Non-malignant: IBD, cirrhosis, peptic ulcers, bronchitis, emphysema, colonic polyps
Malignant: CRC, CA lung, stomach, pancreas, breast, ovaries
- Cannot be used for CRC screening because it is non-specific (but used for monitoring progression of cancer)
62-year-old woman presents with 6-week history of change of bowel habit and intermittent blood and mucous in her motions. Also complains tenesmus in last 2 weeks.
Weight loss of 2-3kg during the preceding 3 months.
CEA is 15.
If CEA cannot give a definitive diagnosis of cancer, what should be done?
What is the clinical use of CEA then?
Histological examination of a biopsy of a lesion
- Pre-treatment CEA level correlates with disease burden and may be of prognostic value (as the baseline)
- used for post-treatment surveillance at least in the first 3 years after primary tumor resection
- CEA levels should return to baseline after resection
- Elevated CEA levels ~ recurrence
Patient with hypercalcemia, elevated urea and creatinine, elevated TP and supressed albumin = reversed A:G ratio. What initial investigations to do next? (7)
Probable diagnosis? (1)
- Serum protein electrophoresis
- PTH level
- Urine protein electrophoresis (Bence Jones protein)
- Serum Ig pattern to determine paraprotein clone e.g. elevated IgG/A/M > monoclonal increase (MM)
- Serum free light chain (kappa/lambda)
- CBC
- Skeletal survey (bone lesions)
Multiple myeloma
What is the diagnostic test for Multiple myeloma?
(2) What to look for?
Bone marrow biopsy - look for clonal plasma cell proliferation
54 year old lady with fatigue, generalized edema, signs and symptoms of heart failure.
P/E shows hepatomegaly. Also complained of pain, numbness, tingling sensations over thumbs and fingers.
Urine and creatinine elevated, Low albumin, raised bilirubin and ALP, elevated ALT.
24 hour urine total protein = 4.7g/day
SPE: IgG lamda paraprotein band of 19.0g/L was detected at gamma region
Renal biopsy: Apple-green birefringence on polarized light examination with Congo red histological staining.
EM: ultrastructural appearance of amyloid fibrils.
Likely diagnosis?
Amyloid light chain (AL) amyloidosis (primary amyloidosis)
- extracellular tissue deposition of fibrils composed of low molecular weight subunits of normal serum proteins
- antiparallel beta-pleated sheet configuration > characteristic appearance on EM:
1. Ability to bind to Congo red > green birefringence under polarized light
2. Thioflavine T (yellow-green fluorsence)
WIKI:
*The disease is caused when a person’s antibody-producing cells do not function properly and produce abnormal protein fibers made of components of antibodies called light chains. These light chains come together to form amyloid deposits which can cause serious damage to different organs
What complications has the patient likely been suffering from? (4)
54 year old lady with fatigue, generalized edema, signs and symptoms of heart failure.
P/E shows hepatomegaly. Also complained of pain, numbness, tingling sensations over thumbs and fingers.
Urine and creatinine elevated, Low albumin, raised bilirubin and ALP, elevated ALT.
24 hour urine total protein = 4.7g/day
SPE: IgG lamda paraprotein band of 19.0g/L was detected at gamma region
- Nephrotic syndrome with proteinuria
- Restrictive cardiomyopathy
- Peripheral neuropathy (carpel tunnel syndrome)
- Hepatomegaly with elevated liver enzymes
Treatment modalities to decrease the production of pathologic free light chain in AL light chain amyloidosis?
(list 3/6)
- Corticosteroids
- Cytotoxic therapy (chemo)
- High dose melphalan (chemo)
- Autologous hematopoietic stem cell transplant
- Proteasome inhibitors (bortezomib)
- Immunomodulatory drug (lenalidomide)
Biochemical tests to monitor hematological response and organ response after treatment in AL light chain amyloidosis?
- Serum free light chain ratio
- Serum and urine protein electrophoresis and immunofixation
- Cardiac marker (NT-proBNP/cardiac troponin)
- Plasma creatinine and eGFR
- 24-hour urine protein
- Plasma ALP
AL amyloidosis fibrils are composed of fragments of monoclonal light chains. Affected patients may have amyloidosis a/w with other plasma cell dyscrasias, such as?
Multiple myeloma Waldenstrom macroglobulinemia (IgM paraprotein, V. viscous)
