Assessment of the Potential Diagnostic Role of Anaplastic Lymphoma Kinase for Inflammatory Myofibroblastic Tumours: A Meta-Analysis

April Assessment of the Potential Diagnostic Role of Anaplastic Lymphoma Kinase for Inflammatory Myofibroblastic Tumours: A Meta-Analysis Shuiqing Wu 0 1 Ran Xu 0 1 Qi Wan 0 1 Xuan Zhu 0 1 Lei Zhang 0 1 Hongyi Jiang 0 1 Xiaokun Zhao 0 1 0 1 Department of Urology, The Second Xiangya Hospital of Central South University , Changsha , China , 2 Neural Medical Center of the First Hospital in Changsha City , Changsha , China 1 Academic Editor: Robert S. Phillips, University of York, UNITED KINGDOM Eight studies were included according to our inclusion criteria. The overall results for the specificity, sensitivity, PLR, NLR, DOR and area under the curve (AUC) were 0.99 (95% CI 0.82-1.00), 0.67 (95% CI 0.46-0.83), 0.67 (95% CI 0.46-0.83), 60.6 (95% CI 3.3-1112.4), 0.33 (95% CI 0.19-0.60), 181 (95% CI 9-3684) and 0.95 (95% CI 0.93-0.97), respectively, while the specificity, sensitivity, PLR, NLR, DOR and AUC for bladder IMTs were 0.99 (95% CI 0.67-1.00), 0.86 (95% CI 0.58-0.96), 95.6 (95% CI 2.0-4616.2), 0.14 (95% CI 0.04-0.50), 671 (95% CI 16-28913) and 0.99 (95% CI 0.97-0.99), respectively. - Competing Interests: The authors have declared that no competing interests exist. To assess the value of anaplastic lymphoma kinase for the diagnosis of inflammatory myofibroblastic tumours using a comprehensive meta-analysis. We searched the related literature using electronic databases and manual searches. Approximately 454 cases from several countries were included in this analysis. The quality of studies included was assessed by QUADAS (quality assessment of studies of diagnostic accuracy). The diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), sensitivity and specificity were calculated to assess the role of anaplastic lymphoma kinase in the diagnosis of inflammatory myofibroblastic tumours. The overall test performance was summarised by an SROC (summary receiver operating characteristic curve). The heterogeneity and publication bias were analysed using Meta-regression and Deeks' test. All data were analysed by Stata 12.0 software. The present meta-analysis indicated that anaplastic lymphoma kinase plays a significant role in the differential diagnosis of inflammatory myofibroblastic tumours, particularly for inflammatory myofibroblastic tumours of the urinary bladder. Inflammatory myofibroblastic tumours (IMT), also referred to as inflammatory pseudotumours, plasma cell granulomas, etc., are characterised by a fascicular proliferation of myofibroblasts with admixed inflammatory cells derived from mesenchymal tissue [1]. IMTs are rare entities, and the disease incidence of these tumours remains unclear. These tumours can arise in the respiratory and genitourinary system, particularly in the lung and bladder; however, IMTs have also been reported in other sites [23]. IMTs are considered borderline tumours, indicating an intermediate biological potential for recurrence or metastasis [4]. However, their clinical and pathological manifestations mimic malignancy; therefore, it is difficult but important to differentiate IMTs from other soft tumours. A false diagnosis may cause great harm to patients [5]. Therefore, the discovery of a potential biomarker to improve the diagnostic accuracy of IMTs is imperative. IMT diagnosis remains challenging due to overlapping immunohistochemical and morphological characteristics. The anaplastic lymphoma kinase (ALK) is detected in the majority of IMTs and is negative in several other soft tissue tumours. The ALK gene is located on chromosome 2p23 and belongs to the insulin receptor family of tyrosine kinases [6]. Since the discovery of 2p rearrangements in IMTs in 1999 [7], ALK has been considered a promising biomarker for improving the diagnostic accuracy of IMT, specifically during differential diagnosis. However, controversy remains concerning the diagnostic role of ALK in the diagnosis of IMTs. We performed a primary meta-analysis to assess the potential diagnostic role of anaplastic lymphoma kinase for Inflammatory Myofibroblastic Tumours. Materials and Methods Search strategy and study selection A comprehensive literature search for suitable studies published before July 23, 2014 was conducted in the following electronic databases, Pubmed, Embase, Web of Science, Cochrane Library and 3 Chinese databases: Wan Fang, Chinese National Knowledge Infrastructure (CNKI), Chinese Biology (CBM), and a manual search in the medical library of the Central South University. Studies that investigated the diagnostic role of anaplastic lymphoma kinase in inflammatory myofibroblastic tumour (IMT) diagnosis were included in this meta-analysis. Studies had to be published as a full paper with a publish date prior to July 2014 but with no lower date limit. The search was conducted using the following keywords: anaplastic lymphoma kinase or ALK or ALK-1, inflammatory myofibroblastic tumour or inflammatory pseudotumour or IMT and diagnostic value or diagnosis or ROC curve or sensitivity or specificity. Inclusion and exclusion criteria Studies eligible for inclusion in this meta-analysis met the following criteria: (1) studies regarding the diagnostic role of anaplastic lymphoma kinase for inflammatory myofibroblastic tumour; (2) when duplicate articles were published, only the newest or most informative single article was selected; (3) studies provided sufficient data for the construction of 2-by-2 tables, including true positive (TP), false positive (FP), true negative (TN), and false negative (FN). The exclusion criteria were as follows: (1) studies did not include raw data, such as reviews, letters, case reports, conference abstracts and editorials; (2) publications not related to the diagnostic role of anaplastic lymphoma kinase for inflammatory myofibroblastic tumour; (3) there was no control group in the study. Data extraction and quality assessment Two reviewers (SQW and LZ) independently extracted the following data from all of the included articles: author, publication year, country, location, detection method, the number of patients diagnosed with IMT, the number of controls, sample size, true positive (TP), false positive (FP), true negative (TN), false negative (FN), specificity, sensitivity. The studies were assessed for methodological quality according to the QUADAS (quality assessment of diagnostic accuracy studies) criteria [8]; one of these items, the avoidance of disease progression bias, was not included because it was not relevant to this study. Each item is answered with yes, no, or unclear response. An answer of no or unclear indicates that the risk of bias may be high and an answer of yes indicates that the risk of bias is low. An additional reviewer (XKZ) assessed all discrepancies and the majority opinion was used to resolve disagreements between the reviewers. The standard methods recommended for diagnostic accuracy meta-analysis were used in this study [9]. We extracted the numbers of part (...truncated)