S Garnier1, J Vendrell2, B Boillot3, G Karsenty4, A Faure5, T Blanc6, L Soustelle7, V Phe8, A Even9, E Chartier-Kastler10, P Ravasse11, G Poinas12, B Leizour7, P Costa7, L Galmiche12, F Iborra11, O Bouali13, X Game14, J Solassol2, N Kalfa1,15,16. 1. Service de Chirurgie et Urologie Pédiatrique, CHU Montpellier, Montpellier, France. 2. IRCM, INSERM 1194, Université de Montpellier, Laboratoire de Biologie des Tumeurs Solides, CHU Montpellier, Montpellier, France. 3. Service d'Urologie, CHU de Grenoble, Grenoble, France. 4. Service d'Urologie et de Transplantation Rénale, CHU Hôpital la Conception, APHM, Marseille, France. 5. Service de Chirurgie Pédiatrique, CHU Hôpital Timone, APHM, Marseille, France. 6. Service de Chirurgie Pédiatrique, Hôpital Necker-Enfants-Malades, APHP, Paris, France. 7. Service d'Urologie, CHU de Nîmes, Nîmes, France. 8. Service d'Urologie, Hôpital Universitaire La Pitié Salpêtrière, Paris, France. 9. Service de Médecine Physique et Réadaptation, Hôpital Raymond-Poincaré, Garches, France. 10. Service de Chirurgie Pédiatrique, CHU de Caen, Caen, France. 11. Service d'Urologie et de Transplantation Rénale, CHU Montpellier, Marseille, France. 12. Département d'anatomopathologie, Hôpital Necker-Enfants-Malades, APHP, et Université Sorbonne, Paris, France. 13. Service de Chirurgie Pédiatrique, Hôpital des Enfants de Toulouse, Toulouse, France. 14. Service d'Urologie, CHU de Toulouse, Toulouse, France. 15. National Reference Network DSD DevGen, Centre Constitutif Sud, CHU Montpellier, Montpellier, France. 16. Université de Montpellier, Montpellier, France.
Abstract
PURPOSE: We report the natural history and prognosis of tumors after augmentation enterocystoplasty, with a molecular analysis using an oncogene panel to search for potential targeted therapies. MATERIALS AND METHODS: This multicenter, nationwide, retrospective study included 16 patients. A panel of 21 clinically relevant oncogenes was tested on archival tumor specimens using next-generation sequencing. Survival rate was the main clinical outcome and sequences were compared to the reference genome for the genetic outcome. RESULTS: Augmentation enterocystoplasties were performed mainly for congenital neurogenic bladder and bladder exstrophy at a median patient age of 17 years (range 4 months to 45 years). Most of the malignancies were diagnosed because of clinical manifestations, with a median latency period of 20 years. Adenocarcinomas were mainly found after gastrocystoplasty, whereas urothelial cell carcinomas were typically found after colocystoplasty. Of the 16 patients 13 were diagnosed at an advanced stage of the disease (positive lymph nodes in 7, distant metastases in 6). The overall 1-year survival rate was 56%. Only 3 patients remained disease-free at a median followup of 70 months. Of the 9 tumors with analyzable DNA 4 were wild-type and 5 harbored missense mutations (KIT-p.Pro573Ser, PDGFRA-p.Glu587Lys, KRAS-p.Gly12Asp, ERBB4p.Arg484Lys, CTNNB1-p.Ser37Phe and p.Ser47Asn). CONCLUSIONS: Malignancy after augmentation enterocystoplasty is diagnosed late with frequent metastases and a very low 1-year survival rate. More than half the tested samples harbored missense mutations in oncogenes accessible to targeted therapies. An international collaboration to enlarge the genetic panel analysis of these tumors may offer new therapeutic hope to patients.
PURPOSE: We report the natural history and prognosis of tumors after augmentation enterocystoplasty, with a molecular analysis using an oncogene panel to search for potential targeted therapies. MATERIALS AND METHODS: This multicenter, nationwide, retrospective study included 16 patients. A panel of 21 clinically relevant oncogenes was tested on archival tumor specimens using next-generation sequencing. Survival rate was the main clinical outcome and sequences were compared to the reference genome for the genetic outcome. RESULTS: Augmentation enterocystoplasties were performed mainly for congenital neurogenic bladder and bladder exstrophy at a median patient age of 17 years (range 4 months to 45 years). Most of the malignancies were diagnosed because of clinical manifestations, with a median latency period of 20 years. Adenocarcinomas were mainly found after gastrocystoplasty, whereas urothelial cell carcinomas were typically found after colocystoplasty. Of the 16 patients 13 were diagnosed at an advanced stage of the disease (positive lymph nodes in 7, distant metastases in 6). The overall 1-year survival rate was 56%. Only 3 patients remained disease-free at a median followup of 70 months. Of the 9 tumors with analyzable DNA 4 were wild-type and 5 harbored missense mutations (KIT-p.Pro573Ser, PDGFRA-p.Glu587Lys, KRAS-p.Gly12Asp, ERBB4p.Arg484Lys, CTNNB1-p.Ser37Phe and p.Ser47Asn). CONCLUSIONS: Malignancy after augmentation enterocystoplasty is diagnosed late with frequent metastases and a very low 1-year survival rate. More than half the tested samples harbored missense mutations in oncogenes accessible to targeted therapies. An international collaboration to enlarge the genetic panel analysis of these tumors may offer new therapeutic hope to patients.
Authors: Chelsea Cornell; Francesca Khani; Adeboye O Osunkoya; Andres Matoso; Hiroshi Miyamoto; Jennifer B Gordetsky; Safia N Salaria; Giovanna A Giannico Journal: Hum Pathol Date: 2021-11-19 Impact factor: 3.466
Authors: Jennifer Hinley; Rosalind Duke; Jessica Jinks; Jens Stahlschmidt; David Keene; Raimondo M Cervellione; Imran Mushtaq; Paolo De Coppi; Massimo Garriboli; Jennifer Southgate Journal: Am J Pathol Date: 2022-03-28 Impact factor: 5.770