Antonio Raffone1, Ursula Catena2, Antonio Travaglino3, Valeria Masciullo2, Saveria Spadola4, Luigi Della Corte5, Alessia Piermattei2, Luigi Insabato6, Gian Franco Zannoni7, Giovanni Scambia2, Fulvio Zullo1, Giuseppe Bifulco1, Francesco Fanfani2, Attilio Di Spiezio Sardo8. 1. Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy. 2. Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy. 3. Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy. Electronic address: antonio.travaglino.ap@gmail.com. 4. Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 5. Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy; Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy. 6. Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy. 7. Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Rome, Italy. 8. Department of Public Health, University of Naples Federico II, Naples, Italy.
Abstract
OBJECTIVE: Deficient expression of mismatch repair proteins (MMR) has been suggested to be a predictor of resistance of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EEC) to conservative treatment. AIMS: To assess the predictive value of MMR immunohistochemistry in patients conservatively treated for AEH and EEC, and to calculate its predictive accuracy. MATERIALS AND METHODS: All patients with AEH or EEC conservatively treated with hysteroscopic resection plus progestins in two referral centers from January 2004 to July 2019 were retrospectively assessed. Immunohistochemistry for MMR was ad hoc performed. Study outcomes were: (i) the association of a deficient immunohistochemical expression of MMR with resistance and recurrence of AEH and EEC after conservative treatment, and (ii) the accuracy of MMR immunohistochemistry in predicting the outcome of conservative treatment. Relative risk (RR) for the associations, and sensitivity, specificity and area under the curve (AUC) on receiver operating characteristic curve for the predictive accuracy were calculated. RESULTS: Sixty-nine women, (47 AEH and 22 EEC) were included; deficient MMR expression was observed in 8.7% of cases. Resistance to conservative treatment was more common in MMR-deficient than MMR-proficient cases (33.3% vs 15.9%; RR = 2.1), but with no statistical significance (p = 0.2508). On the other hand, recurrence was significantly more common in MMR-deficient than MMR-proficient cases (100% vs 26.4%; RR = 3.8; p < 0.0001). In predicting recurrence, a deficient immunohistochemical expression of MMR showed sensitivity = 22.2%, specificity = 100%, and AUC = 0.61. CONCLUSION: Deficient MMR immunohistochemical expression does not imply resistance of AEH/EEC to conservative treatment. On the other hand, MMR-deficiency appears as a highly specific predictor of recurrence of AEH/EEC after initial regression.
OBJECTIVE: Deficient expression of mismatch repair proteins (MMR) has been suggested to be a predictor of resistance of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EEC) to conservative treatment. AIMS: To assess the predictive value of MMR immunohistochemistry in patients conservatively treated for AEH and EEC, and to calculate its predictive accuracy. MATERIALS AND METHODS: All patients with AEH or EEC conservatively treated with hysteroscopic resection plus progestins in two referral centers from January 2004 to July 2019 were retrospectively assessed. Immunohistochemistry for MMR was ad hoc performed. Study outcomes were: (i) the association of a deficient immunohistochemical expression of MMR with resistance and recurrence of AEH and EEC after conservative treatment, and (ii) the accuracy of MMR immunohistochemistry in predicting the outcome of conservative treatment. Relative risk (RR) for the associations, and sensitivity, specificity and area under the curve (AUC) on receiver operating characteristic curve for the predictive accuracy were calculated. RESULTS: Sixty-nine women, (47 AEH and 22 EEC) were included; deficient MMR expression was observed in 8.7% of cases. Resistance to conservative treatment was more common in MMR-deficient than MMR-proficient cases (33.3% vs 15.9%; RR = 2.1), but with no statistical significance (p = 0.2508). On the other hand, recurrence was significantly more common in MMR-deficient than MMR-proficient cases (100% vs 26.4%; RR = 3.8; p < 0.0001). In predicting recurrence, a deficient immunohistochemical expression of MMR showed sensitivity = 22.2%, specificity = 100%, and AUC = 0.61. CONCLUSION: Deficient MMR immunohistochemical expression does not imply resistance of AEH/EEC to conservative treatment. On the other hand, MMR-deficiency appears as a highly specific predictor of recurrence of AEH/EEC after initial regression.
Authors: Anna Franca Cavaliere; Federica Perelli; Simona Zaami; Marco D'Indinosante; Irene Turrini; Marco Giusti; Giuseppe Gullo; Giuseppe Vizzielli; Alberto Mattei; Giovanni Scambia; Annalisa Vidiri; Fabrizio Signore Journal: Int J Mol Sci Date: 2021-11-12 Impact factor: 5.923