Histological staining of reactive stroma has been shown to be a predictor of biochemical recurrence in
prostate cancer, however, molecular markers of the stromal response to
prostate cancer have not yet been fully delineated. The objective of this study was to determine whether or not the stromal
biomarkers detected with a
thioredoxin-targeted nanodevice could be used to distinguish the stroma associated with
benign prostatic hyperplasia from that associated with PCA. In this regard, we recently demonstrated that a
thioredoxin-targeted nanodevice selectively binds to reactive stroma in frozen prostate
tumor tissue sections. To accomplish this, random frozen prostate tissue sections from each of 35 patients who underwent resection were incubated with the nanodevice and graded for fluorescent intensity. An adjacent section from each case was stained with
Hematoxylin &
Eosin to confirm the diagnosis. Select cases were stained with Masson's Trichrome or immunohistochemically using
antibodies to
thioredoxin reductase 1,
thioredoxin reductase 2 or
peroxiredoxin 1. Our results demonstrate that the graded intensity of nanodevice binding to the stroma associated with PCA was significantly higher (pā=ā0.0127) than that of
benign prostatic hyperplasia using the t-test. Immunohistochemical staining of adjacent sections in representative cases showed that none of the two commonly studied
thioredoxin interacting
protein partners mirrored the fluorescence pattern seen with the nanodevice. However,
thioredoxin reductase 2 protein was clearly shown to be a
biomarker of
prostate cancer-associated reactive stroma whose presence distinguishes the stroma associated with
benign prostatic hyperplasia from that associated with
prostate cancer. We conclude that the signal detected by the nanodevice, in contrast to individual targets detected with
antibodies used in this study, originates from multiple
thioredoxin interacting
protein partners that distinguish the M2 neutrophil and macrophage associated inflammatory response in
prostate cancer-associated stroma from the CD4+ T-Lymphocyte linked
inflammation in
benign prostatic hyperplasia.