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. 2017 Sep;19(9):707-715.
doi: 10.1016/j.neo.2017.06.003. Epub 2017 Aug 19.

Up-regulation of Biglycan is Associated with Poor Prognosis and PTEN Deletion in Patients with Prostate Cancer

Frank Jacobsen  1 , Juliane Kraft  1 , Cornelia Schroeder  2 , Claudia Hube-Magg  1 , Martina Kluth  1 , Dagmar S Lang  1 , Ronald Simon  3 , Guido Sauter  1 , Jakob R Izbicki  2 , Till S Clauditz  1 , Andreas M Luebke  1 , Andrea Hinsch  1 , Waldemar Wilczak  1 , Corinna Wittmer  1 , Franziska Büscheck  1 , Doris Höflmayer  1 , Sarah Minner  1 , Maria Christina Tsourlakis  1 , Hartwig Huland  4 , Markus Graefen  4 , Lars Budäus  4 , Imke Thederan  4 , Georg Salomon  4 , Thorsten Schlomm  5 , Nathaniel Melling  2
Affiliations

Up-regulation of Biglycan is Associated with Poor Prognosis and PTEN Deletion in Patients with Prostate Cancer

Frank Jacobsen et al. Neoplasia. 2017 Sep.

Abstract

Biglycan (BGN), a proteoglycan of the extracellular matrix, is included in mRNA signatures for prostate cancer aggressiveness. To understand the impact of BGN on prognosis and its relationship to molecularly defined subsets, we analyzed BGN expression by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Seventy-eight percent of 11,050 interpretable cancers showed BGN expression, which was considered as low intensity in 47.7% and as high intensity in 31.1% of cancers. BGN protein expression rose with increasing pathological tumor stage, Gleason grade, lymph node metastasis and early PSA recurrence (P<.0001 each). Comparison with our molecular database attached to the TMA revealed that BGN expression was linked to presence of TMPRRS2:ERG fusion and PTEN deletion (P<.0001 each). In addition, BGN was strongly linked to androgen-receptor (AR) levels (P<.0001), suggesting a hormone-depending regulation of BGN. BGN up-regulation is a frequent feature of prostate cancer that parallels tumor progression and may be useful to estimate tumor aggressiveness particularly if combined with other molecular markers.

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Figures

Figure 1
Figure 1
Representative pictures of BGN staining in prostate cancer with negative (A), low (B), and high-intensity (C) staining at 100×, insets 400× magnification and spot size of 600 μm.
Figure 2
Figure 2
Association between BGN staining, ERG status determined by immunohistochemistry and PTEN deletion by fluorescence in situ hybridization.
Figure 3
Figure 3
Association between positive BGN staining and 10q23 (PTEN), 5q21 (CHD1), 6q15 (MAP3K7), 3p13 (FOXP1) deletions in all cancers (A), in ERG-negative (B), and ERG-positive cancers (C).
Figure 4
Figure 4
Association between BGN staining results and androgen receptor (AR) in all cancers, ERG-negative tumors, and ERG-positive tumors.
Figure 5
Figure 5
Kaplan–Meier plots of prostate specific antigen (PSA) recurrence after radical prostatectomy and pathological tumor stage (A), classical Gleason score (B), quantitative Gleason score (C), BGN expression in all cancers (D), in PTEN deletion (E), and PTEN normal subset (F).
See this image and copyright information in PMC

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