Exploiting altered patterns of choline kinase-alpha expression on human prostate tissue to prognosticate prostate cancer

Author:

Challapalli Amarnath,Trousil Sebastian,Hazell Steve,Kozlowski Kasia,Gudi Mihir,Aboagye Eric O,Mangar Stephen

Abstract

AimsMalignant transformation results in overexpression of choline-kinase (CHK) and altered choline metabolism, which is potentially detectable by immunohistochemistry (IHC). We investigated the utility of CHK-alpha (CHKA) IHC as a complement to current diagnostic investigation of prostate cancer by analysing expression patterns in normal (no evidence of malignancy) and malignant human prostate tissue samples.MethodsAs an initial validation, paraffin-embedded prostatectomy specimen blocks with both normal and malignant prostate tissue were analysed for CHKA protein and mRNA expression by western blot and quantitative reverse transcriptase PCR (qRT-PCR), respectively. Subsequently, 100 paraffin-embedded malignant prostate tumour and 25 normal prostate cores were stained for both Ki67 (labelling-index: LI) and CHKA expression.ResultsThe validity of CHKA-antibody was verified using CHKA-transfected cells and siRNA knockdown. Immunoblotting of tissues showed good resolution of CHKA protein in malignant prostate, verifying use of the antibody for IHC. There was minimal qRT-PCR detectable CHKA mRNA in normal tissue, and conversely high expression in malignant prostate tissues. IHC of normal prostate cores showed mild (intensity) CHKA expression in only 28% (7/25) of samples with no Ki67 expression. In contrast, CHKA was expressed in all malignant prostate cores along with characteristically low proliferation (median 2% Ki67-LI; range 1–17%). Stratification of survival according to CHK intensity showed a trend towards lower progression-free survival with CHK score of 3.ConclusionsIncreased expression of CHKA, detectable by IHC, is seen in malignant lesions. This relatively simple cost-effective technique (IHC) could complement current diagnostic procedures for prostate cancer and, therefore, warrants further investigation.

Publisher

BMJ

Subject

General Medicine,Pathology and Forensic Medicine

Reference35 articles.

1. THE COMBINATION OF PREOPERATIVE PROSTATE SPECIFIC ANTIGEN AND POSTOPERATIVE PATHOLOGICAL FINDINGS TO PREDICT PROSTATE SPECIFIC ANTIGEN OUTCOME IN CLINICALLY LOCALIZED PROSTATE CANCER

2. Treatment strategies for high-risk locally advanced prostate cancer

3. Cuvilier O , Malavaud B . Biomarkers of aggressiveness in prostate cancer. InTech, 2011.

4. Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells;Ackerstaff;Cancer Res,2001

5. Phospholipid metabolism in cancer cells monitored by 31P NMR spectroscopy;Daly;J Biol Chem,1987

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