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24 Cards in this Set

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What are the strategies against cancer?
Prevention
- Smoking, abestos
- ? vaccines (e.g. HPV vaccine - cervical CA)

Screening program
- PAP smear
- Mammograms

Treatment
- surgery
- radiotherapy/chemotherapy
- hormones
- ? gene therapy
Ware we winning the battle against cancer?
Incidence of cancer in males and females has increased.

Mortabilty has decreased in males and females.
What is the most common cancer in Australia?
Colorectal cancer most common(2001)
What is the cancer with the highest death rate in Australia?
Pancreatic cancer (2001)
What can a tumour be indicated by?
Signs and Symptoms
- decreased weight, anorexia, mass

General Biochem
- LFTs (cholestatic) Increased Ca2+

Hormones
- ADH, ACTH, PTHrP, hCG

Tissue markers
- PSA, thyroglobulin

Strange protiens
- paraproteins, AFP, CEA, CA125, CA 19-9, CA 15-3

Cell surface marker
- beta2-microglobulin

Enzymes - LD

DNA - BRCA 1 & 2 for breast CA, ras oncogene for colon CA
Why do we measure tumour markers?
1. Detection early, treatable CA
2. Confirmation diagnosis
3. Staging (classification)
4. Monitoring - response to treatment, recurrence

1,2,3 - limited use
4 - IMPORTANT use
What are features of an ideal tumour marker?
- High sensitivity - detect early, treatable cancers
- High specificity - no false positive results
- Reflect tumour activity and mass - help guide treatment
- Prevents premature death from cancer

Tumour marker levels correlate reasonably well with tumour volume.

Lack of sufficient sensitivity and specificity limits its use in cancer screening.
What are some tumour marker problems?
1. Tumours do not always produce markers
2. Sensitivity - poor
- Negative result in people with cancer e.g. CEA only pikes 5% Dukes A colon CA, not for screeening fo cancer
3. Specificity - poor
- positive result in people without cancer e.g. PSA in prostatitis, CA 19-9 in cholestasis
4. False +ve/-ve result due to assay problems
What are some assay problems?
1. HIGH DOESE HOOK EFFECT - falsely low values
2. HETEROPHILE ANTIBODY INTERFERENCE - falsely high values e.g.heterophile antibody (human antimouse antibody)
3. Values from different labs are not interchangeable
What is PSA?
Prostate specific antigen
- A glycoprotein (serine protease) secreted by prostatic epithelial cells. Confined to the gland but "leak" into the circulation
- In teh glood, mostly bound to proteins: e.g. alpha-antichymotrypsin
- PSA is tissue specific but not tumour specific
- commonly used reference range - <mg/mL

PRIMARY TUMOUR - Prostate
BENIGN CONDITIONS - Prostatitis (8 weeks), BPH, prostatic trauma, after ejaculation (2d)
DIAGNOSIS - yes
MONITORING TREATMENT - very helpful
FOLLOW-UP AFTER TREATMENT
- 6 monthly x 5y then annually
- any detectable PSA after radical proctectomy indicates recurrence
SCREENING GENERAL POPULATION - controversial
- not recommended in australia
What is the ideal for PSA as a tumour marker? What is teh reality for PSA with BPH?
Ideal - Cut off at 4ng/mL

Reality - false positives, false negatives, grey area
What are problems with PSA?
- PSA is neither sensitive or specific (PPV 20-30% at PSA >4ng/mL)
- Follow up procedure invasive
- Treatment has significant complications
- Many people with prostate CA die of other causes
- Despite increase incidence due to introduction of PSA, mortality has not changed - ? Are we detecting clinically less important cases?
What are ways to increase PSA specificity?
1. Clinical indication - lower threshold for +ve family Hx or abnormal DRE
2. Use age-adjusted reference ranges for different ethnic groups
3. Free PSA/total PSA ratio (fPSA)
4. PSA velocity - >0.75ug/L/year --> high risk for CA
5. PSA density - Against volume of prostate by ultrasound: ug/L/mL
What are some onco-foetal proteins?
Carcinoembryonic Antigen (CEA)
Alpha foetal protein (AFP)
Beta human chorionic gonadotrophin (beta-hCG)
What is CEA?
Onco-foetal protein made by normal and malignant epithelial tissues.

