{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:33:15Z","timestamp":1791275595538,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,8,14]],"date-time":"2008-08-14T00:00:00Z","timestamp":1218672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies have revealed the potential involvement of Hedgehog (Hh) signalling in proliferation and invasive behaviour of prostate carcinoma (PCa). The aim of this study was to specify the role of Sonic Hh (Shh), Desert Hh (Dhh) and Indian Hh (Ihh) in the natural history of PCa. Hh ligands expression was compared in primary hormone\u2010naive PCa (HNPC), hormone\u2010treated PCa (HTPC) and hormone\u2010refractory PCa (HRPC), using immunohistochemistry. Shh and Dhh were expressed by both epithelial and stromal cells of prostate tissues. Ihh was only expressed by stromal cells. For the three ligands, mRNA and immunostaining were not correlated. In HNPC, Shh epithelial expression was significantly associated with high Gleason scores (<jats:italic>p<\/jats:italic> = 0.03), metastatic lymph nodes (<jats:italic>p<\/jats:italic> = 0.004) and Dhh epithelial staining was associated with high pT stages (<jats:italic>p<\/jats:italic> = 0.003), seminal vesicle invasion (<jats:italic>p<\/jats:italic> = 0.03) and bladder neck invasion (<jats:italic>p<\/jats:italic> = 0.0008). Negative Shh staining in stromal cells was associated with high Gleason scores (<jats:italic>p<\/jats:italic> = 0.015), high pT stages (<jats:italic>p<\/jats:italic> = 0.01) and bladder neck invasion (<jats:italic>p<\/jats:italic> = 0.04). Concomitant absence of Shh and Dhh expression in stromal cells was an independent prognostic parameter for biological recurrence on multivariate analysis (<jats:italic>p<\/jats:italic> = 0.01). Epithelial expression of Shh and Dhh was increased in HTPC compared to HNPC (<jats:italic>p<\/jats:italic> = 0.02 and <jats:italic>p<\/jats:italic> = 0.04). Interestingly, <jats:italic>in vitro<\/jats:italic>, transcript analysis also showed increased expression of these 2 Hh ligands when androgen\u2010sensitive LNCaP cells were maintained in androgen\u2010free medium mimicking hormonal therapy. Epithelial expression of Dhh was increased (<jats:italic>p<\/jats:italic> &lt; 0.0001) in HRPC compared to HNPC, while stromal expression of Shh and Dhh was decreased (<jats:italic>p<\/jats:italic> &lt; 0.0001). In conclusion, the Hh signalling pathway is associated with pejorative pathological parameters in HNPC and is up\u2010regulated in epithelial cells of HTPC and HRPC. Moreover, the lack of Hh molecules in stromal cells seems to be associated with invasive and hormone\u2010refractory behaviours and suggests specific changes in stromal\u2013epithelial crosstalks during PCa progression. Copyright \u00a9 2008 Pathological Society of Great Britain and Ireland. 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