Abstract
OBJECTIVES
AND DESIGN:
We
identified a novel TRIM59 gene, as an early signal transducer in two (SV40Tag
and Ras) oncogene pathways in murine prostate cancer (CaP) models. We explore
its clinical applications as a multitumour marker detecting early tumorigenesis
by immunohistochemistry (IHC).
SETTING
AND PARTICIPANTS:
88 CaP
patients were from a tissue microarray (TMA) of radical prostatectomy specimen,
42 patients from a 35 multiple tumour TMA, 75 patients with renal cell
carcinoma (RCC) and 92 patients from eight different tumour groups (breast,
lung, parotid, gastrointestinal, female genital tract, bladder, kidney and
prostate cancer).
RESULTS:
TRIM59
upregulation specifically in tumour area was determined by IHC in 291 cases of
37 tumour types. To demonstrate that TRIM59 upregulation is 'tumour-specific',
we characterised a significant correlation of TRIM59 IHC signals with
tumorigenesis and progression, while in control and normal area, TRIM59 IHC
signal was all negative or significantly low. TRIM59 protein upregulation in
prostate and kidney cancers was detectable in both intensity and extent in
early tumorigenesis of prostate intraepithelial neoplasia (p<0.05) and grade
1 of RCC (p<0.05), and stopped until high grades cancer. The results of the
correlation in these two large cohorts of tumour types confirmed and repeated
murine CaP model studies. Enhanced TRIM59 expression was identified in most of
the 37 different tumours, while the highest intensities were in lung, breast,
liver, skin, tongue and mouth (squamous cell cancer) and endometrial cancers.
Multiple tumour upregulation was further confirmed by comparing relative scores
of TRIM59 IHC signals in eight tumours with a larger patient population; and by
a mouse whole-mount embryo (14.5 days post conception) test on the origin of
TRIM59 upregulation in epithelial cells.
CONCLUSIONS:
TRIM59
may be used a novel multiple tumour marker for immunohistochemical detecting
early tumorigenesis and could direct a novel strategy for molecular-targeted
diagnosis and therapy of cancer.
Source:
TRIM59, a novel multiple cancer biomarker for immunohistochemical
detection of tumorigenesis. Khatamianfar V, Valiyeva F,
Rennie PS, Lu WY, Yang BB, Bauman GS, Moussa M, Xuan JW (jim.xuan@lhsc.on.ca).
BMJ Open. 2012 Oct 8;2(5).
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