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Tumour markers Flashcards

1
Q

What makes a good tumour marker?

A
  • Detectable only when tumour is present
  • Sensitive enough to detect small tumours at early stage of the disease
  • Be specific for certain types of malignancy
  • Correlate with amount of malignant tissue present
  • respond rapidly to tumour size

High sensitivity and specificity

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2
Q

What is a tumour marker?

A

Measurable analyte produced by a tumour which can help to diagnose the disease, provide prognostic information, identify correct treatment and monitor treatment

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3
Q

When are tumour markers primarily used?

A

Best used in post-treatment follow up but can be used throughout the diagnosis process

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4
Q

What is the problem with using tumour markers in screening?

A
  • Need to be detected early to limit spread and improve outcomes
  • Currently no marker acceptable for population screening in UK. Too many flase positives (low specificity)
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5
Q

Example of tumour marker used in screening

A

Targeted screening in genetic linked disease such as BRCA1 and BRCA2 in breast cancer

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6
Q

Why do tumour markers be poor prognostic tools?

A

Ideally need 100% specificity and sensitivity, but current markers arent near that

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7
Q

How are tumour markers used in prognois?

A

If the tumour load is related to tumour marker then a survival estimate can be made

  • e.g HCG and AFP prognostic indicators of testicular teratoma
  • e.g. P53, E-cadherin, nm23H1 and MMP-2 used together to predict outcome of node negative breast cancer
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8
Q

How are markers used in treatment?

A

Receptors used in treatment

- e.g. HER-2 positive breast cancers can be treated with herceptin

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9
Q

What is required to monitor therapy using tumour markers?

A

A quantative relationship between tumour burden and tumour marker levels.

  • Assess efficacy of treatment
  • Detection of drug/chemo resistance and response
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10
Q 
Match half life to response
A. No change
B. Improvement 
C. Response 
D. Complete response
  1. Tumour marker < 10% T0 value
  2. Tumour marker within RR
  3. Tumour marker <50% T0 value
  4. Tumour marker >50% T0 value
A

A4
B3
C1
D2

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11
Q

What are the different types of tumour markers?

A

General - nonspecific markers of analytes

Functional markers

Classical tumour markers

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12
Q

State some general tumour markers? and the tumour associated?

A
  • calcium- Hypercalcaemia in malignancy
  • ESR - inflammation
  • Sodium - mineralocorticoid excess (Conns)
  • LDH - cellular/tissue damage
  • beta(2) microglobulin: can be used for severity+spread of multiple myeloma and some lymphomas, alsso present in crohns and hepatits
  • ALP- bone/liver metastases
  • Phosphate - PTHrP effect on phopshate excretion
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13
Q

What are some functional tumour markers?

A 
Pituitary
- prolactin, ACTH, GH, TSH
Parathyroid
- PTH
Adrenal cortex
- Aldosterone, cortisol
Adrenal medullary 
- Catecholamines, metabolites 
Ovary
- Oestrogen, testosterone 
GI tract
- insulin, glucagon, VIP, gastrin, 5HIAA
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14
Q

Functional tumour markers of adrenal cortex

A

Cortisol

Aldosterone

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15
Q

Functional tumour markers of parathyroid

A

PTH

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16
Q

Functional tumour markers of pituitary

A

Prolactin
ACTH
GH
TSH

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17
Q

Functional tumour markers of adrenal medulla

A

Catecholamines

Metabolites

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18
Q

Functional tumour markers of ovary

A

Oestrogen

Testosterone

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19
Q

Functional tumour markers of GI tract

A

Insulin, glucagon
VIP, Gastrin
5HIAA

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20
Q

What is the most common pituitary tumour? symptoms?

A

Prolactinoma (benign tumour of pituitary gland)

  • Hyperprolactinaemia cause amenorrhea/infertility in females and in males ED, infertility and libido loss (prolactin inhibits GnRH)
  • Low estrogen due to high prolactin may lead to osteoporosis
  • pressure of prolactinoma on surrounding tissue manifests as headaches and vision blurs
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21
Q

What can you treat prolactinoma with?

A

Cabergoline, bromocriptine, norprolac

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22
Q

What are differnt types of cushings syndrome?

