Antonio Travaglino1, Antonio Raffone2,3, Diego Raimondo4, Annarita Gencarelli1, Italia Esposito5, Cinzia Gallo6, Francesco Paolo Improda5, Salvatore Giovanni Vitale7, Antonio Mollo8, Paolo Casadio4, Renato Seracchioli4, Fulvio Zullo5, Luigi Insabato1. 1. Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy. 2. Division of Gynaecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC), IRCCS Azienda Ospedaliero-Univeristaria Di Bologna. S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138, Bologna, Italy. anton.raffone@gmail.com. 3. Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Via Sergio Pansini, 5, 80131, NaplesNaples, Italy. anton.raffone@gmail.com. 4. Division of Gynaecology and Human Reproduction Physiopathology, Department of Medical and Surgical Sciences (DIMEC), IRCCS Azienda Ospedaliero-Univeristaria Di Bologna. S. Orsola Hospital, University of Bologna, Via Massarenti 13, 40138, Bologna, Italy. 5. Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Via Sergio Pansini, 5, 80131, NaplesNaples, Italy. 6. Gynecology and Obstetrics Unit, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy. 7. Obstetrics and Gynecology Unit, Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy. 8. Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, 84081, Baronissi, Italy.
Abstract
BACKGROUND: Uterine leiomyosarcoma (uLMS) may show loss of expression of B-cell lymphoma-2 (Bcl-2) protein. It has been suggested that Bcl-2 loss may both be a diagnostic marker and an unfavorable prognostic marker in uLMS. OBJECTIVE: To define the diagnostic and prognostic value of Bcl-2 loss in uLMS through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to May 2020 for all studies assessing the diagnostic and prognostic value of Bcl-2 loss of immunohistochemical expression in uLMS. Data were extracted to calculate odds ratio (OR) for the association of Bcl-2 with uLMS vs leiomyoma variants and smooth-muscle tumors of uncertain malignant potential (STUMP), and hazard ratio (HR) for overall survival; a p value < 0.05 was considered significant. RESULTS: Eight studies with 388 patients were included. Loss of Bcl-2 expression in uLMS was not significantly associated with a diagnosis of uLMS vs leiomyoma variants and STUMP (OR = 2.981; p = 0.48). Bcl-2 loss was significantly associated with shorter overall survival in uLMS (HR = 3.722; p = 0.006). High statistical heterogeneity was observed in both analyses. CONCLUSION: Loss of Bcl-2 expression appears as a significant prognostic but not diagnostic marker in uLMS. The high heterogeneity observed highlights the need for further research and larger studies.
BACKGROUND: Uterine leiomyosarcoma (uLMS) may show loss of expression of B-cell lymphoma-2 (Bcl-2) protein. It has been suggested that Bcl-2 loss may both be a diagnostic marker and an unfavorable prognostic marker in uLMS. OBJECTIVE: To define the diagnostic and prognostic value of Bcl-2 loss in uLMS through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to May 2020 for all studies assessing the diagnostic and prognostic value of Bcl-2 loss of immunohistochemical expression in uLMS. Data were extracted to calculate odds ratio (OR) for the association of Bcl-2 with uLMS vs leiomyoma variants and smooth-muscle tumors of uncertain malignant potential (STUMP), and hazard ratio (HR) for overall survival; a p value < 0.05 was considered significant. RESULTS: Eight studies with 388 patients were included. Loss of Bcl-2 expression in uLMS was not significantly associated with a diagnosis of uLMS vs leiomyoma variants and STUMP (OR = 2.981; p = 0.48). Bcl-2 loss was significantly associated with shorter overall survival in uLMS (HR = 3.722; p = 0.006). High statistical heterogeneity was observed in both analyses. CONCLUSION: Loss of Bcl-2 expression appears as a significant prognostic but not diagnostic marker in uLMS. The high heterogeneity observed highlights the need for further research and larger studies.