Comment on: Screening for Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) among Endometrial Cancer Patients

The Ohio State University, Columbus, Ohio, United States
Cancer Research (Impact Factor: 9.33). 11/2007; 67(19):9603. DOI: 10.1158/0008-5472.CAN-07-2308
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Available from: Albert de la chapelle, Apr 22, 2015
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    • "Addition of the methylation assay to the molecular analyses is effective for narrowing down suspected LS patients (Hampel et al. 2006; Gausachs et al. 2012; Leenen et al. 2012). Some researchers suggest that universal screening (US), which applies molecular analyses to all patients with EC, should be implemented as a highly sensitive screening method (Hampel et al. 2006; Moline et al. 2013). However, because the perspectives of LS are ambiguous and guidelines for surveillance have not been established, it is difficult to determine the clinical usefulness of US at this time. "
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    ABSTRACT: Lynch syndrome (LS) is an inherited disorder caused by a germline mutation in the DNA mismatch repair (MMR) genes and is associated with increased risk of various cancers, particularly colorectal cancer and endometrial cancer (EC). It is significant to identify LS in EC patients for prediction and prevention of the succeeding other associated cancers. However, useful LS screening guidelines for EC have not been established. The purpose of our study is to devise an efficient and practical screening strategy for LS in EC. We designed original criteria, named "APF criteria," with lenient terms (Age of onset < 50, or Personal or Family history of associated cancers) and applied it to unselected EC patients. We performed immunohistochemistry (IHC) and the methylation assay of MutL homolog 1 (MLH1) gene promoter using the tumors of patients who met our criteria, and thus selected "suspected LS" as the candidates for genetic analyses. Of 360 EC patients, 187 (51.9%) met the APF criteria, and the tumor specimens were available from 182 out of the 187 patients. IHC revealed that expression of at least one MMR protein was absent in cell nuclei of 54 (29.6%) tumors. Of 20 tumors lacking MLH1 protein expression, 14 cases were judged sporadic EC because of the hypermethylated MLH1 promoter. We thus selected 40 (11.1%) of 360 EC patients as "suspected LS." Our strategy that consists of clinical triage and the molecular analyses is expected to improve the screening efficiency and reduce the cost of LS identification in EC.
    The Tohoku Journal of Experimental Medicine 02/2015; 235(2):117-25. DOI:10.1620/tjem.235.117 · 1.35 Impact Factor
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    • "We found normal IHC expression of MMR proteins together with MSI in 3/61 cases (4.9%). Similar results were obtained by Hampel et al. 2006 (6.3%, 6/96) [13]. Moreover, we found that about 23% (14/61) "
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    ABSTRACT: Lynch syndrome (LS) is a hereditary condition that increases the risk for endometrial and other cancers. The identification of endometrial cancer (EC) patients with LS has the potential to influence life-saving interventions. We aimed to study the prevalence of LS among EC patients in our population. Universal screening for LS was applied for a consecutive series EC. Tumor testing using microsatellite instability (MSI), immunohistochemistry (IHC) for mismatch-repair (MMR) protein expression and MLH1-methylation analysis, when required, was used to select LS-suspicious cases. Sequencing of corresponding MMR genes was performed. One hundred and seventy-three EC (average age, 63 years) were screened. Sixty-one patients (35%) had abnormal IHC or MSI results. After MLH1 methylation analysis, 27 cases were considered suspicious of LS. From these, 22 were contacted and referred for genetic counseling. Nineteen pursued genetic testing and eight were diagnosed of LS. Mutations were more frequent in younger patients (<50 yrs). Three cases had either intact IHC or MSS and reinforce the need of implement the EC screening with both techniques. The prevalence of LS among EC patients was 4.6% (8/173); with a predictive frequency of 6.6% in the Spanish population. Universal screening of EC for LS is recommended.
    PLoS ONE 11/2013; 8(11):e79737. DOI:10.1371/journal.pone.0079737 · 3.23 Impact Factor
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    • "However, others [16] have found the mean age in a prospective unselected cohort to be 54 years. If an age cut-off of 50 years old had been selected instead for LS screening, 60% of patients would have been missed [17]. In fact, others have described that 25% of LS patients do not fit standard screening criteria, such as the Amsterdam, Bethesda, and SGO criteria, where age is a prominent factor (cut-off age 50) [18]. "
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    ABSTRACT: Lynch syndrome (LS), an autosomal dominant inherited cancer susceptibility syndrome, also known as hereditary non-polyposis colon cancer (HNPCC), is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes. LS is the most common presentation of hereditary colorectal cancer (CRC), accounting for about 2--5% of all CRC cases. More recently, it is found that a similar number of endometrial cancers is also due to one of the MMR gene mutations. There has been significant progress in LS-related CRC in terms of molecular pathogenesis, risks, genetic basis, and cancer prevention. In contrast, the advance about LS-related endometrial cancer (EC) is very much limited. In this commentary, we summarize the main clinicopathologic features of LS-related EC and propose universal screening for LS in individuals with endometrial cancer.
    Journal of Hematology & Oncology 03/2013; 6(1):22. DOI:10.1186/1756-8722-6-22 · 4.81 Impact Factor
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