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

Abstract

AIMS:

Malignant 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.

METHODS:

As 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.

RESULTS:

The 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.

CONCLUSIONS:

Increased 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.

• Authors: Amarnath Challapalli, Sebastian Trousil, Steve Hazell, Kasia Kozlowski, Mihir Gudi, Eric O Aboagye, Stephen Mangar
• Journal: Journal of clinical pathology (J Clin Pathol) Vol. 68 Issue 9 Pg. 703-9 (Sep 2015) ISSN: 1472-4146 [Electronic] England
• PMID: 26041862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Biomarkers, Tumor
• CHKA protein, human
• Choline Kinase

Topics

• Biomarkers, Tumor (analysis)
• Blotting, Western
• Choline Kinase (analysis, biosynthesis)
• Disease-Free Survival
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Prognosis
• Prostatic Neoplasms (enzymology, mortality)
• Reverse Transcriptase Polymerase Chain Reaction