PRIMARY TUMOUR - colorectal CA
OTHER TUMOURS - breast, lung, GI epithelium, heat & neck
BENIGN CONDITIONS - usually <20ng/mL; cigarette smoking, most GI conditions, hypothyroidism
FOLLOW-UP AFTER Rx - 2-3 monthy, at least 2y
What are AFP?
Alpha foetoprotein

- Foetal albumin made by yolk sack and liver
- high in infants and ruing pregnancy
- adults <10ug/mL
- half life ~ 5 days

PRIMARY TUMOURS - hepatoma, germ cell CA (non-seminomatous)
AFP and hepatoma
- hepatoma is commonly a complication of chronic hepatitis (esp. Hep C)
- AFP > 1000ug/L usually indicate hepatoma
- Current debates on its use in hepatoma screening
- Problems:
> small incrases can be due to early hepatoma or liver deases
> increase in benign conditions (usually <200ug/L): hepatitis, cirrhosis
AFP and germ cell tumours
- AFP and beta-hCG are important in the treatment of testicular nonseminomatous germ cell tumour
- levels failure to fall after surgery indicate residual disease
- follow up:
> at least 6 repeats in 1st year post op
> then quaterly x 1 year
> less frequent thereafter
Describe Beta-hCG as a tumour marker
Normally produced by placenta - increased in pregnancy

PRIMARY TUMOUR - nonseminomatous germ cell tumour, gestational trophoblastic disease
OTHER TUMOURS - rarely, GI cancers
BENIGN CONDITIONS - hypogonadal state, marijuana use
FOLLOW-UPAFTER Rx
- For seminomatous germ cell tumour - same as AFP
- For gestational trophoblastic disease - Monthly x 1 year
What are some carbohydrate antigens?
CA 15-3
CA 19-9
CA 125
CA 15-3
- a monoclonal antibody developed to detect glycoprotein found on breast cell epithelium
- same levels in male and females
- no change in pregnancy and lactation

PRIMARY TUMOUR - breast
OTHER TUMOURS - colon, lung, pancreas
BENIGN CONDITIONS - benign breast, liver and kidney disorders, pancreatitis, biliary dis, cirrhosis
MONITORING TREATMENT AND RECURRENCE - helpful
FOLLOW-UP AFTER Rx - 4-6 monthly for recurrence
CA 19-9
An intracellular adhesion molecule made by pancreatic and biliary cells

PRIMARY TUMOUR - Pancreatic CA, biliary tract CA
OTHER TUMOURS - colon, esophageal and hepatic CA
BENIGN CONDITIONS - usually <1000ng/mL, pancreatitis, biliary dis, cirrhosis
MONITORING TREATMENT AND RECURRENCE: Helpful
FOLLOW-UP AFTER Rx - 2-3 monthly, at least 2 yr
CA 125
A monoclonal antibody developed to detect glycoprotein found on ovarian epithelial tumour cells

PRIMARY TUMOUR - ovarian CA
OTHER TUMOURS - endometrial, fallopian, breast, lung, GI
BENIGN CONDITIONS - menstruation, pregnancy, fibroids, ovarian cysts, endometriosis, pelvic inflammation, cirrhosis, ascites, and pleural & pericardial effusions
FOLLOW-UP AFTER Rx - 3 monthly, at least 2 years
SUMMARY OF TUMOUR MARKERS
Tumour markers can provide valuable assistance in management of patients with known malignancy if used appropriately
- Have limited role for cancer screening
> thye do not have sufficient sensitivity or specificity
> low prevalence of the disease in general population
> +ve reulst are far more likely to be false +ve than true +ve
- Tests can be also falsely +ve or -ve due to assay problems - talk to the lab if doubt
- need to monitor levels by the same laboratory