Clinical Chemistry

low free PSA fraction or elevated bound PSA fraction

PSAfree:PSAtotal <10%

correlates with?

Prostate cancer

PSA=protease–>minimize the viscosity of the ejaculate

Prostatic manipulation and instrumentation –> effect

– PSAtotal

– PSAfree

– minimal

– markedly=> measure before/several weeks after manipulation

Specimen handling

PSAfree

processed within 2hrs / freeze

–>less stable than bound PSA

When % PSAfree measurement–>advantage?
prostate volume < 60cc

PSAtotal = 2.5 – 4.0

?test can improve prostate Ca diagnosis

increased pro-PSA and truncated PSA isoforms1

1pPSA–>anomalous clipping

Correlation between PSA and tm reccurence

weak in first 5yrs post treatment

preop–> PSA ~ tumor volume and stage

 

Nonneoplastic coditions a/w elevated CEA1

Smoking, peptic ulcer dz,IBD,pancreatitis, hypothyroidism, biliary/bowel obstruction, cirrhosis

1CEA < 10ng/mL

CEA elevations in malignancies other than colon
Gastric(well diff, intest. type), breast, lung,pancreas,cervical,urothelial, MTC

Colorectal Ca and degree of CEA elevation

Affected by?

Tumor stage, grade, site (L>R), ploidy

obstruction,liver function (metabolism)

post-treatment surveillance of colorectal Ca

serial CEA measurements

most sensitive–> liver mets

poorly sensitive–> locoregional recurrence

Thyroglobulinserum – Cause of

1. Underestimation

2. Overestimation

Anti-thyroglobulin Ab’s-;10% (nml Indiv.),;20%Pt w thyroid Ca

2. Macro-thyroglobulin

;

Pt w PTC/FTC and;anti-thyroglobulin Ab’s

Tumor marker?

Serial quantitative [anti-thyroglobulin Ab]serum

increase<–Ag stimulation<– recurrence

Marker for mucinous ovarian Ca, Urothelial Ca & RCC

Tumor-Associated Trypsin Inhibitor (TATI)

also in pancreatic adenoca–>limited specificity (pancreatitis)

gastric ca (60%) –> diffuse, infiltrative,signet ring

TATI expression and tumor prognosis
Adverse prognostic factor
Nonneoplastic cause of TATI elevation

Renal failure

Pancreatitis–> degree of elevation ~ severity

CA 125

Major role in monitoring of which Pt

Non-mucinous epithelial ovarian neoplasm

elevated only ~ 50% –> stage I dz

elevated CA 125

Nonneoplastic causes

Pregnancy,fibroids, benign ovarian cysts, pelvic inflammation, ascites, endometriosis

elevated CA 125

In which nonovarian neoplasms?

Fallopian tube, endometrium, pancreas,breast, colon

post-menopausal woman w palpable adnexal mass & CA 125> 65 U/mL

Dx?

Ovarian malignancy ( epithelial, non-mucinous)

PPV >95%

Serum markers for breast Ca

CA27.29 (more sensitive &specific), CA15-3

–> different epitopes of a single Ag = protein product of breast ca assoc MUC1 gene

elevated CA27.29/15-3

nonneoplastic causes?

benign ovarian cysts, liver dz, benign breast dz

CA 15-3–> sarcoidosis and lupus

elevated CA27.29

non-breast malignancies

Colon, stomach, pancreas, prostate, lung
Best prognostic markers in breast cancer

IHC: ER, PR, Her-21 (c-erb-2) Nc staining % of tm cells

–> correlates well with biochemical assays (ligand binding)

1IHC & / FISH –>Rx: trastuzumab

Her-2 assesment in breast cancer

IHC:Only membranous staining–>only Inv. component

0-3+ –> 2+ => FISH

Best marker for pancreticobiliary adenoca and assesment to treatment response

CA19-9 >10001 U/L

1not seen in benign dz ( <100 U/L)

CA 19-9

What type of Ag

 = Lewis blood group Ag

not produced by Lepeople

AFP – physiologic effect

Site of synthesis?

