title: Accuracy of p57KIP2compared with genotyping for the diagnosis of complete hydatidiform mole: protocol for a systematic review and meta-analysis.
abstract: Distinguishing hydatidiform moles (HMs) from non-molar specimens and the subclassification of HM are important because complete hydatidiform mole (CHM) is associated with an increased risk of gestational trophoblastic neoplasia. However, diagnosis based solely on morphology has poor interobserver reproducibility. Recent studies have demonstrated that the use of p57KIP2immunostaining improves diagnostic accuracy for CHM.
  
  
  
  We will conduct a systematic review of prospective and retrospective studies to evaluate the accuracy of p57KIP2immunostaining compared with molecular genotyping for the diagnosis of CHM. A high-sensitivity search strategy will be employed in MEDLINE, EMBASE, LILACS, The Grey Literature Report, OpenGrey, OAIster, and Cochrane CENTRAL. Two reviewers will independently screen all identified references for eligibility and extract data. The methodological quality and bias of the included studies will be assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool, and the overall quality of evidence will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. If a meta-analysis is possible, pooled estimates of sensitivity, specificity, and positive and negative likelihood ratios will be calculated using bivariate random-effects models. Statistical heterogeneity will be evaluated with I2statistics and explored through sensitivity analysis.
  
  
  
  There is considerable overlap between the histological features of molar and non-molar pregnancies and between complete and partial HMs, which results in significant interobserver variability in the diagnosis of CHM and its mimics. Therefore, molecular techniques are used to correctly diagnosis and treat CHM. However, these molecular diagnostic methods are technically difficult to perform, relatively costly, and unavailable in most pathology laboratories. According to our results, p57KIP2immunostaining appears to be a practical and accurate adjunct for the diagnosis of CHM and its mimics because this technique is relatively simple, reliable, cost-efficient, and rapid. This systematic review will help to determine whether p57KIP2immunostaining is an adequate alternative diagnostic test for CHM.
  
  
  
  PROSPERO CRD42015024181.
authors.affiliation: School of Medicine, Center for Biological and Health Sciences - CCBS, Caxias do Sul University - UCS, Rua Francisco Getúlio Vargas, 1130, Bloco S, Caxias do Sul, RS, CEP 95070-560, Brazil. jmmadi@ucs.br.|Maternity School, Federal University of Rio de Janeiro - UFRJ, Rua das Laranjeiras, 180, Rio de Janeiro, RJ, CEP 22240-003, Brazil. jmmadi@ucs.br.
authors.forename: Jose Mauro
authors.initials: JM
authors.lastname: Madi
authors.affiliation: Maternity School, Federal University of Rio de Janeiro - UFRJ, Rua das Laranjeiras, 180, Rio de Janeiro, RJ, CEP 22240-003, Brazil.|School of Medicine, Federal University Fluminense - UFF, Niterói, RJ, Brazil.
authors.forename: Antonio Rodrigues
authors.initials: AR
authors.lastname: Braga
authors.affiliation: HIV/AIDS Research Laboratory - LPHA, Center for Biological and Health Sciences - CCBS, Caxias do Sul University - UCS, Rua Francisco Getúlio Vargas, 1130, Bloco S, Sala 315, Caxias do Sul, RS, CEP 95070-560, Brazil.
authors.forename: Machline Paim
authors.initials: MP
authors.lastname: Paganella
authors.affiliation: School of Medicine, Center for Biological and Health Sciences - CCBS, Caxias do Sul University - UCS, Rua Francisco Getúlio Vargas, 1130, Bloco S, Caxias do Sul, RS, CEP 95070-560, Brazil.
authors.forename: Isnard Elman
authors.initials: IE
authors.lastname: Litvin
authors.affiliation: Department of Public Health, Federal University of Health Science of Porto Alegre - UFCSPA, Rua Sarmento Leite, 245, Porto Alegre, RS, CEP 90050-170, Brazil.
authors.forename: Eliana Márcia
authors.initials: EM
authors.lastname: Da Ros Wendland
mesh_terms: D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics*; D003955:Diagnostic Tests, Routine / Q000592:standards; D005260:Female; D005838:Genotype; D006801:Humans; D006828:Hydatidiform Mole / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015203:Reproducibility of Results; D000078202:Systematic Reviews as Topic; D014594:Uterine Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015201:Meta-Analysis as Topic
chemical_list: D050761:Cyclin-Dependent Kinase Inhibitor p57
keywords: Complete hydatidiform mole; Meta-analysis; Molecular genotyping; Protocol; Systematic review; p57 immunohistochemistry