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Apoptotic index for prediction of postmolar gestational trophoblastic neoplasia
| Content Provider | Scilit |
|---|---|
| Author | Braga, Antonio Maestá, Izildinha Soares, Renan Rocha Elias, Kevin M. Domingues, Maria Aparecida Custódio Barbisan, Luis Fernando Berkowitz, Ross S. |
| Copyright Year | 2016 |
| Description | Journal: American Journal of Obstetrics and Gynecology Although 85% of patients with a complete hydatidiform mole (CHM) achieve spontaneous remission after a few months, 15% will develop gestational trophoblastic neoplasia (GTN), which requires chemotherapy. To date, there is no biomarker to predict post-molar GTN prior to initiating human chorionic gonadotropin (hCG) surveillance.To assess the relationship between the expression of apoptosis markers in the molar villous trophoblasts and the subsequent development of GTN following evacuation of a complete hydatidiform mole.This is a retrospective cohort study of patients with CHM, who were diagnosed, treated, and followed at the Center of Trophoblastic Diseases (Botucatu/São Paulo State and Rio de Janeiro/Rio de Janeiro State, Brazil) between 1995 and 2014. Patients were divided temporally into derivation (1995-2004) and validation (2005-2014) cohorts. Immunohistochemistry was used to examine tissue expression of the apoptosis inhibitor survivin or the pro-apoptotic enzyme caspase-3. Survivin stains for cytoplasmic and nuclear expression were evaluated independently. Caspase-3 expression was measured as an apoptotic index of positive staining cells over negative staining cells multiplied by 100. Receiver operating characteristic (ROC) curves were then constructed, and the area under the curve (AUC) calculated to test the performance characteristics of the staining to predict the subsequent development of GTN.The final study population comprised 780 patients, with 390 patients in each temporal cohort; 590 patients entered spontaneous remission, and 190 patients developed post-molar GTN. Neither nuclear nor cytoplasmic survivin expression performed well as a predictor of subsequent GTN. The caspase-3 apoptotic index was a strong risk factor for subsequent GTN development. When the apoptotic index was <4%, the risk of GTN had an odds ratio of 35.55 (95% confidence interval [CI] 14.02-90.14; p <0.0001) in the derivation cohort and an odds ratio of 25.71 (95% CI 10.13-65.29; p <0.0001) in the validation cohort. While in both cohorts the positive predictive value for GTN of an apoptotic index < 4.0% was modest (49% in the derivation cohort and 41% in the validation cohort), the negative predictive value for GTN of an apoptotic index ≥ 4.0% was high (97% in both cohorts).The subsequent development of GTN following evacuation of CHM is closely tied to the apoptotic index, and this may be a useful biomarker for future prospective studies. |
| Related Links | https://repositorio.unesp.br/bitstream/11449/161876/1/WOS000382495100026.pdf http://www.ajog.org/article/S0002937816300515/pdf |
| ISSN | 00029378 |
| e-ISSN | 10976868 |
| DOI | 10.1016/j.ajog.2016.04.010 |
| Journal | American Journal of Obstetrics and Gynecology |
| Issue Number | 3 |
| Volume Number | 215 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2016-04-16 |
| Access Restriction | Open |
| Subject Keyword | Journal: American Journal of Obstetrics and Gynecology Complete Hydatidiform Mole Gestational Trophoblastic Neoplasia Immunohistochemistry Receiver Operating Characteristic |
| Content Type | Text |
| Resource Type | Article |
| Subject | Obstetrics and Gynecology |