A

ACTH independent (cushings syndrome)

  • Can be due to exogenous steroids
  • or from an adrenal tumour CRH

ACTH dependent (cushings disease)

  • Pituitary adenoma secreting ACTH so feedback from cortisol is useless
  • Or ectopic ACTH secretion
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23
Q

Describe the GH excess of a tumour

A

GH excess occurs in benign pituitary tumours, cauign acromegaly in adults.
- Importantly GH is not a good diagnositic tool, but IGF-1 is more senstive so has inhert qualities of a good marker

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24
Q

How to test for GH excess?

A

Using a glucose tolerance test.

  • Patient will need to achieve hypoglycaemia and then load with glucose
  • In normal response GH secretion is inhibited in hyperglycaemia, but induced in hypoglycaemia
  • Acromegaly patients wont show this pattern

TEST MEASURES IGF-1, GLUCOSE AND GH

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25
What are medullary thyroid carcinomas?
- First neoplastic manifestation of MEN-2 - A tumour of the C-cells of the thyroid gland - high metastases rate MEN2B patients will need thyroidectomy before 6 months
26
What is the marker for MTC?
Calcitonin - secreted by C-cell hyperplasia/MTC
27
What is conns syndrome?
Primary hyperaldosteronims caused by a benign adrenal adenoma (one) or hyperplasia (both adrenal glands) - Results in low renin and high aldosterone
28
What is are phaeochromocytomas?
Tumour of the chromaffin cells in the adrenal medulla. These tumours can produce catecholamines, adrenaline and noradrenaline. - Increased secretion of catecholamines --> hypertension - Present with headaches, sweating, tachycardia, palpitations - Present after MTC in MEN syndromes - In MEN2s but no MEN1
29
What are soeme gut hormone tumours?
islet cell tumours of the pancreas - inuslinoma - glucagonoma - gastrinoma - VIPoma
30
Where do carcinoid tumours arise?
Arise from argentaffin cells of the foregut, midgut and hindgut - predominent are midgut - incidental following appendectomy
31
What is the carcionoid tumour associated with MEN?
MEN-1 foregut carcinoids
32
Match the following: 1. Foregut 2. Midgut 3. Hindgut A. small intestine, appendix, proximal large bowel B. Lungs, bronchi, stomach C. Distal large bowel, rectum
1B 2A 3C
33
What hormones can carcinoid tumours secrete?
- Seretonin - ACTH - histamine. - dopamine - substance P - neurotensin - prostaglandins - kallikrein
34
What is a carcinoid syndrome?
Caused by the release of sertonin and other vasoactive substances inot the systemic circulation - manifesting as episodic flushin, wheezing, diarrhoea and eventual righ sided valve heart disease
35
What tumours are associated with carcinoid syndrome?
Midgut carcinoid tumours, occur exclusively in the metastic setting
36
Why is diagnosing carcinoid disease early hard?
Early diagnosis looks like irritable bowel disease
37
What is a good marker for midgut carcinoids secreting serotonin? and how is it used?
5-HIAA the breakdown product of serotonin - sens 73% spec 100% - Although 5HIAA is only elevated once it has metastasized to the liver - Useful to estimate extent of disease and survival - Easily detectable in undiluted urine samples (24hr)
38
What can cause falsely elevated 5HIAA tests?
Diet - bananas, walnuts, plantain, hickory nuts, pineapple, pecans, kiwi fruit, avocados Drugs that are contained in cought/cold medicines - Acetaminophne - Guaifenesin - I-dopa (parkinsons treatment)
39
What is considered the best marker fo carcinoid tumours?
Chromagranin A is found elevated in 80-100% patients with carcinoid tumours - Blood test
40
What is a limitations to using chromagranin A to detect carcinoid tumours?
Positive results can be due to a neuroendocrine tumour | - Further testing is required for a definite diagnosis
41
State some classical tumour markers
- ADP, hCG, SP1 - CA125, CA15.3 - CEA, CA19.9 - ChA - PSA
42
What are the ACB recommendations for classical tumour markers
- Use in diagnosis and monitoring - Lab need to regularly audit their services to review requesting patterns and use - interpret results in view of clinical and lab information
43
What classical markers can be used in primary care?
PSA and CA125, but require follow up of patient being treated by secondary care
44
What are two subtypes of testicular cancer?
Seminoma 40% | Non-seminoma 60%
45
What are some classical markers of testiculare seminoma tumours?
- These produe hCG (10%), placental like ALP (50%), LDH may be raised - LDH is non-specific so might have a role in monitoring - If AFP produced elements of germ cell tumour are present which changes treatment/management
46
