The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis

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Abstract

<div class="section"> <a class="named-anchor" id="d16813446e250">  </a> <h5 class="section-title" id="d16813446e251">Purpose</h5> <p id="Par1">Endometrial cancer (EC) is often the sentinel cancer in women with Lynch syndrome (LS). However, efforts to implement universal LS screening in EC patients have been hampered by a lack of evidence detailing the proportion of EC patients that would be expected to screen positive for LS. </p> </div><div class="section"> <a class="named-anchor" id="d16813446e255">  </a> <h5 class="section-title" id="d16813446e256">Methods</h5> <p id="Par2">Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. <i>I</i> <sup>2</sup> score was used to assess heterogeneity across studies. </p> </div><div class="section"> <a class="named-anchor" id="d16813446e265">  </a> <h5 class="section-title" id="d16813446e266">Results</h5> <p id="Par3">Fifty-three studies, including 12,633 EC patients, met the inclusion criteria. The overall proportion of endometrial tumors with microsatellite instability or mismatch repair (MMR) deficiency by immunohistochemistry (IHC) was 0.27 (95% confidence interval [CI] 0.25–0.28, <i>I</i> <sup>2</sup>: 71%) and 0.26 (95% CI 0.25–0.27, <i>I</i> <sup>2</sup>: 88%), respectively. Of those women with abnormal tumor testing, 0.29 (95% CI 0.25–0.33, <i>I</i> <sup>2</sup>: 83%) had LS-associated pathogenic variants on germline testing; therefore around 3% of ECs can be attributed to LS. Preselection of EC cases did increase the proportion of germline LS diagnoses. </p> </div><div class="section"> <a class="named-anchor" id="d16813446e285">  </a> <h5 class="section-title" id="d16813446e286">Conclusion</h5> <p id="Par4">The current study suggests that prevalence of LS in EC patients is approximately 3%, similar to that of colorectal cancer patients; therefore our data support the implementation of universal EC screening for LS. </p> </div>

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Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

David Moher, Alessandro Liberati, Jennifer Tetzlaff … (2009)

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Quantifying heterogeneity in a meta-analysis.

Julian P T Higgins, Simon G Thompson (2002)

The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity. Copyright 2002 John Wiley & Sons, Ltd.

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Endometrial cancer.

Philippe Morice, Alexandra Leary, Carien Creutzberg … (2016)

Endometrial cancer is the most common gynaecological tumour in developed countries, and its incidence is increasing. The most frequently occurring histological subtype is endometrioid adenocarcinoma. Patients are often diagnosed when the disease is still confined to the uterus. Standard treatment consists of primary hysterectomy and bilateral salpingo-oophorectomy, often using minimally invasive approaches (laparoscopic or robotic). Lymph node surgical strategy is contingent on histological factors (subtype, tumour grade, involvement of lymphovascular space), disease stage (including myometrial invasion), patients' characteristics (age and comorbidities), and national and international guidelines. Adjuvant treatment is tailored according to histology and stage. Various classifications are used to assess the risks of recurrence and to determine optimum postoperative management. 5 year overall survival ranges from 74% to 91% in patients without metastatic disease. Trials are ongoing in patients at high risk of recurrence (including chemotherapy, chemoradiation therapy, and molecular targeted therapies) to assess the modalities that best balance optimisation of survival with the lowest adverse effects on quality of life.