Review Article

Cellular Plasticity in Prostate Cancer Bone Metastasis

Table 3

Details of studies analysing expression of EMT/MET markers in PC bone metastases.

StudyMarkerNo. of BM specimensComparison tissue (No. of specimens)ResultsSignificance for differential expression

Bryden et al., 1999 [45] E-Cadherin20Different grades of BM tissues Decrease in expression with increasing tumour gradeNR

Bryden et al., 2002 [46]E-Cadherin, β-catenin14Matched primary PC (14)mRNA for both markers was expressed uniformly in 9/14 primary PC. In BM, 6/14 showed negative mRNA for one or both markers and 6/14 expressed both heterogeneously NR

Lang et al., 2002 [47]Vimentin8Primary (54)16/54 of primary expressed vimentin with ≤50% staining cells. 7/8 BM expressed vimentin with 100% of cells staining positive in 5 specimens NR

Chen et al., 2004 [48]Wnt-1/β-catenin23 (from 9 patients)Primary PC (62, from 49 patients)
LN (23, from 9 patients)
High Wnt-1/β-catenin in 85% of BM and 77% of LN. Highest expression was observed in BM for BM (& for LN) versus normal tissues

Saha et al., 2008 [49]E-Cadherin, β-catenin17Primary PC (22)
BPH (11)
BM tissues showed higher frequency of homogenous expression of both markers compared to primary PC for BM versus primary PC

Saha et al., 2008 [50] E-Cadherin15Primary PC (20)
BPH (11)
Higher expression of unmethylated gene and homogenous protein in BM compared to primary tissues for BM versus primary PC

Pontes et al., 2010 [51]E-Cadherin, β-catenin28Matched primary PC (6)For E-cadherin & β-catenin, respectively, there was abnormal expression in 86% and 82% of 28 BM specimens. In matched specimens, normal expression was seen in 5/6 and 3/6 of primary PC and abnormal expression was seen in 5/6 of BM for both markersNR

Armstrong et al., 2011 [52]Vimentin, CK2CTCs (10, 2 matched)Coexpression of vimentin and CK in 10/10 of CTCs Absent vimentin expression in 2/2 of CK-positive BM. Strong vimentin expression in bone stromaNR

Putzke et al., 2011 [53] E-Cadherin109LN (30)
Liver (18)
Other (8)
Higher expression in BM compared to all soft tissue metastases for BM versus all soft tissue metastases

Sethi et al., 2011 [54] E-Cadherin, Vimentin, PDGF-D, NF-kB, Notch-1, ZEB110Primary PC (10)Higher expression of Notch-1 in BM compared to primary PC. No quantitative difference in expression for other markers. In primary and BM, EMT markers (vimentin & NF-kB) had higher expression at invasive tumour front than within tumour centre. The opposite pattern was observed for E-cadherin For BM versus primary PC: for E-cadherin, vimentin, PDGF-D, NF-kB, for Notch-1, NR for ZEB1

Wan et al., 2012 [55]β-catenin27Association with AR expression in BM tissuesNuclear localization of β-catenin in 10/27 BM specimens. Localization was inversely associated with AR expression for inverse association between nuclear localization of β-catenin and AR expression

AR: androgen receptor, BM: bone metastasis, BPH: benign prostatic hyperplasia, CK: cytokeratin, CTCs circulating tumour cells, ISH: in situ hybridisation, LN: lymph node, MS-PCR: methylation specific polymerase chain reaction, No.: number, and NR: not reported.