Major component of fetal serum –> ~ albumin

Yolk sac, fetal liver/GI tract

undetectable–>post partum, adults < 5.4ng/mL

benign conditions < 100 ng/mL

AFP and malignancy

Yolk sac tm–> [AFP] ~ prognosis

HCC –>[AFP] ~ overlap w benign dz

Hepatoid variant of gastric Ca

low level elevation of hCG in non-pregnant woman
Marijuana use
Marker for monitoring transplant rejection

beta2-Micoglobulin –> surface-most nucleated cells

–>non-covalent link to MHC I

Increased cell turnover1 => elevated beta2M2

1solid tm & hematolymphoid neoplasms,2renal isufficiency

Raised Alkaline Phosphatase

Causes

–>osteoblastic activity (osteogenic sarcoma, bone mets,

active Paget disease of bone)

~ Liver function–> hepatic mets (carcioids~prognosis)

Pt with gonadal/urologic cancer and elevated placental-type alkaline phosphatase
Regan isoenzyme of Alk Phos

modest quantity of 5-HT(serotonin), histamine, catecholamines &5-HTP

Dx: Tumor? Location?

Carcinoid

Foregut: stomach, proximal duodenum and lung

 

Only serotonin production in high quantities

Dx: Tumor? Location?

Carcinoid

Midgut: distal duodenum,jejunum,ileum,appendix,right colon

Carcinoid tumor

non secretory for indoles

Location?

 

Distal 1/3 of transverse, descending colon,sigmoid colon and rectum

~hCG

Most accurate marker for detection of carcinoid tm

Platelet serotonin

–> take up serotonin from the serum @ constant rate

–> not affected by diet (tryptophan rich)

Urine test

 elevated 5-HIAA

DDx:

Carcinoid –> 20-30% ~ normal (foregut,hindgut)

False elevation–> tryptophan rich diet

5-HT–> platelets –>some 5-HT–> renal tubules => 5-HIAA

Plasma marker in neuroendocrine tm

–> Tm burden and treatment response

Chromogranin A

Small cell NE, pheo,carcinoid,islet cell tm

 

Increased [Calcitonin]plasma

DDx?

MTC

Hashimoto, C-cell hyperplasia, breast ca

20 –>chronic renal failure, Zollinger-Ellison syndrome

[Calcitonin]plasma < 10ng/L

more sensitive test?

provocative testing – pentagastrin/omeprazole/Ca++

–> in MEN II families

MTC

Marker of worse prognosis

high CEA => greater de-differentiation

Tumor with secretion of:

Epinephrine & norepinephrine

Dx?

Pheochromocytoma–> adrenal medulla –> norepinephrine –PNMT–>epinephrine

Extra-adrenal tm –> mainly norepinephrine

Urinary VMA

DDx?

Paraganglioma1/Pheochromocytoma2/ Neuroblastoma3

–> fractionation of catecholamines/metanephrines

1norepinephrine–> normetanephrine –> VMA

2epinephrine–> metanephrine –> VMA

3also homovanillic acid–> metabolic product of DOPA & dopamine

Most accurate test for initial screening of

tumors of chromaffin cells

1.free Metanephrineplasma

2. Metanephrine/Catecholamineurine

plasma catecholamines –> poor sensitivity –> episodic release

plasma metanephrines–> long term catecholamine secretion

free Metanephrineplasma Metanephrine/Catecholamineurine

–> equivocal results –> ?test to clarify tests?

Clonidine suppression test
low VMA:HVA and prognosis

<– poorly difeerentiated Neuroblastoma

=> worse prognosis

Monitoring of patients w known hx/o urothelial Ca

Marker? DDx of + results

urinary NMP22–> sensitive,nonspecific (1-6wks post Sx)

Inflammation–>rapid cell turnover –> false +

Leukocytes–> false +

Bladder tumor antigen

false +

Stone disease, inflammation, BPH
Urine test for Prostatic adenoCa

PCA3/DD3

RNA fro urine sediment–> quantitative real time PCR

=> # DD3 RNA transcripts (nontranslated mRNA)

elevated [PSA]serum 1 in prostatic adenoca

Cause?

1Increase leakage into the extracellular matrix

KLK3 gene (encodes PSA) –> not upregulated in Prostate adenoca 

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