Identifying Lynch Syndrome in Women Presenting With Endometrial Carcinoma Under the Age of 50 Years

Anagnostopoulos, A. N.; McKay, Vicky H.; Cooper, Iris; Campbell, Fiona; Greenhalgh, Lynn; Kirwan, John

doi:10.1097/igc.0000000000000962

Cited by 17 publications

(18 citation statements)

References 36 publications

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“…One patient carried two mutations respectively in the BRCA1 and PMS2 genes with the phenotypes related to both LS and HBOC syndromes. The frequency of LS in our patients under 50 years of age was similar to that in a recent report from UK patients but higher than the frequency reported earlier in USA patients (9%) . This discordance might be explained by the difference in BMI between two ethnic populations.…”

Section: Discussionsupporting

confidence: 84%

Screening for hereditary cancers in patients with endometrial cancer reveals a high frequency of germline mutations in cancer predisposition genes

Tian

Ren

et al. 2019

Intl Journal of Cancer

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As inherited genetic alterations are important etiological factors causing endometrial cancer (EC), our study aimed to outline the ethnic‐related prevalence and the associated clinical and biological characteristics of germline mutations in cancer predisposition genes in Chinese EC patients. One hundred ninety‐eight Chinese EC patients were screened for germline mutations in a panel of cancer susceptibility genes using next‐generation sequencing combined with multiplex ligation‐dependent probe amplification. First, we found that among patients under 50 years of age, 26% (18/69) carried germline genetic mutations, all involving mismatch repair (MMR) genes except for one mutation affecting BRCA1. Second, when we focused on Lynch syndrome (LS) with additional selected patients, 45 were identified to carry pathogenic mutations in MMR genes, with a higher frequency found in MSH2 and MSH6. We found that age at onset, personal and familial history together with immunohistochemical assay results were the most useful criteria for the diagnosis of LS although limitations in routine practice and the sensitivity and specificity of each parameter should be taken into account. One pathogenic mutation in the PALB2 gene was detected in a patient with no breast cancer in her family. Interestingly, we identified a family carrying pathogenic variant in both PMS2 and BRCA1 genes with distinct clinical phenotypes. Multigene panel testing should be recommended to patients based on their clinical information and tumor phenotype. Our study also showed the genetic complexity in EC, which requires further investigations.

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Section: Discussionsupporting

confidence: 84%

Screening for hereditary cancers in patients with endometrial cancer reveals a high frequency of germline mutations in cancer predisposition genes

Tian

Ren

et al. 2019

Intl Journal of Cancer

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“…MSI due to MLH1 hypermethylation was not identified in studies that performed MSI analysis alone. Eleven studies did not report data on MLH1 analysis, of which seven did not perform any MLH1 methylation analysis (Supplementary Table 2) [15,16,18,19,21,33,34,37,39,40,41].…”

Section: Discussionmentioning

confidence: 99%

“…The mean age and BMI were weighted based on the number of patients per study. Four studies had inclusion criteria of patients less than 50-year old, and therefore were excluded from calculation of mean age [15][16][17][18]. Only studies that reported a number of patients with a mean age/ BMI value were included in calculation of mean age and BMI for each group.…”

Section: Strategy For Search and Selection Criteriamentioning

confidence: 99%

Clinicopathologic features of endometrial cancer with mismatch repair deficiency

Gordhandas¹,

Kahn²,

Gamble³

et al. 2020

ecancer

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The inclusion of DNA mismatch repair (MMR) evaluation as a standard of care for endometrial cancer management will result in a growing population of patients with MMR deficiency and negative germline Lynch syndrome testing (MMR-deficient). In this systematic review and study, the clinicopathologic features of endometrial cancer in patients with MMR-intact, MLH1 methylation positive, MMR-deficient or Lynch syndrome are evaluated. A systematic search of online databases between 1990 and 2018 identified studies of endometrial cancer patients with tumour testing (MMR protein immunohistochemistry or microsatellite instability) and germline assessment for Lynch syndrome. Extracted data included tumour testing, germline genetic testing, age, body mass index (BMI), family history, tumour stage, grade and histologic type. Associations between MMR-intact, MLH1 methylation positive, MMR-deficient and Lynch syndrome groups were analysed using descriptive statistics. The comprehensive search produced 4,400 publications, 29 met inclusion criteria. A total of 7,057 endometrial cancer cases were identified, 1,612 with abnormal immunohistochemistry, 977 with microsatellite instability. Nine-hundred patients underwent germline genetic testing, identifying 212 patients with Lynch syndrome. Patients in the Lynch syndrome and MMR-deficient groups were significantly younger than patients in the MMR-intact and MLH1 methylation positive groups. Patients with MMR-intact tumours had the highest BMI, followed by MMRdeficient, then Lynch syndrome. MMR-intact tumours were more likely to be grade I at diagnosis than other groups. Patients with Lynch syndrome and MMR-deficient tumours were less likely to have stage I disease as compared to patients with MMR-intact tumours. Endometrial cancer patients with MMR-deficient tumours have similar features to those with germline Lynch syndrome mutations, including age, grade, histology and stage. Even in the absence of a germline mutation, tumour evaluation for MMR status may have important clinical implications.

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“…The mean age at diagnosis was 41.6 years. In another study by Anagnostopoulos et al (22), MMR germline mutation test was performed and they identified 3 pathogenic MMR mutations in 3 of 35 patients with endometrial cancer under age 50 (8.5%; 3/35).…”

Section: Discussionmentioning

confidence: 99%

Targeted Next-Generation Sequencing of MLH1, MSH2, and MSH6 Genes in Patients with Endometrial Carcinoma under 50 Years of Age

Özdemir¹,

Alan²,

Şancı³

et al. 2019

Balkan Med J

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Identifying Lynch Syndrome in Women Presenting With Endometrial Carcinoma Under the Age of 50 Years

Cited by 17 publications

References 36 publications

Screening for hereditary cancers in patients with endometrial cancer reveals a high frequency of germline mutations in cancer predisposition genes

Screening for hereditary cancers in patients with endometrial cancer reveals a high frequency of germline mutations in cancer predisposition genes

Clinicopathologic features of endometrial cancer with mismatch repair deficiency

Targeted Next-Generation Sequencing of MLH1, MSH2, and MSH6 Genes in Patients with Endometrial Carcinoma under 50 Years of Age

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