Tumor Markers Flashcards

1
Q

The Hook effect

A
  • a very high concentration of an analyte gives a falsely low result
  • high concentration exceeds the binding capacity of both the binding capture antibodies and the signal bearing antibodies preventing their association
  • if the sample is sufficiently diluted the assay will give an appropriate result
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2
Q

Effect of heterophile antibodies on immunoassays

A

Can cause false positives or false negatives

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3
Q

PSA

A
  • Annual PSA measurement + digital rectal exam is recommended for men > 50 yo
  • Abnormal DRE or PSA > 4 ng/mL is indication for prostate bx
  • Recommendation now controversial
  • PSA is organ specific but not cancer specific
  • May be elevated in
    • benign prostatic hyperplasia
    • prostatitis
    • prostatic infarct
    • following needle biopsy
  • Only 30-40% of men with elevated PSA have prostate cancer
  • There is intraindividual variation and variation according to race, with levels being higher in blacks
  • Poor sensitivity; many men with prostate cancer have serum PSA < 4 ng/mL
  • Adjunctive PSA indices
    • Age specific cutoffs (PSA increases with age)
    • PSA density (PSA divided by estimated prostatic volume)
    • PSA velocity (rate of change in successive PSA determinations)
    • free PSA (lower free PSA fraction correlates with the prostate cancer)
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4
Q

Colorectal cancer screening

  • testing methods
  • false positive results from
  • false negative results from
A
  • Recommended screening
    • fecal occult blood testing
      • guaiac based testing: hemoglobin has endogenous peroxidase activity that can oxidize guaiac in the presence of H2O2 to a blue color
      • false positive can result from
        • NSAIDs
        • consumption of heme (in meat)
        • consumption of peroxidase (turnips and horseradish)
      • false negatives result from excess vitamin C consumption
      • immmunohistochemical testing: no dietary restrictions
    • flexible sigmoidoscopy
    • barium enema
    • colonoscopy
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5
Q

CEA

A
  • Increased in some patients with colon cancer
  • not recommended for colon cancer screening
  • plays a role in preoperative evaluation of patients with known colon cancer and in the postoperative monitoring of such patients
  • highpreoperative CEA concentration implies a worse overall outcome
  • CEA is elevated in
    • 25% of tumors confined to the colon
    • 50% with nodal metastasis
    • 75% with distant metastases
  • CEA may be increased in
    • gastric adenocarcinoma
    • breast cancer
    • lung cancer
    • pancreatic adenocarcinoma
    • medullary thyroid carcinoma
    • cervical adenocarcinoma
    • urothelial carcinoma
  • Mild CEA elevation can be caused by
    • smoking
    • peptic ulcer disease
    • inflammatory bowel disease
    • pancreatitis
    • hypothyroidism
    • biliary obstruction
    • cirrhosis
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6
Q

Thyroglobulin

A
  • detection of tumor recurrence in differentiated (follicular and papillary) thyroid carcinoma
  • antithyroglobulin antibodies are potential sources of interference
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7
Q

Cancer antigen (CA) 125

A
  • elevated in nonmucinous epithelial ovarian neoplasms
  • may be elevated in
    • pregnancy
    • leiomyomas
    • benign ovarian cysts
    • pelvic inflammation
    • ascites
    • endometriosis
    • endometrial, Fallopian tube, pancreas, breast, and colon neoplasms
  • levels tend to decrease in postmenopausal women
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8
Q

CA 27.29 and CA 15-3

A
  • CA27.29 (also called BR 27.29) and CA15-3 measure different epitopes of a single antigen-the protein product of the breast cancer associated MUC1 gene
  • Both are elevated in 60-70% of women with advanced stage breast cancer
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9
Q

CA 19-9

A
  • Marker for pancreatic adenocarcinoma; elevated in 80% at presentation
  • May be elevated in patients with other malignancies
    • hepatobiliary
    • gastric
    • colorectal
    • breast
  • May be elevated in
    • pancreatitis
    • cholestasis
    • cholangitis
    • cirrhosis
  • Not produced by Lewis negative patients
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10
Q

AFP

  • normally synthesized where?
  • elevations in benign states
  • marker for what tumors
A
  • Normally synthesized in the yolk sac, fetal liver, and fetal GI tract
  • Elevated in normal pregnancy, cirrhosis, and hepatitis
  • Elevated in yolk sac tumors and most HCC
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11
Q

HCG elevated in

A
  • pregnancy
  • trophoblastic disease
  • choriocarcinoma
  • 15% of pure seminomas
  • rare tumors from other sites (GI tract, GU tract)
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12
Q

Beta2 microglobulin

A
  • elevated whenever there is increased cell death
  • an independent prognostic factor in multiple myeloma
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13
Q

Alkaline phosphatase as a tumor marker

A
  • An indication of osteoblastic activity
  • Elevated in osteogenic sarcoma or bone mets
  • Sensitive test for hepatic mets
  • Regan isoenzyme may be elevated in a variety of advanced malignancies
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14
Q

Markers of carcinoid tumors

A
  • Produce serotonin (5 hydroxytryptamine, 5-HT) that is metabolized and excreted in urine as 5 hydroxyindoleacetic acid (5-HIAA)
  • Foregut carcinoids produce
    • histamine
    • catecholamines
    • 5-hydroxytryptophan (5-HTP)
  • Midgut carcinoids usually make only seratonin
  • Hindgut carcinoids are often nonsecretory
  • Other peptides that can be produced in excess
    • synaptophysin
    • neuropeptide K
    • pancreatic polypeptide (PP)
    • chromogranin A (CGA)
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15
Q

Markers of medullary thyroid carcinoma

A
  • plasma calcitonin with or without provocative testing with calcium infusion
  • serum CEA commonly elevated
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16
Q

Paraganglioma and pheochromocytoma markers

A
  • Produce NE with or without epinephrine; some are nonsecretory
    • NE is metabolized to normetanephrine, which is metabolized to vanillylmandelic acid (VMA)
    • Epinephrine is metabolized to metanephrine, which is metabolized to vanillylmandelic acid (VMA)
  • Lab tests
    • urinary VMA
    • urinary metanephrines
    • urinary catecholamines
    • plasma metanephrines
    • plasma catecholamines
  • Medications that interfere with the above assays
    • imipramine
    • reserpine
    • guanethidine
    • nitroglycerin
    • monamine oxidase inhibitors
17
Q

Neuroblastoma markers

A
  • Urine VMA and homovanillic acid (HVA) are elevated in most cases
  • HVA is the final metabolic product of DOPA and dopamine
  • VMA is the final product of norepinephrine and epinephrine
  • Nonspecific markers used to follow disease activity
    • NSE
    • LDH
    • ferritin
18
Q

Urine markers for urothelial carcinoma

A
  • NMP 22 (nuclear matrix protein 22) test detects a nuclear matrix protein called NuMA (nuclear mitotic apparatus) that is released from the nuclei of tumor cells when they die
  • Bladder tumor antigen (BTA) test detects complement factor H and complement factor H related proteins (CFH-rp) in the urine