Dr Kayode S AdedapoPrincipal Investigator

• 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.

One of such prostate cancer biomarker is α-methylacyl-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 β-oxidation of branched-chain fatty acids (Ferdinandusse et al, 2000; Kotti et al, Schmitz et al, 1995).[1-3]

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.

• 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.

• 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.

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. 

• 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.  

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.

 

• 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

Categories of Assay Kit

AMOUNT

IGF – 1 ELISA Kit IGF – 3 ELISA Kit Immunohistochemistr

y Kit) Kit For AMACR

Autoantibodies Needle and Syringe Sample Bottles Total

180,000 190,000 270,000

230,000

6000 6000 882,000

Professor Olayiwola ShittuDepartment of Surgery, COM., UI.

Dr. C. A. OkoloDepartment of Pathology, COM., UI

PhD Research student, Mr. Clement Famurewa

Dr Adura AdedapoDepartment of Pharmacology and Therapeutics, COM, UI.

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.

 

Parkin DM, Whelan SL, Ferlay J, et al. Cancer Incidence of five continents vol. 7, Lyons, France: IARC; 1997.

  Osegbe DN. Prostate Cancer in Nigerians:

Facts and Non-facts. J. Urol. 1997; 157 : 1340 – 1343.