Antonio Travaglino1, Antonio Raffone2, Annarita Gencarelli1, Serena Saracinelli3, Carla Riccardi4, Antonio Mollo5, Fulvio Zullo4, Luigi Insabato1. 1. Anatomic 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. Electronic address: anton.raffone@gmail.com. 3. Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy; Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy. 4. Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy. 5. Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.
Abstract
BACKGROUND: Endometrial undifferentiated/dedifferentiated carcinoma (UDC/DDC) is a recently described aggressive variant of endometrial carcinoma, which shows mismatch repair (MMR) deficiency in about half of cases. AIM: To assess whether MMR-deficient UDC/DDC have distinct clinico-pathological features. MATERIALS AND METHODS: A systematic review and meta-analysis was performed by searching 4 electronic databases from their inception to October 2020 for all studies reporting clinicopathological characteristics of UDC/DDC series. Student t-test (for continuous variables), Cox regression analysis (for overall survival) and odds ratio (OR, for dichotomous variables) were used with a significant p-value < 0.05; data were pooled by using a random effect model. RESULTS: Twelve studies were included. MMR-deficiency was significantly associated with older age (p = 0.024), p53-wild-type (p = 0.005), ARID1A loss (p = 0.001) and PD-L1 expression (p = 0.019), but not with overall survival (p = 0.307), extension beyond corpus (p = 0.787) or beyond uterus (p = 0.403), presence of a differentiated component (p = 0.461), loss of expression of cytokeratins (p = 0.698), EMA (p = 0.309), estrogen receptor (p = 0.605), PAX8 (p = 0.959), SMARCA4/BRG1 (p = 0.321), SMARCB1/INI1 (p = 0.225) or claudin-4 (p = 0.094), or POLE exonuclease domain mutation p = (0.773). CONCLUSIONS: In UDC/DDC, MMR-deficiency appears associated with older age, p53-wild type and ARID1A loss, suggesting the possibility of a distinct pathway underlying dedifferentiation; the association with PD-L1 expression is attributable to the high mutational load and may have therapeutic implications. On the other hand, MMR-deficiency appears not to be associated with prognosis, stage, loss of differentiation markers or POLE mutation.
BACKGROUND:Endometrial undifferentiated/dedifferentiated carcinoma (UDC/DDC) is a recently described aggressive variant of endometrial carcinoma, which shows mismatch repair (MMR) deficiency in about half of cases. AIM: To assess whether MMR-deficient UDC/DDC have distinct clinico-pathological features. MATERIALS AND METHODS: A systematic review and meta-analysis was performed by searching 4 electronic databases from their inception to October 2020 for all studies reporting clinicopathological characteristics of UDC/DDC series. Student t-test (for continuous variables), Cox regression analysis (for overall survival) and odds ratio (OR, for dichotomous variables) were used with a significant p-value < 0.05; data were pooled by using a random effect model. RESULTS: Twelve studies were included. MMR-deficiency was significantly associated with older age (p = 0.024), p53-wild-type (p = 0.005), ARID1A loss (p = 0.001) and PD-L1 expression (p = 0.019), but not with overall survival (p = 0.307), extension beyond corpus (p = 0.787) or beyond uterus (p = 0.403), presence of a differentiated component (p = 0.461), loss of expression of cytokeratins (p = 0.698), EMA (p = 0.309), estrogen receptor (p = 0.605), PAX8 (p = 0.959), SMARCA4/BRG1 (p = 0.321), SMARCB1/INI1 (p = 0.225) or claudin-4 (p = 0.094), or POLE exonuclease domain mutation p = (0.773). CONCLUSIONS: In UDC/DDC, MMR-deficiency appears associated with older age, p53-wild type and ARID1A loss, suggesting the possibility of a distinct pathway underlying dedifferentiation; the association with PD-L1 expression is attributable to the high mutational load and may have therapeutic implications. On the other hand, MMR-deficiency appears not to be associated with prognosis, stage, loss of differentiation markers or POLE mutation.
Authors: Vanessa M López-Ozuna; Liron Kogan; Mahmood Y Hachim; Emad Matanes; Ibrahim Y Hachim; Cristina Mitric; Lauren Liu Chen Kiow; Susie Lau; Shannon Salvador; Amber Yasmeen; Walter H Gotlieb Journal: Front Oncol Date: 2021-07-07 Impact factor: 6.244
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