Prostate field cancerization denotes molecular alterations in histologically normal tissues adjacent to
tumors. Such alterations include deregulated
protein expression, as we have previously shown for the key
transcription factor early growth response 1 (EGR-1) and the lipogenic
enzyme fatty acid synthase (FAS). Here we add the two secreted factors
macrophage inhibitory cytokine 1 (MIC-1) and
platelet derived growth factor A (
PDGF-A) to the growing list of
protein markers of prostate field cancerization. Expression of MIC-1 and
PDGF-A was measured quantitatively by immunofluorescence and comprehensively analyzed using two methods of signal capture and several groupings of data generated in human cancerous (n = 25), histologically normal adjacent (n = 22), and disease-free (n = 6) prostate tissues. A total of 208 digitized images were analyzed. MIC-1 and
PDGF-A expression in
tumor tissues were elevated 7.1x to 23.4x and 1.7x to 3.7x compared to disease-free tissues, respectively (p<0.0001 to p = 0.08 and p<0.01 to p = 0.23, respectively). In support of field cancerization, MIC-1 and
PDGF-A expression in adjacent tissues were elevated 7.4x to 38.4x and 1.4x to 2.7x, respectively (p<0.0001 to p<0.05 and p<0.05 to p = 0.51, respectively). Also, MIC-1 and
PDGF-A expression were similar in
tumor and adjacent tissues (0.3x to 1.0x; p<0.001 to p = 0.98 for MIC-1; 0.9x to 2.6x; p<0.01 to p = 1.00 for
PDGF-A). All analyses indicated a high level of inter- and intra-tissue heterogeneity across all types of tissues (mean coefficient of variation of 86.0%). Our data shows that MIC-1 and
PDGF-A expression is elevated in both prostate
tumors and structurally intact adjacent tissues when compared to disease-free specimens, defining field cancerization. These secreted factors could promote
tumorigenesis in histologically normal tissues and lead to
tumor multifocality. Among several clinical applications, they could also be exploited as indicators of disease in false negative biopsies, identify areas of repeat biopsy, and add molecular information to
surgical margins.