Markers of Field Cancerization: Proposed Clinical Applications in Prostate Biopsies

Table 1

Molecular markers that are in accordance with the definition of prostate field cancerization reported in the literature¹.

Type of molecular alteration^2	Specific molecular marker	Reference^3
Cytomorphological changes	Nuclear chromatin structure	[34]
	Nuclear chromatin structure	[35]
	Nuclear texture	[36]
Epigenetic changes	Methylation of GSTp1 and RARβ2	[37]^4
	Methylation of GSTp1, RARβ2, and APC	[38]
	Methylation of RASSF1A	[39]
	Methylation of RARβ2, APC, and RASSF1A	[40]
	Methylation of HIN-1	[41]
Genomic DNA changes	Profile of infrared spectroscopy	[42]
	Profile of infrared spectroscopy	[43]
	Profile of infrared spectroscopy	[44]
	Telomere attrition	[45]
	Telomere attrition	[46]
	TMPRSS2-ERG fusion	[47]
	Content of DNA	[32]
	Telomere attrition	[48]
	Telomere attrition	[49]
	Telomere attrition	[50]^4
Mitochondrial DNA changes	Mutation	[51]
	Deletion	[52]
	Deletion	[53]
Gene expression changes	Gene expression signature (671 genes)	[54]
	cDNA microarrays (12,625 probes)	[55]
	Noncoding RNA from PCA3 gene	[56]
	Panel of 8 genes	[57]
	Gene fusion transcript of TMPRSS2-ERG	[58]
	cDNA microarrays (37,123 probes)	[59]
	PSCA	[60]
Protein expression changes	PS2	[61]
	Androgen receptor	[62]^4
	COX-2	[63]
	Androgen receptor	[64]^4
	Phosphorylated Akt-1	[65]
	EPCA	[66]
	EPCA	[67]
	Calcium channel P2X7	[33]
	AMACR	[68]
	Ki67 and MCM-2	[69]
	Activated Akt	[70]
	EPCA	[71]
	AMACR	[72]
	β-catenin	[73]
	Androgen receptor	[74]^4
	Expression of Akt	[75]
	PDGFRβ	[76]^4
	Phosporylated EGFR	[77]
	EGR-1 and IGF1R	[78]
	UDP-glucose dehydrogenase	[79]
	Prostate tumor overexpressed 1	[80]
	EGR-1 and FAS	[81]
NMR spectra	Metabolites	[82]

¹Combined and updated from Nonn et al., 2009 [5] and Halin et al., 2011 [4].
²Additional markers of field cancerization that are not strictly molecular in nature, but rather represent cellular changes or adaptations to the presence of the tumor are cell morphological architecture [83], increased numbers of mast cells and macrophages [84–86], and enhanced microvessel density [87, 88].
³Within a type of molecular alteration group, the studies are reported in chronological order; references are original articles only; additional review articles are listed in the text.
⁴Reported in stromal cells.