RESUMO
BACKGROUND: Distinguishing hydatidiform moles (HMs) from nonmolar specimens and the subclassification of HM are important because complete hydatidiform mole (CHM) is associated with an increased risk of development of gestational trophoblastic neoplasia. However, diagnosis based solely on morphology has poor inter-observer reproducibility. Recent studies have demonstrated that the use of p57KIP2 immunostaining improves diagnostic accuracy for CHM. OBJECTIVES: To evaluate the accuracy of p57KIP2 immunostaining compared with molecular genotyping for the diagnosis of CHM. SEARCH STRATEGY: Major databases were searched from inception to March 2017 using the terms 'hydatidiform mole', 'p57', and 'genotyping', with their variations, and the search limit for the relevant study design. SELECTION CRITERIA: Any cross-sectional study, case series, case-control study, cohort study, or clinical trial that evaluated the accuracy of p57KIP2 immunostaining for the diagnosis of CHM compared with genotyping was included. Case reports, narrative reviews, expert opinions, and animal testing were excluded. DATA COLLECTION AND ANALYSIS: Extracted accuracy data were tabulated and pooled using a hierarchical bivariate random effects model. MAIN RESULTS: Bivariate meta-analysis produced a summary sensitivity of 0.984 (95% CI: 0.916-1.000) and specificity of 0.625 (95% CI: 0.503-0.736) with significant heterogeneity for specificity (I2 = 71.8, chi-square P = 0.029). The pooled summary diagnostic odds ratio was 56.54 (95% CI: 11.03-289.74) with no heterogeneity (I2 = 0.00%, chi-square P = 0.67). The diagnostic performance of the test was high with an area under the curve of (AUC) 0.980. CONCLUSIONS: p57KIP2 immunostaining is accurate when diagnosing CHM. It can be used as an adjunct test in a combination algorithmic approach. TWEETABLE ABSTRACT: A meta-analysis to evaluate the accuracy of p57KIP2 compared with genotyping to diagnose CHM.
Assuntos
Inibidor de Quinase Dependente de Ciclina p57/genética , Genótipo , Mola Hidatiforme/diagnóstico , Neoplasias Uterinas/diagnóstico , Feminino , Humanos , Mola Hidatiforme/genética , Imuno-Histoquímica , Gravidez , Sensibilidade e Especificidade , Neoplasias Uterinas/genéticaRESUMO
BACKGROUND: 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 p57KIP2 immunostaining improves diagnostic accuracy for CHM. METHODS: We will conduct a systematic review of prospective and retrospective studies to evaluate the accuracy of p57KIP2 immunostaining 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 I 2 statistics and explored through sensitivity analysis. DISCUSSION: 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, p57KIP2 immunostaining 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 p57KIP2 immunostaining is an adequate alternative diagnostic test for CHM. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015024181.