Antonio Raffone1, Antonio Travaglino2, Diego Raimondo3, Maria Pia Boccellino4, Manuela Maletta5, Giulia Borghese5, Paolo Casadio5, Luigi Insabato6, Antonio Mollo7, Fulvio Zullo4, Renato Seracchioli5. 1. Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy; 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, Bologna 40138, Italy. 2. Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy. Electronic address: antonio.travaglino@unina.it. 3. 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, Bologna 40138, Italy. Electronic address: die.raimondo@gmail.com. 4. Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy. 5. 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, Bologna 40138, Italy. 6. Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy. 7. Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.
Abstract
BACKGROUND: Polymerase-ε (POLE)-mutated endometrial carcinomas (ECs) have displayed an increased number of tumor-infiltrating lymphocytes (TIL) compared to POLE-wild-type ECs. However, it is unclear if TIL may aid in identifying POLE-mutated ECs when molecular data are unavailable. The identification of a POLE mutation surrogate may be crucial to translate TCGA/ProMisE risk assessment in the clinical practice. AIM: To assess TIL as histological surrogate of POLE mutation in EC. MATERIALS AND METHODS: Seven electronic databases were searched from their inception to September 2020 for studies that allowed data extraction about TIL and TCGA/ProMisE groups of EC. We calculated pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on SROC curves of TIL in distinguishing POLE-mutated from i) POLE-wild-type, ii) no specific molecular profile (NSMP), iii) POLE-wild-type/MMR-proficient, iii) MMR-deficient ECs. RESULTS: 10 studies assessing 1169 women were included in the qualitative analysis. TIL-high pattern showed: sensitivity = 0.65, specificity = 0.63, LR + =2.06, LR- = 0.48, DOR = 4.39, AUC = 0.7532 for POLE-mutant vs POLE-wild-type ECs; sensitivity = 0.85, specificity = 0.73, LR + =2.80, LR- = 0.22, DOR = 15.17 for POLE-mutant vs NSMP ECs; sensitivity = 0.85, specificity = 0.66, LR + =2.49, LR- = 0.25, DOR = 10.30 for POLE-mutant vs POLE-wild-type/MMR-proficient ECs; sensitivity = 0.68, specificity = 0.44, LR + =1.38, LR- = 0.64, DOR = 2.68, AUC = 0.6694 for POLE-mutant vs MMR-deficient ECs. CONCLUSION: TIL-high pattern shows a moderate accuracy in distinguishing POLE-mutated from POLE-wild-type ECs after the exclusion of MMR-deficient cases. TIL might be considered in an integrate algorithm to identify POLE-mutated ECs when sequencing is unavailable. Further studies are necessary in this regard.
BACKGROUND: Polymerase-ε (POLE)-mutated endometrial carcinomas (ECs) have displayed an increased number of tumor-infiltrating lymphocytes (TIL) compared to POLE-wild-type ECs. However, it is unclear if TIL may aid in identifying POLE-mutated ECs when molecular data are unavailable. The identification of a POLE mutation surrogate may be crucial to translate TCGA/ProMisE risk assessment in the clinical practice. AIM: To assess TIL as histological surrogate of POLE mutation in EC. MATERIALS AND METHODS: Seven electronic databases were searched from their inception to September 2020 for studies that allowed data extraction about TIL and TCGA/ProMisE groups of EC. We calculated pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on SROC curves of TIL in distinguishing POLE-mutated from i) POLE-wild-type, ii) no specific molecular profile (NSMP), iii) POLE-wild-type/MMR-proficient, iii) MMR-deficient ECs. RESULTS: 10 studies assessing 1169 women were included in the qualitative analysis. TIL-high pattern showed: sensitivity = 0.65, specificity = 0.63, LR + =2.06, LR- = 0.48, DOR = 4.39, AUC = 0.7532 for POLE-mutant vs POLE-wild-type ECs; sensitivity = 0.85, specificity = 0.73, LR + =2.80, LR- = 0.22, DOR = 15.17 for POLE-mutant vs NSMP ECs; sensitivity = 0.85, specificity = 0.66, LR + =2.49, LR- = 0.25, DOR = 10.30 for POLE-mutant vs POLE-wild-type/MMR-proficient ECs; sensitivity = 0.68, specificity = 0.44, LR + =1.38, LR- = 0.64, DOR = 2.68, AUC = 0.6694 for POLE-mutant vs MMR-deficient ECs. CONCLUSION: TIL-high pattern shows a moderate accuracy in distinguishing POLE-mutated from POLE-wild-type ECs after the exclusion of MMR-deficient cases. TIL might be considered in an integrate algorithm to identify POLE-mutated ECs when sequencing is unavailable. Further studies are necessary in this regard.
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: Marco Ambrosio; Antonio Raffone; Andrea Alletto; Chiara Cini; Francesco Filipponi; Daniele Neola; Matilde Fabbri; Alessandro Arena; Diego Raimondo; Paolo Salucci; Manuela Guerrini; Antonio Travaglino; Roberto Paradisi; Antonio Mollo; Renato Seracchioli; Paolo Casadio Journal: Front Oncol Date: 2022-09-23 Impact factor: 5.738