Clinicopathologic Characteristics of Endometrial Cancer in Lynch Syndrome

Rossi, L.; Frère‐Belda, Marie‐Aude Le; Laurent‐Puig, Pierre; Bruno, Benedetto; Pauw, Antoine de; Stoppa‐Lyonnet, Dominique; Canlorbe, Geoffroy; Caron, Olivier; Borghese, Bruno; Colas, Chrystelle; Delhomelle, Hélène; Chabbert-Buffet, Nathalie; Grandjouan, S.; Lécuru, Fabrice; Bats, Anne-Sophie

doi:10.1097/igc.0000000000000985

Cited by 40 publications

(49 citation statements)

References 38 publications

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“…Variants in the PMS2 gene were rarer. This finding is consistent with reports from investigations of EC as a component tumor from identified LS families . Predominant MSH6 gene mutations were also reported when the LS screening was conducted in cohorts of EC patients .…”

Section: Discussionsupporting

confidence: 91%

“…However, a standardized and objective interpretation for this assay remains challenging. Regarding other clinical features, the majority of the ECs were endometrioid (87%), Grades 1 and 2 (40% for both), and Stage I (74%) with at least 24% with lower segment localization, consistent with previously reported data . However, none of these characteristics seemed to be informative.…”

Section: Discussionsupporting

confidence: 88%

“…This finding is consistent with reports from investigations of EC as a component tumor from identified LS families. 30,39,40 Predominant MSH6 gene mutations were also reported when the LS screening was conducted in cohorts of EC patients. 13,41 Thus, our study suggested that genetic alterations in MSH2, MSH6 and MLH1 genes constitute an important contribution to EC in the Chinese population.…”

Section: Mutational Characteristics In Ec Related Cancer Syndromesmentioning

confidence: 91%

“…Regarding other clinical features, the majority of the ECs were endometrioid (87%), Grades 1 and 2 (40% for both), and Stage I (74%) with at least 24% with lower segment localization, consistent with previously reported data. [30][31][32] However, none of these characteristics seemed to be informative. Nevertheless, certain histology types such as carcinosarcoma, mucinous, neuroendocrine or serous were unlikely to be associated with LS.…”

Section: Clinical and Pathological Criteria For Identifying Ls Patientsmentioning

confidence: 99%

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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: 91%

Section: Discussionsupporting

confidence: 88%

Section: Mutational Characteristics In Ec Related Cancer Syndromesmentioning

confidence: 91%

Section: Clinical and Pathological Criteria For Identifying Ls Patientsmentioning

confidence: 99%

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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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“…In one case‐control study including 69 women with Lynch syndrome‐associated EC, almost 20% were diagnosed at 40 years or younger . Women with Lynch syndrome‐associated EC have similar outcomes to sporadic EC and have a similar incidence of low‐grade endometrioid histology . However, Lynch‐associated EC arises more frequently in the lower uterine segment (LUS) instead of the uterine corpus, which may increase the likelihood of high‐grade histology.…”

Section: Lynch Syndromementioning

confidence: 99%

Screening and surgical prophylaxis for hereditary cancer syndromes with high risk of endometrial and ovarian cancer

Bercow

Eisenhauer

2019

Journal of Surgical Oncology

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In the era of advanced cancer genomics, our recognition of hereditary cancer mutations continues to increase. Two of these conditions, which carry an increased risk of female cancers including endometrial, ovarian, breast, are hereditary breast and ovarian cancer syndrome and Lynch syndrome. Risk-reducing surgery, such as mastectomy, salpingo-oophorectomy, and hysterectomy may decrease cancer risk for mutation carriers. Background, indications, techniques, and consequences of these surgical procedures are reviewed.BRCA, endometrial cancer, hereditary cancer, Lynch syndrome, ovarian cancer | INTRODUCTIONIn 2019, over 109 000 women in the United States will be diagnosed with gynecologic malignancy and over 33 000 will die from one. 1 Although only a small percentage of these women will develop endometrial or ovarian cancer associated with an identifiable germline mutation, the potential for personalized prevention and individualized treatment is great in this select cohort. This article will review the hereditary conditions associated with increased risk of ovarian and/or endometrial cancer and how patients should be screened for these mutations. It will also address the surgical means by which these women can reduce their risk of ovarian and endometrial cancer. | HEREDITARY BREAST AND OVARIAN CANCER SYNDROMEIn 2018, approximately 22 000 women received a new diagnosis of ovarian cancer in the United States, and there were 14 000 ovarian cancer deaths. 2 Inherited germline mutations that increase the risk for ovarian cancer are present in approximately 7%-25% of these women. 3 Hereditary breast and ovarian cancer syndrome (HBOC) is the most common genetic syndrome linked to ovarian cancer and is associated with mutations in the BRCA genes. BRCA1 and BRCA2 are tumor suppressor genes involved in the repair of double-stranded DNA breaks. Certain populations are at significantly higher risk for BRCA mutations than the general population including, Ashkenazi Jewish, French Canadian, and Icelandic populations. This is because of the founder effect, which causes a decrease in genetic diversity in a population that is geographically or reproductively isolated. For example, in the general United States non-Jewish population, the risk of inheriting a BRCA mutation is 1 in 400 compared with the Ashkenazi Jewish population, who carry an increased risk of 1 in 40. 4 The inheritance pattern of the BRCA mutations is autosomal dominant. However, tumor suppressor genes are known to be recessive, requiring both copies of the gene to be affected. In the "two-hit" hypothesis, a loss of heterozygosity is required. Therefore, a germline BRCA mutation is inherited in one copy of the gene, the second copy then undergoes a somatic mutationi.e., the second hitand the carrier is phenotypically affected. 5The most recently estimated cumulative cancer risk by age 80 for BRCA1 and BRCA2 carriers is 72% and 69%, respectively. 2 By comparison, the lifetime risk of ovarian and breast cancer in the general population is 1.3% and 12.4%, respective...

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Ultrasound and blind endometrial sampling for detection of endometrial cancer in women with postmenopausal bleeding

Vikram,

Robinson,

Thanawala

et al. 2024

Cochrane Database of Systematic Reviews

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Clinicopathologic Characteristics of Endometrial Cancer in Lynch Syndrome

Abstract: The LS-associated EC is characterized by a young age at onset, a high prevalence of lower uterine segment involvement, and synchronous ovarian cancers. The prognosis of these cancers does not appear different from sporadic tumors.

Cited by 40 publications

References 38 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

Screening and surgical prophylaxis for hereditary cancer syndromes with high risk of endometrial and ovarian cancer

Ultrasound and blind endometrial sampling for detection of endometrial cancer in women with postmenopausal bleeding

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