Lecture 8 Flashcards

(40 cards)

1
Q

What are tumor specific markers

A
  • made only by tumor cells - cancer specific
    -not a definitive test best used with conjuction
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2
Q

What are tumor associated markers

A

found in many cancers but elevated when in presence of malignancy

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3
Q

What characteristics make a tumor marker ideal

A

Specificity
sensitivity
practicality

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4
Q

Why is specificity important in tumor markers

A

-should be produced only by malignant cells and not normal tissues = lower chance of false positive
-elevated levels are directly linked to cancer = reduces risk of misinterpretation
-able to correctly identify pts without the disease (true neg)

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5
Q

Why is sensitivity important in tumor markers

A
  • should be elevated in ALL patients with tumor = able to detect at ANY age even if isnt visible on imaging
    -able to correctly identify pts with disease (true post)
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6
Q

Why is practicality important in tumor markers

A
  • needs to be easily measurable and cost effective
    -test should be non invasive , need minimal volume and produces results quickly
    -marker levels must be reproducible and stable across various labs
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7
Q

What are the limitations of tumor markers

A

Lack of 100% sensitivity and specificity
- no tumor exists that is both 100% sensitive and specific
-some are elevated in conditions that arent cancer = false negative

Challenges in early detection
-marker may not be elevated in early stages = hard to detect until the disease is progressed
CA19-9 increased in v late pancreatic cancer

Overlap among different cancers
-not specific for just one type of cancer ; reduces diagnostic value

CA125 - increased in ovarian cancer but also endometriosis, liver disease and benign conditions

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8
Q

What is clinical sensitivity

A
  • proportion of true positives that a test can correctly identify

Example- CEA for monitoring colorectal cancer increased 60-70 % in those with metastatic colorectal cancer and 10% in early stage

meaning CEA is not sensitive enough to be used as a screening tool for early stage detection (low = many ppl missed)

FOT is good as screening test with colonoscopy

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9
Q

What is clinical specificity

A
  • how to correctly identify those who dont have the disease (true neg)
    -how well the test is able to distinguishes between healthy and sick
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10
Q

What is a challenge for specificity

A

False positive
-test says you have something when you dont
-can cause unnecessary follow up tests, anxiety and extra treatment

like CA 125 that is increased in different types of cancers

tumor markers with low specificity should not be used as primary screening tools must be used with another treatment imaging , biopsy

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11
Q

high sensitivity but low specificity can show

A

-pts with disease (low false negative) but it can also cause ( false positives)

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12
Q

high specificity but low sensitivity can lead to

A

can miss patients who have the disease - false negatives

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13
Q

What is the choice of test for early detection

A

tests with high sensitivity

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14
Q

What is the choice of test for diagnosis confirmation or monitoring

A
  • tests with high specificity
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15
Q

What type of tests should screening prioritize

A

tests with high sensitivity
-early detection important for improving outcomes detects most cases even at risk of false positives

Fecal Occult Blood Test (FOBT) for colorectal cancer screening and
mammograms for breast cancer

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16
Q

What type of tests should Diagnosis and Monitoring prioritize

A

once cancer is suspected or diagnosed
test should be specific enough to rule out false positives , confirm diagnosis and monitor recurrence

CEA for colorectal cancer, PSA for prostate cancer, and CA-125 for ovarian cancer.

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17
Q

What are the limitations of sensitivity and specificity

A

must be done in conjunction with clinical history , imaging and other lab tests
need a multifaceted approach

18
Q

What are the primary roles of tumor markers

A

screening, prognosis and
staging, monitoring treatment, and detecting recurrence.

19
Q

What is screening

A

to test asymp patients to detect potential cancer

tumor markers are used on high risk populations instead of gen pop

20
Q

What are high risk populations and why are tumor markers good to be used for them

A

–good to be used on a population with increased risk of developing certain cancers

PSA- men over 50
CA125 - women with history of ovarian cancer

21
Q

What are some challenges with screening with tumor markers

A

Low prevalence in gen pop
-using tumor markers in gen pop when rate of cancer is low can cause false positive

Lack of specificity
tumor markers are not specific to one cancer type can be increased in benign conditions
PSA increased in non cancer prostate conditions like BPH

-reason why tumor markers cant be used as standalone screening tools

22
Q

prognosis vs staging

A

prognosis - outcome of disease - likeihood
tumor markers can be related to size

-staging - extent of spread in the body

-AFP in HCC, high levels large tumor size, and increased degree of invasion
-CA19-9
-CYFRA21-1

