Armelle Vinceneux1,2, Franck Bruyère3, Olivier Haillot3, Thomas Charles4, Alexandre de la Taille5, Laurent Salomon5, Yves Allory6, Idir Ouzaid7, Laurence Choudat8, Morgan Rouprêt9, Eva Comperat10, Nadine Houede11, Jean-Baptiste Beauval12, Patrick Vourc'h13, Gaëlle Fromont1,2. 1. Department of Pathology, CHU de tours, Université François Rabelais, Tours, France. 2. INSERM UMR 1069, Tours, France. 3. Department of Urology, CHU de Tours, Pres Centre Val de Loire, Université François Rabelais de Tours, Tours, France. 4. Service d'Urologie, CHU de Poitiers, Université de Poitiers, Poitiers, France. 5. Department of Urology, Henri Mondor Hospital, AP-HP, Créteil, France. 6. Department of Pathology and Tissue Biobank Unit, Henri Mondor Hospital, AP-HP, Créteil, France. 7. Department of Urology, Bichat-Claude Bernard Hospital, AP-HP, Paris, France. 8. Department of Pathology, Bichat-Claude Bernard Hospital, AP-HP, Paris, France. 9. Department of Urology, Pitié- Salpétrière Hospital, Assistance Publique Hôpitaux de Paris, University Pierre et Marie Curie, Paris 6, Paris, France. 10. Department of Pathology, Pitié-Salpétrière Hospital, Assistance Publique Hôpitaux de Paris, University Pierre et Marie Curie, Paris 6, Paris, France. 11. Department of Medical Oncology, Groupe Hospitalier Universitaire Caremeau, Nîmes, France. 12. Department of Urology, Andrology and Renal Transplantation, CHU Rangueil, Toulouse, France. 13. Laboratoire de Biochimie et Biologie moléculaire, CHRU de Tours, INSERM U930, Université François-Rabelais, Tours, France.
Abstract
BACKGROUND: Ductal adenocarcinoma (DAC) is a rare and aggressive subtype of prostate cancer (PCa). In the present study, we analyzed the clinical and biological characteristics of DAC, in comparison with high grade conventional acinar PCa. METHODS: Samples and data were retrospectively collected from seven institutions and centrally reviewed. Immunohistochemistry was performed on tissue microarrays to assess the expression of candidate proteins, based on the molecular classification of PCa, including ERG, PTEN, and SPINK1. SPOP mutations were investigated from tumor DNA by Sanger sequencing. Relationships with outcome were analyzed using log-rank analysis and multivariable Cox regression. RESULTS: Among 56 reviewed prostatectomy specimens, 45 cases of DAC were finally confirmed. The pathological stage was pT3 in more than 66% of cases. ERG was expressed in 42% of DAC, SPINK1 in 9% (all ERG-negative), and two cases (ERG-negative) harbored a SPOP mutation. Compared to high grade conventional PCa matched for the pathological stage, cell proliferation was higher (P = 0.04) in DAC, and complete PTEN loss more frequent (P = 0.023). In multivariate analysis, SPINK1 overexpression (P = 0.017) and loss of PSA immunostaining (P = 0.02) were significantly associated with biochemical recurrence. CONCLUSION: these results suggest that, despite biological differences that highlighted DAC aggressiveness, the molecular classification recently proposed in conventional PCa could also be applied in DAC.
BACKGROUND:Ductal adenocarcinoma (DAC) is a rare and aggressive subtype of prostate cancer (PCa). In the present study, we analyzed the clinical and biological characteristics of DAC, in comparison with high grade conventional acinar PCa. METHODS: Samples and data were retrospectively collected from seven institutions and centrally reviewed. Immunohistochemistry was performed on tissue microarrays to assess the expression of candidate proteins, based on the molecular classification of PCa, including ERG, PTEN, and SPINK1. SPOP mutations were investigated from tumor DNA by Sanger sequencing. Relationships with outcome were analyzed using log-rank analysis and multivariable Cox regression. RESULTS: Among 56 reviewed prostatectomy specimens, 45 cases of DAC were finally confirmed. The pathological stage was pT3 in more than 66% of cases. ERG was expressed in 42% of DAC, SPINK1 in 9% (all ERG-negative), and two cases (ERG-negative) harbored a SPOP mutation. Compared to high grade conventional PCa matched for the pathological stage, cell proliferation was higher (P = 0.04) in DAC, and complete PTEN loss more frequent (P = 0.023). In multivariate analysis, SPINK1 overexpression (P = 0.017) and loss of PSA immunostaining (P = 0.02) were significantly associated with biochemical recurrence. CONCLUSION: these results suggest that, despite biological differences that highlighted DAC aggressiveness, the molecular classification recently proposed in conventional PCa could also be applied in DAC.
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