Clinicopathological Comparison Between <i>GREB1</i>- and <i>ESR1</i>-Rearranged Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Systematic Review

<b>Introduction:</b> Among uterine tumors resembling ovarian sex cord tumors (UTROSCTs), it has been suggested that <i>GREB1</i>-rearranged cases are biologically distinct from <i>ESR1</i>-rearranged cases and might be considered as a separate entity. <b>Obj...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/15/6/792
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author 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
author_facet 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
author_sort Livia Maccio
collection DOAJ
description <b>Introduction:</b> Among uterine tumors resembling ovarian sex cord tumors (UTROSCTs), it has been suggested that <i>GREB1</i>-rearranged cases are biologically distinct from <i>ESR1</i>-rearranged cases and might be considered as a separate entity. <b>Objectives:</b> The aim of this systematic review was to assess the difference between <i>GREB1</i>- and <i>ESR1</i>-rearranged UTROSCTs with regard to several clinico-pathological parameters. <b>Methods:</b> Three electronic databases were searched from their inception to February 2025 for all studies assessing the presence of <i>GREB1</i> and <i>ESR1</i> rearrangements in UTROSCTs. Exclusion criteria comprised overlapping patient data, case reports, and reviews. Statistical analysis was performed to compare clinicopathological variables between <i>GREB1</i>- and <i>ESR1</i>-rearranged UTROSCTs. Dichotomous variables were compared by using Fisher’s exact test; continuous variables were compared by using Student’s <i>t</i>-test. A <i>p</i>-value < 0.05 was considered significant. <b>Results:</b> Six studies with 88 molecularly classified UTROSCTs were included. A total of 36 cases were <i>GREB1</i>-rearranged, and 52 cases were <i>ESR1</i>-rearranged. <i>GREB1</i>-rearranged UTROSCTs showed a significantly older age (<i>p</i> < 0.001), larger tumor size (<i>p</i> = 0.002), less common submucosal/polypoid growth (<i>p</i> = 0.005), higher mitotic index (<i>p</i> = 0.010), more common LVSI (<i>p</i> = 0.049), and higher likelihood to undergo hysterectomy (<i>p</i> = 0.008) compared to <i>ESR1</i>-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). <i>GREB1</i>-rearranged UTROSCTs showed significantly lower disease-free survival compared to <i>ESR1</i>-rearranged UTROSTCs (<i>p</i> = 0.049). <b>Conclusions:</b> In conclusion, <i>GREB1</i>-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 <i>ESR1</i>-rearranged UTROSCTs. Nonetheless, the similar immunophenotype suggests that they belong to the same tumor family. Further studies are necessary to confirm this point.
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spelling doaj-art-b29feec39f944d199051510a76d710d92025-08-20T02:11:09ZengMDPI AGDiagnostics2075-44182025-03-0115679210.3390/diagnostics15060792Clinicopathological Comparison Between <i>GREB1</i>- and <i>ESR1</i>-Rearranged Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Systematic ReviewLivia Maccio0Damiano Arciuolo1Angela Santoro2Antonio Raffone3Diego Raimondo4Susanna Ronchi5Nicoletta D’Alessandris6Giulia Scaglione7Michele Valente8Belen Padial Urtueta9Francesca Addante10Nadine Narducci11Emma Bragantini12Jvan Casarin13Giuseppe Angelico14Stefano La Rosa15Gian Franco Zannoni16Antonio Travaglino17Surgical Pathology Unit, S. Chiara Hospital, 38122 Trient, ItalyUnità 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, ItalyUnità 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, ItalyDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, 40127 Bologna, ItalyDivision of Gynecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyPathology Unit, Department of Oncology, ASST Sette Laghi, 21100 Varese, ItalyUnità 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, ItalyUnità 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, ItalyUnità 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, ItalyUnità 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, ItalyUnità 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, ItalyUnità 