23
Q

How are TM able to monitor the effectiveness of the
treatment

A

Establishing a baseline
-measuring TM before start of treatment to get a baseline so changes can be tracked

Post treatment
-early intervention
TG after thyroidectomy = undetectable
CEA- to monitor response to chemo in colorectal cancer
PSA- monitors prostate cancer

therapeutic adjustments
-TM can help adjust treatment

24
Q

What is the role of tumor markers in Detecting Recurrence

A

TM can rise before any physical symptoms

AFG and hCG in testicular cancer
-serial monitoring to detect recurrence before imaging or physical

Long term surveillence
even after youre “cancer free”

25
what are oncofetal AG
found in fetal tissues but reexpressed in malignany cells
26
What is AFP cancers associated with it application limitations
-produced by liver and yolk sac in fetal time -low in adult life increased in Hepatocellular Carcinoma (HCC) = large or advanced tumor most common liver cancer increased in Germ cell tumor like testicular cancer used to monitor growth tumor and treatment in hepatocellular carcinoma and germ cell tumours. increased AFP = recurrence limitation - AFP elevated in benign liver diseases cirrhosis, hepatitis
27
What is hCG cancers associated with it application limitations
-produced by placenta -increase in non preggos = malignancy -increased in gestational trophoblastic disease, molar pregnancy , choriocarcinoma increased in Testicular germ cell tumours, particularly seminomas and non-seminomatous tumours in men -used to monitor response in testicular cancer and gestational trophoblastic disease -decrease = positive therapeutic response limitation - increased in non cancer conditions like pregnancy needs careful interpretation ,
28
Cancers Associated with CEA application limitations
CEA - produced during fetal development not present in healthy adults -elevated in many cancers = good tumor marker Colorectal Cancer:- diagnose, stage and monitor increased in advanced Lung and Liver Cancers: used to monitor and detect recurrence of colorectal cancer but can be increased in smoking and inflammatory diseases NOT a good screening tool limitation increased in chronic inflammation, smoking, or age, which limits its specificity as a screening tool.
29
CA125 application limitations
Carbohydrate antigens (CA)- found on surface of cancer cells found increased in specific cancers = good for diagnosing and monitoring CA125 -found on surface of ovarian cancer celsl increased in Ovarian cancer especially in advanced stages; critical in monitoring and detecting recurrence -increased in endometrial cancer not as specific -used for monitoring chemotherapy response in pts with ovarian cancer -used for monitoring of recurrence - limitation seen in benign conditions like endo, PID, periods
30
CA19-9 application limitations
-increased in malignancies of GIT -Increased in pancreatic cancer, -monitors tumor burden and response -Increased in gastric, liver, and colorectal cancers. -used to monitor treatment response and recurrence limitation increased in benign conditions, such as pancreatitis and cholecystitis
31
CA15-3 application limitations
increased in Metastatic or advanced breast cancer -monitors treatment response and detects recurrence limitations will not be increased in early conditions
32
B2M application limitations
-found on surface of cells lymphs, tumour cells Increased in multiple myeloma = correlated with burden and prognosis Increased in CLL helps to assess progression -used to monitor disease activity Limitation increased in renal insufficiency
33
Vanillylmandelic Acid (VMA) and Homovanillic Acid (HVA) application limitations
VMA and HVA are catecholamines (epinephrine and norepinephrine) increased in neuroblastoma 90% : highly sensitive levels decrease after treatment specimen - 24 hour urine tested with HPLC
34
Sample type for tumor markers
serum or plasma serum better for markers not bound to blood cells Plasma better for markers affected by cellular components like hormone assays
35
timing of sample for tumor markers
-serial sampling must be consistent -needed to monitor the trend in marker levels
36
storage conditions for tumor markers
- can degrade over time if not stored proper refrigerate - 2-8C to be analyzed in 24 hours freeze -20 or -80 to preserve marker integrity follow manufacturer protocol
37
immunoassay
most common method to test -need AB to bind to AG (markers) enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), or chemiluminescent immunoassays
38
potential interferences
-affects accuracy HAMA can form complexes with reagents can lead to false positive or false neg -occurs when pts are exposed to monoclonal AB therapy or with autoimmune disease. Their immune system produces AB against mouse AB hemolysis (red cell destruction) lipemia (excess fat) bilirubin all affect accuracy
39
What is high dose hook effect
artefact in immunoassays when there is high conc of tumor marker in a sample -causes falsely low measurement of TM as assay is saturated -causes misinterpretations -solution is to dilute
40
what should a person do if they undergoing derial monitoring but they change labs
- establish a baseline with new lab