What are some classical markers of testiculare non-seminoma tumours?
90% produce AFP +/- hCG, where both values determine type, prognosis and therapy - Where positive are essential for monitoring response, detecting residual tumour and recurrence
47
What are some recommendations to AFP and hCG mesurements in testicular cancer?
Depends on stage and pathology but recommend AFP +/- - Measure 4-12 times anually - Twice annually (year 5)
48
In what other conditions are AFP elevated?
- Non-seminomatous germ cell tumour of ovary - hepatocellular carcinoma - Heptoblastoma (children) - Benign conditions: hepatitis, cirrhosis, biliary tract obstruction, alcoholic liver disease - Pregnancy as well
49
What are the AFP clinical applications?
- use in combination with hCG for non-seminomatous germ cell tumours - Independent prognostic marker of NSGCT - Diagnostic aid in hepatocellular carcinoma (HCC) and hepatoblastoma in patients with cirrhosis and focal lesions - AFP>200ug/L suggest HCC - AFP>400ug/L strong suggestive of HCC
50
What marker should be used instead of AFP for liver mets?
CEA
51
What is the marker of ovarian cancer? and when is it used?
CA125 - mainly used for monitoring treatment | - Also to distinguish between benign from malignant pelvic masses
52
What should CA125 be used in conjugtion with?
Transvaginal ultrasound for early detection in women with hereditary symptoms
53
What are the NICE guidelines for ovarian cancers in regards to CA125?
- Check CA125 if symptomatic of ovarian cancer - If Ca125>35kU/L refer to ultrasound - Symptoms are: abdominal bloating, early satiety, loss of appetite, IBS like symptoms
54
What are some key markers in breast cancers and what do they tell us?
- Oestrogen progesteron receptors measured to ID those that can be treated with endocrine therapy - HER2 receptor positive allow for herceptin treatment - BRCA1 and 2 mutations increase the risk
55
What is herceptins mechanism of treatment?
- It is a monoclonal antibody interfering with HER2 receptors - HER2 regulate growth, adhesion, migration and differentiation - Herceptin inhibits cell overproduction - Does improve late stage metstatic breast cancers
56
What is a classical tumour marker is used in breast cancer? how does the sensitivity change depedning on stage?
- CA15.3 increased in breast cancer with distant mets - sensitivity of up to 36% in early stages - sens 100% in advanced disease - Major use is in post-treatment monitoring
57
What other conditions are associated with raised CA15.3?
Raised in benign and malignant disease of lung, Gi and reproductive systems and also in liver disease
58
What is the tumour marker can be used in colorectal malignancy?
CEA - 70% of malignancies but do not appear in early stage - Most useful in post treatment monitoring and as an indicator of recurrance
59
What can cause false positives of colorectal malignancy?
Anything causing CEA release Other malignancy - Breast, lung, pancrease etc - Raised in benign conditions such as liver disease, obstructive jaundice, Crohns disease, pancreatitis, renal disease Smokers as well
60
What is the current colorectal cancer screenin in the UK?
National scheme using faecal occult blood | - All individuals >60 are screened
61
What is CA19.9 and how can it be used as a tumour marker?
Produced by primary malignancy in pancreatic cancer - Low sensitivity and specificity in early diagnosis - Used to monitor treatment This is a sialyated lewis antigen - patients lacking lewis antigen will not express CA19.9
62
What causes falsely elevated CA19.9?
- Colorectal, oesophageal and hepatocellular damage | - In bengign conditions: pancreatitis, cirrhosis and disease of bile ducts
63
What is the prostate cancer marker? is this specific enough?
Prostate cancer considered the only malignancy causing elevated PSA, but PSA is not specific to prostate - Elevated levels in benign prostate hypertrophy, UTI, urinary retention, acute and chronic prostatitis - Transient elevation following TURP, prostate biopsy, prostate massage, ejaculation
64
What are the main applicaitons to PSA?
- With DRE can aid in diagnosis - prognosis - surveillance following diagnosis - monitoring therapy
65
How can we distinguish between benign prostate hypertrophy and prostate cancer?
Total vs free PSA - Malignant prostate produce more bound PSA - low level of free in relation to total indicates cancer - high levels of free= normal prostate, BPH or prostatits
66
What is a noninvasive multianalyte test for cancer?
CancerSEEK - 8 cancer protiens and gene mutations from circulating blood - sensitivity 70% (30-98%)

Disease of Major Organs (14 decks)

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