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, ItalySurgical Pathology Unit, S. Chiara Hospital, 38122 Trient, ItalyDepartment of Medicine and Technological Innovation, University of Insubria, 21100 Varese, ItalyDepartment of Medicine and Surgery, Kore University of Enna, 94100 Enna, ItalyPathology Unit, Department of Oncology, ASST Sette Laghi, 21100 Varese, ItalyUnità 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, ItalyPathology Unit, Department of Oncology, ASST Sette Laghi, 21100 Varese, Italy<b>Introduction:</b> Among uterine tumors resembling ovarian sex cord tumors (UTROSCTs), it has been suggested that <i>GREB1</i>-rearranged cases are biologically distinct from <i>ESR1</i>-rearranged cases and might be considered as a separate entity. <b>Objectives:</b> The aim of this systematic review was to assess the difference between <i>GREB1</i>- and <i>ESR1</i>-rearranged UTROSCTs with regard to several clinico-pathological parameters. <b>Methods:</b> Three electronic databases were searched from their inception to February 2025 for all studies assessing the presence of <i>GREB1</i> and <i>ESR1</i> rearrangements in UTROSCTs. Exclusion criteria comprised overlapping patient data, case reports, and reviews. Statistical analysis was performed to compare clinicopathological variables between <i>GREB1</i>- and <i>ESR1</i>-rearranged UTROSCTs. Dichotomous variables were compared by using Fisher’s exact test; continuous variables were compared by using Student’s <i>t</i>-test. A <i>p</i>-value < 0.05 was considered significant. <b>Results:</b> Six studies with 88 molecularly classified UTROSCTs were included. A total of 36 cases were <i>GREB1</i>-rearranged, and 52 cases were <i>ESR1</i>-rearranged. <i>GREB1</i>-rearranged UTROSCTs showed a significantly older age (<i>p</i> < 0.001), larger tumor size (<i>p</i> = 0.002), less common submucosal/polypoid growth (<i>p</i> = 0.005), higher mitotic index (<i>p</i> = 0.010), more common LVSI (<i>p</i> = 0.049), and higher likelihood to undergo hysterectomy (<i>p</i> = 0.008) compared to <i>ESR1</i>-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). <i>GREB1</i>-rearranged UTROSCTs showed significantly lower disease-free survival compared to <i>ESR1</i>-rearranged UTROSTCs (<i>p</i> = 0.049). <b>Conclusions:</b> In conclusion, <i>GREB1</i>-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 <i>ESR1</i>-rearranged UTROSCTs. Nonetheless, the similar immunophenotype suggests that they belong to the same tumor family. Further studies are necessary to confirm this point.https://www.mdpi.com/2075-4418/15/6/792UTROSCTs<i>GREB1</i><i>ESR1</i>clinicopathologicalimmunohistochemistry
spellingShingle 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
Clinicopathological Comparison Between <i>GREB1</i>- and <i>ESR1</i>-Rearranged Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Systematic Review
Diagnostics
UTROSCTs
<i>GREB1</i>
<i>ESR1</i>
clinicopathological
immunohistochemistry
title Clinicopathological Comparison Between <i>GREB1</i>- and <i>ESR1</i>-Rearranged Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Systematic Review
title_full Clinicopathological Comparison Between <i>GREB1</i>- and <i>ESR1</i>-Rearranged Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Systematic Review
title_fullStr Clinicopathological Comparison Between <i>GREB1</i>- and <i>ESR1</i>-Rearranged Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Systematic Review
title_full_unstemmed Clinicopathological Comparison Between <i>GREB1</i>- and <i>ESR1</i>-Rearranged Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Systematic Review
title_short Clinicopathological Comparison Between <i>GREB1</i>- and <i>ESR1</i>-Rearranged Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Systematic Review
title_sort clinicopathological comparison between i greb1 i and i esr1 i rearranged uterine tumors resembling ovarian sex cord tumors utroscts a systematic review
topic UTROSCTs
<i>GREB1</i>
<i>ESR1</i>
clinicopathological
immunohistochemistry
url https://www.mdpi.com/2075-4418/15/6/792
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