Antonio Travaglino1, Antonio Raffone2, Angela Santoro3, Diego Raimondo4, Giuseppe Angelico5, Michele Valente5, Damiano Arciuolo5, Giulia Scaglione5, Nicoletta D'alessandris5, Paolo Casadio4, Frediano Inzani5, Antonio Mollo6, Renato Seracchioli7, Gian Franco Zannoni8. 1. Gynecopathology and Breast Pathology Unit, Department of Woman's Health Science, Agostino Gemelli University Polyclinic, Rome, Italy; Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy. 2. Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy; Division of Gynecology 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, Bologna 40138, Italy. Electronic address: antonio.raffone@unina.it. 3. Gynecopathology and Breast Pathology Unit, Department of Woman's Health Science, Agostino Gemelli University Polyclinic, Rome, Italy. Electronic address: angela.santoro@policlinicogemelli.it. 4. Division of Gynecology 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, Bologna 40138, Italy. 5. Gynecopathology and Breast Pathology Unit, Department of Woman's Health Science, Agostino Gemelli University Polyclinic, Rome, Italy. 6. Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy. 7. Division of Gynecology 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, Bologna 40138, Italy. Electronic address: renato.seracchioli@unibo.it. 8. Gynecopathology and Breast Pathology Unit, Department of Woman's Health Science, Agostino Gemelli University Polyclinic, Rome, Italy; Catholic University of Sacred Heart, Rome, Italy.
Abstract
INTRODUCTION: In the ESGO/ESTRO/ESP guidelines for endometrial carcinoma management, the risk category of clear cell carcinoma (CCC) is not well defined. In fact, while p53-abnormal (p53abn) CCC are known to be aggressive, the prognosis of mismatch repair-deficient (MMRd) and p53-wild-type (p53wt) CCCs is less clear. OBJECTIVE: To assess the prognostic value of the MMRd and p53wt groups in CCC through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to February 2021. All studies reporting p53 expression, MMR proteins expression and survival outcomes in endometrial CCC (either pure or mixed) were included. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) for overall survival (OS) were performed by using the p53abn group as reference; a significant p-value<0.05 was adopted. RESULTS: Six studies with 136 CCC (114 pure and 22 mixed) were included. Five-year OS was 95.7 ± 4.3% in the MMRd group, 48.4 ± 8.4% months in the p53wt group and 40.6 ± 10.4% in the p53abn group. The hazard of death was significantly lower in the MMRd group than in the p53abn group (HR = 0.062; p = 0.007), while it did not significantly differ between the p53wt and the p53abn group (HR = 0.673; p = 0.222). The POLEmut group could not be analyzed due to the absence of deaths. Similar results were observed in the pure CCC and mixed CCC subgroups. CONCLUSION: MMRd CCCs seem to have a favorable prognosis and might be lumped together with MMRd endometrioid carcinoma for management purpose. On the other hand, p53wt CCCs appear prognostically more similar to p53abn CCCs.
INTRODUCTION: In the ESGO/ESTRO/ESP guidelines for endometrial carcinoma management, the risk category of clear cell carcinoma (CCC) is not well defined. In fact, while p53-abnormal (p53abn) CCC are known to be aggressive, the prognosis of mismatch repair-deficient (MMRd) and p53-wild-type (p53wt) CCCs is less clear. OBJECTIVE: To assess the prognostic value of the MMRd and p53wt groups in CCC through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to February 2021. All studies reporting p53 expression, MMR proteins expression and survival outcomes in endometrial CCC (either pure or mixed) were included. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) for overall survival (OS) were performed by using the p53abn group as reference; a significant p-value<0.05 was adopted. RESULTS: Six studies with 136 CCC (114 pure and 22 mixed) were included. Five-year OS was 95.7 ± 4.3% in the MMRd group, 48.4 ± 8.4% months in the p53wt group and 40.6 ± 10.4% in the p53abn group. The hazard of death was significantly lower in the MMRd group than in the p53abn group (HR = 0.062; p = 0.007), while it did not significantly differ between the p53wt and the p53abn group (HR = 0.673; p = 0.222). The POLEmut group could not be analyzed due to the absence of deaths. Similar results were observed in the pure CCC and mixed CCC subgroups. CONCLUSION: MMRd CCCs seem to have a favorable prognosis and might be lumped together with MMRd endometrioid carcinoma for management purpose. On the other hand, p53wt CCCs appear prognostically more similar to p53abn CCCs.
Authors: Antonio Raffone; Antonio Travaglino; Diego Raimondo; Manuela Maletta; Valentino De Vivo; Umberto Visiello; Paolo Casadio; Renato Seracchioli; Fulvio Zullo; Luigi Insabato; Antonio Mollo Journal: Int J Gynaecol Obstet Date: 2021-12-11 Impact factor: 4.447