Transcript ALPHA – METHYLACYL –CoA RACEMASE: A MORE SENSITIVE

Dr Kayode S Adedapo
Principal Investigator
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Currently, prostate-specific antigen (PSA) is
the most commonly used serum biomarker
for the screening and diagnosis of prostate
cancer
However, PSA is not a cancer-specific
marker, it has poor specificity.
Consequently, there is great need for
additional serum biomakers to supplement or
replace PSA for the detection of prostate
cancer in patients.
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One of such prostate cancer biomarker is αmethylacyl-CoA racemase (AMACR),
an enzyme that catalyses the racemization of
R-stereoisomers of branched-chain fatty
acids to S-stereoisomers
plays an important role in peroxisomal βoxidation of branched-chain fatty acids
(Ferdinandusse et al, 2000; Kotti et al,
Schmitz et al, 1995).[1-3]
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AMACR has been shown to be elevated in
prostate cancer by several recent studies.
Chandan et al, 2004[4] have presented
evidence that AMACR activity is consistently
elevated in prostate cancer tissue specimens
relative to benign epithelia.
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Alpha-methylacyl-CoA racemase (AMACR) has
been shown, by recent studies, to be over
expressed in prostate cancer epithelia;
Studies on prostate tissue specimens have
demonstrated that AMACR protein is a highly
specific and sensitive marker for prostate cancer.
It is therefore necessary to investigate further,
especially in this part of the world, the
expression of AMACR in prostate cancer patients
as a prospective molecular biomarker for the
disease.
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Prostate cancer is becoming an increasingly
important public health problem among adult
men in most western communities.
Nigeria, which was formerly regarded as a
low-incidence area is no longer left out
(Ukoli et al, 2003; Ogunbiyi and Shittu, 1999;
Parkin et al, 1997; Osegbe, 1997) Asserted a
steep rise in the occurrence of the disease.
Many notable Nigerians have lost their lives
to this dreaded disease.
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To test whether α-methylacyl CoA racemase
(AMACR) is a sensitive and specific maker for
prostate cancer.
To test whether high level of IGF-1 is a risk
factor to prostate cancer.
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To determine the expression level of AMACR by
immunohistochemical techniques in Nigerian
patients with prostate cancer and benign
prostatic hyperplasia as controls.
To determine immune response to AMACR in
plasma of the patients and controls using ELISA
method.
To determine the sensitivity and specificity of
AMACR immunodetection of prostate
adenocarcinomas in comparison to total
prostate-specific antigen.
To determine the IGF-1 and IGFBP-3 in plasma of
the patient and controls using ELISA method.
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Alpha-methylacyl CoA racemase (AMACR) is a
biochemical marker of prostate cancer with
high sensitivity and specificity.
High insulin-like growth factor-1 ( IGF-1)
level is a risk factor for prostate cancer.
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Is there any significant difference in the expression of
AMACR in prostate cancer tissue and BPH tissue?
Is there any significant difference in the plasma levels
of immune response to AMACR in prostate cancer
samples and that of BPH?
Is the IGF-1 levels in patients with prostate cancer
samples significantly different from that of BPH?
What is the type of association between IGF-1 and
IGFBP-3?
Any other correlation between IGF-1 and other
selected variable risk factors?
10 mls blood from histology proven subjects
with prostate cancer and Benign prostate
hyperplasia:
 For Humoral respose to AMACR
 IGF-1
 IGFBP-3
Immnuhistochemistry for AMACR
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IGF – 1 ELISA Kit
Categories of Assay Kit
IGF – 3 ELISA Kit
Immunohistochemistry
Kit)
Kit For AMACR
Autoantibodies
Needle and Syringe
Sample Bottles
Total
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180,000
190,000
270,000
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230,000
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6000
6000
882,000
AMOUNT
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Professor Olayiwola Shittu
Department of Surgery, COM., UI.
Dr. C. A. Okolo
Department of Pathology, COM., UI
PhD Research student, Mr. Clement Famurewa
Dr Adura Adedapo
Department of Pharmacology and
Therapeutics, COM, UI.
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Ferdinandusse S, Denis S, Lodewijk I, Dacremont G, Waterham
HR, Wanders RJ. Subcellcular localization and physiological
role of alpha-methylacyl – CoA racemase. J. Lipid Res. 2000;
41: 1890-6.
Kotti TJ, Savolainen K, Helander HM, Yagi A, Novikov DK,
Kalkkinen N, et al. In
mouse alpha – methylacyl – CoA
racemase, the gene product is simultaneously located in
mitochondria and peroxisomes. J. Biol Chem 2000;
275:20887 – 95.
Ukoli F, Osime V, Akereyeni F, Okunzuwa O, Kittles R,
Adanis-Campebell L. Prevalences of elevated serum prostate
specific antigen in rural Nigeria. Int. J. Urology 2003; 10(6):
315 – 322.
Ogunbiyi JO, Shittu OB. Increased incidence of prostate cancer
in Nigerians. J. Natl. Med. Assoc. 1999; 91:159-164.
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Parkin DM, Whelan SL, Ferlay J, et al. Cancer
Incidence of five continents vol. 7, Lyons,
France: IARC; 1997.
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Osegbe DN. Prostate Cancer in Nigerians:
Facts and Non-facts. J. Urol. 1997; 157 :
1340 – 1343.