Clinicopathological Comparison Between <i>GREB1</i>- and <i>ESR1</i>-Rearranged Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Systematic Review
Livia Maccio,
Damiano Arciuolo,
Angela Santoro,
Antonio Raffone,
Diego Raimondo,
Susanna Ronchi,
Nicoletta D’Alessandris,
Giulia Scaglione,
Michele Valente,
Belen Padial Urtueta,
Francesca Addante,
Nadine Narducci,
Emma Bragantini,
Jvan Casarin,
Giuseppe Angelico,
Stefano La Rosa,
Gian Franco Zannoni,
Antonio Travaglino
Affiliations
Livia Maccio
Surgical Pathology Unit, S. Chiara Hospital, 38122 Trient, Italy
Damiano Arciuolo
Unità Operativa Complessa Anatomia Patologica Generale, Dipartimento di Scienze Della Salute Della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Angela Santoro
Unità Operativa Complessa Anatomia Patologica Generale, Dipartimento di Scienze Della Salute Della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Antonio Raffone
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40127 Bologna, Italy
Diego Raimondo
Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
Susanna Ronchi
Pathology Unit, Department of Oncology, ASST Sette Laghi, 21100 Varese, Italy
Nicoletta D’Alessandris
Unità Operativa Complessa Anatomia Patologica Generale, Dipartimento di Scienze Della Salute Della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Giulia Scaglione
Unità Operativa Complessa Anatomia Patologica Generale, Dipartimento di Scienze Della Salute Della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Michele Valente
Unità Operativa Complessa Anatomia Patologica Generale, Dipartimento di Scienze Della Salute Della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Belen Padial Urtueta
Unità Operativa Complessa Anatomia Patologica Generale, Dipartimento di Scienze Della Salute Della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Francesca Addante
Unità Operativa Complessa Anatomia Patologica Generale, Dipartimento di Scienze Della Salute Della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Nadine Narducci
Unità Operativa Complessa Anatomia Patologica Generale, Dipartimento di Scienze Della Salute Della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Emma Bragantini
Surgical Pathology Unit, S. Chiara Hospital, 38122 Trient, Italy
Jvan Casarin
Department of Medicine and Technological Innovation, University of Insubria, 21100 Varese, Italy
Giuseppe Angelico
Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy
Stefano La Rosa
Pathology Unit, Department of Oncology, ASST Sette Laghi, 21100 Varese, Italy
Gian Franco Zannoni
Unità Operativa Complessa Anatomia Patologica Generale, Dipartimento di Scienze Della Salute Della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Antonio Travaglino
Pathology Unit, Department of Oncology, ASST Sette Laghi, 21100 Varese, Italy
Introduction: Among uterine tumors resembling ovarian sex cord tumors (UTROSCTs), it has been suggested that GREB1-rearranged cases are biologically distinct from ESR1-rearranged cases and might be considered as a separate entity. Objectives: The aim of this systematic review was to assess the difference between GREB1- and ESR1-rearranged UTROSCTs with regard to several clinico-pathological parameters. Methods: Three electronic databases were searched from their inception to February 2025 for all studies assessing the presence of GREB1 and ESR1 rearrangements in UTROSCTs. Exclusion criteria comprised overlapping patient data, case reports, and reviews. Statistical analysis was performed to compare clinicopathological variables between GREB1- and ESR1-rearranged UTROSCTs. Dichotomous variables were compared by using Fisher’s exact test; continuous variables were compared by using Student’s t-test. A p-value Results: Six studies with 88 molecularly classified UTROSCTs were included. A total of 36 cases were GREB1-rearranged, and 52 cases were ESR1-rearranged. GREB1-rearranged UTROSCTs showed a significantly older age (p p = 0.002), less common submucosal/polypoid growth (p = 0.005), higher mitotic index (p = 0.010), more common LVSI (p = 0.049), and higher likelihood to undergo hysterectomy (p = 0.008) compared to ESR1-rearranged cases. No significant differences were detected with regard to margins, cytological atypia, necrosis, retiform pattern, and rhabdoid cells. No significant differences were found in the immunohistochemical expression of any of the assessed markers (wide-spectrum cytokeratins, α-inhibin, calretinin, WT1, CD10, CD56, CD99, smooth muscle actin, desmin, h-caldesmon, Melan-A/MART1, SF1, or Ki67). GREB1-rearranged UTROSCTs showed significantly lower disease-free survival compared to ESR1-rearranged UTROSTCs (p = 0.049). Conclusions: In conclusion, GREB1-rearranged UTROSCTs occur at an older age, are less likely to display a submucosal/polypoid growth, and exhibit larger size, a higher mitotic index, more common lymphovascular space invasion, and lower disease-free survival compared to ESR1-rearranged UTROSCTs. Nonetheless, the similar immunophenotype suggests that they belong to the same tumor family. Further studies are necessary to confirm this point.
