Tumor Markers

Problem with immunoassays
High concentration of the analyte gives false negatives (exceed the binding antibody & the signal bearing antibody) - why we do dilutions

Low analytic sensitivity - lowest analyte concentration that will yield a result other than zero

can cause significant interference in any immunoassay - antibodies which have broad reactivity, cross species
Sandwich assays can give both falsse + & -

Normal <3, >20 ng/ml rare except malignancy

Colon -affected by tumor stage (higher with distant mets), grade (higher with well diffed), ploidy(higher with aneuploid), site (left >right), obstruction (inc with bowel obstruction), liver function(higher with dysfunction), higher preop CEA = worse outcome

Smoking, PUD, IBD, pancreatitis, hypothyroidism, biliary obstruction, cirrhosis

WD gastric adenoca, breast, lung, pancreas, Medullary thyroid, cervical adeno, urothelial
NOT ELEVATED IN ESOPH

fetal serum - from fetal liver & yolk sac, reaches adult levels @ 1 yr

usu no more than 100mg/dl
pregnancy, hepatitis, cirrhosis

usu>500, but can overlap lower
HCC, yolk sac, hepatoblastoma

L3 variant binds to Lens culinaris lectin

4-10 ng/ml
30-40% will have cancer

increases senstivity in young men, increases specifiicty in older men

PSA/volume of prostate
Works well for small prostates
>0.15 abnormal doesn't perform better than PSA

protease, mostly bound to proteins - antichymotropsin, alpha2macroglobin, alpha1 protein inhibiitor

rate of change in successive PSAs
>0.75 ng/ml/yr - abnormal

Low free PSA - more likely to have cancer
helps when PSA <10
cannot do after manipulation - wait weeks
process within 2 hrs or freeze

anomolous clipping truncated forms
increase in pro-PSA & truncated forms in prostate cancer
works if PSA btwn 2.5-4.0

3 consective increases in PSA
single rise to trigger hormone therapy

Should be undetectable -

MUC1 protein - breast cancer
30% low stage breast ca
70% advanced stage breast ca
CA 15-3 (25 U/mL) & 27.29 (100 u/ml)

benign ovarian cysts, b9 breast, b9 liver,
CA15-3, sarcoid, lupus, cirrhosis

ER/PR - + respond to hormonal therapy(estrogen deprivation, anti-estrogens(tamoxifen, aromatase inhibitors)

codes for epidermal growth factor - ErbB2 - gene amplification - overexpression - poor prognostic factor- Herceptin effective in treating, FISH, IHC,

Lewis a blood group Ag
80-90% pancreatic cancer (20lb wt loss, bili >3 & CA19-9 >37 = PPV for pancreatobiliary ca)
also esoph & instestines
>1000 diagnostic malignancy

<100 ng/ml
pancreatitis, cholestasis, cholangitis, cirrhosis

nonmucinous ovarian epithelial tumors
Not good screening - stage I less than 50% elevated CA 125
<35 U/ml is normal

>65 U/ml with pelvic mass - PPV >95% for malignancy
Fall during tx - tx efficacy
persistant elevated >35 U/ml predicts residual disease
Rising CA 125 suggests relapse

pregnancy, fibroids, b9 cysts, PID, ascites, endometriosis), endometrial ca, breast ca, fallopian tube ca, pancreas ca, colon ca

epidermal growth factor receptor - use in colon, lung, h&n, esophagus

tumor recurrence in follicular cancers
increase in anti-tgb antibodies suggests recurrence
all functional thyroid tissue is ablated
Can be affected by anti-tgb ab

Mucinous ovarian CA - 50% stage I & 100% stage IV
60% gastric infiltrating carcinomas
urothelial ca - 20% low-grade vs 80% high stage
70% in RCC
85-90% pancreatic adeno ca & pancreatitis

pregnancy, chorioca, trophoblastic disease
marijuana use - low levels
15% pure seminomas

elevated with increased cell turnover
solid tumors
heme
multiple myeloma
monitor renal transplant rejection
inflammatory states (RA, SLE, IBD)

highly non specific

osteoblastic activity (active paget's osteogenic sarcoma, bone mets)
sensitive liver fxn (hepatic mets)

Placental type alk phos

produce serotonin
tryptophan to 5-HTP by tryptophane hydoxylase
5-HTP to 5-HT by dopa-decarboxylase
5-HT to H-HIAA by renal tubular MAO

produce 5-HT, histamine, catecholamines, 5-HTP

distal duodenum, jejunum, ileum, appendix, right colon - only 5-HT - portal circulation - cleared by liver unless liver with mets or more distal - carcinoid syndrome

usu non secretory - hCG

can be wnl in 20-30% with carcinoid tumor esp. foregut & hindgut
Falsely elevated in tryptophan diet
Plt serotonin most accurate marker for carcinoid tumor

synapto, neuropeptide K, pancreatic polypeptide, chromogranin A

plasma calcitonin (>10ng/L); CEA
thyroglobulin negative

Hashimotos, c-cell hyperplasia, small cell lung, breast, CRF, & ZE syndrome

pheos - secrete norepi & epi
paragang - secrete epi
norepi to epi by PNMT
epi, norepi & VMA

imipriamine, reserpine, guanethidine, NTG, MAOI

free plasma metanephrine - long term catecholamine secretion

Urine VMA & HVA
HVA - byproduct dopa & dopamine
VMA - byproduct norepi & epi

low VMA:HVA ratio - poor prognosis
NSE. LDH, ferritin

NMP 22 (NuMA - monitoring of pts with bladder cancer) -
BTA - complement factor H & CFH-rp in urine -

high incidence of aneuploidy in TCC - 3, 7, 17 & 9

PCA3 gene, DD3 - mRNA,