A novel germline mutation in hMLH1 in three Korean women with endometrial cancer in a family of Lynch syndrome: case report and literature review

Abstract Background Endometrial cancer is often the sentinel cancer in women with Lynch syndrome, among which endometrioid endometrial cancer is the most common. We found a Korean case of uterine carcinosarcoma associated with Lynch syndrome. And we reviewed 27 Korean women with endometrial cancer associated with Lynch syndrome already released in case report so far. Case presentation The proband, a 45-year-old Korean woman received treatment for endometrioid adenocarcinoma. Her older sister and niece were treated for endometrioid adenocarcinoma and carcinosarcoma, respectively. Family history met the Amsterdam II criteria and immunohistochemical analysis revealed a loss of MLH1 and PMS2. They all harbored a previously unreported germline likely pathogenic variant in c.1367delC in MLH1. They underwent staging operations including total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymph node dissection, and washing cytology. All three women were healthy without evidence of relapse for over 4 years. Conclusion This report indicates a novel germline c.1367delC variant in MLH1, and presents a Korean case of uterine carcinosarcoma associated with Lynch syndrome. Furthermore, the c.1757_1758insC variant in MLH1 was suggested as a founder mutation in Lynch syndrome in Korean women.

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Lynch syndrome-related non-endometrioid endometrial cancer: analysis of outcomes

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000824 ◽

2019 ◽

Vol 30 (1) ◽

pp. 56-61

Author(s):

Giorgio Bogani ◽

Maria Grazia Tibiletti ◽

Maria Teresa Ricci ◽

Ileana Carnevali ◽

Viola Liberale ◽

...

Keyword(s):

Endometrial Cancer ◽

Lynch Syndrome ◽

Disease Free Survival ◽

Oncologic Outcomes ◽

Cox Models ◽

Matching Algorithm ◽

Pathogenic Variants ◽

Propensity Matching ◽

Endometrioid Endometrial Cancer

ObjectiveWomen with Lynch syndrome have a risk up to 40–60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer.MethodsData from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case–control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models.ResultsOverall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1–295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls.ConclusionsNon-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.

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Metachronous Uterine Endometrioid Adenocarcinoma and Peritoneal Mesothelioma in Lynch Syndrome: A Case Report

International Journal of Surgical Pathology ◽

10.1177/1066896916680745 ◽

2016 ◽

Vol 25 (3) ◽

pp. 253-257 ◽

Cited By ~ 5

Author(s):

Yuxin Lu ◽

Sara Milchgrub ◽

Gaurav Khatri ◽

Purva Gopal

Keyword(s):

Case Report ◽

Lynch Syndrome ◽

Peritoneal Mesothelioma ◽

Endometrioid Adenocarcinoma

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Carcinoma of the Lower Uterine Segment: A Newly Described Association With Lynch Syndrome

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.6296 ◽

2008 ◽

Vol 26 (36) ◽

pp. 5965-5971 ◽

Cited By ~ 131

Author(s):

Shannon N. Westin ◽

Robin A. Lacour ◽

Diana L. Urbauer ◽

Rajyalakshmi Luthra ◽

Diane C. Bodurka ◽

...

Keyword(s):

Endometrial Cancer ◽

Lynch Syndrome ◽

Endometrial Carcinoma ◽

Lower Uterine Segment ◽

Endometrioid Adenocarcinoma ◽

Clinicopathologic Characteristics ◽

Endocervical Adenocarcinoma ◽

Case Comparison ◽

Pathology Reports ◽

Clinical Records

Purpose Endometrial carcinoma in the lower uterine segment (LUS) is a poorly described cancer that can be clinically confused with endocervical carcinoma. We performed a case-comparison study to document the clinicopathologic characteristics of LUS tumors and their association with risk factors for endometrial cancer. Patients and Methods The clinical records and pathology reports from women who underwent hysterectomy at our institution for endometrial or endocervical adenocarcinoma over an 11-year interval were reviewed. The LUS group consisted of women with endometrial tumors that clearly originated between the lower uterine corpus and the upper endocervix. Immunohistochemistry and microsatellite instability and MLH1 methylation assays were performed. Results Thirty-five (3.5%) of 1,009 women had endometrial carcinoma of the LUS. Compared with patients with corpus tumors, LUS patients were younger, had higher stage tumors, and had more invasive tumors. Preoperative diagnosis of the LUS tumors more frequently included the possibility of endocervical adenocarcinoma. Seventy-three percent of the LUS tumors had an immunohistochemical expression pattern typical of conventional endometrioid adenocarcinoma. Ten (29%) of 35 women with LUS tumors were confirmed to have Lynch syndrome or were strongly suspected to have Lynch syndrome on the basis of tissue-based molecular assays. Conclusion The prevalence of Lynch syndrome in patients with LUS endometrial carcinoma (29%) is much greater than that of the general endometrial cancer patient population (1.8%) or in endometrial cancer patients younger than age 50 years (8% to 9%). On the basis of our results, the possibility of Lynch syndrome should be considered in women with LUS tumors.

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Lynch syndrome type II associated endometrial carcinoma: a case report and literature analysis

10.22541/au.163684106.64785891/v1 ◽

2021 ◽

Author(s):

hui juan Lu

Keyword(s):

Colorectal Cancer ◽

Endometrial Cancer ◽

Case Report ◽

Lynch Syndrome ◽

Autosomal Dominant ◽

Gene Mutations ◽

Hereditary Disease ◽

Syndrome Type ◽

Type Ii ◽

Literature Analysis

Lynch syndrome (LS) is an autosomal dominant hereditary disease, which is caused by mismatch repair (MMR) gene mutations in the germline of MLH1, MSH2, MSH6 and PMS2. LS patients can develop colorectal cancer, endometrial cancer (EC), etc, at the same or different time, so their prognosis are poor.

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Poster 377 The Mystery Case of the Edematous and Painful Foot: Refractory Lower Limb Complex Regional Pain Syndrome (CRPS) in the Setting of Lymphedema in a Patient with Endometrial Cancer and Lynch Syndrome: A Case Report

PM&R ◽

10.1016/j.pmrj.2016.07.304 ◽

2016 ◽

Vol 8 (9) ◽

pp. S284

Author(s):

Michelle Chi ◽

Isaac P. Syrop ◽

Jonas M. Sokolof

Keyword(s):

Endometrial Cancer ◽

Case Report ◽

Lynch Syndrome ◽

Complex Regional Pain Syndrome ◽

Lower Limb ◽

Pain Syndrome

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Isolated port-site metastasis after surgical staging for low-risk endometrioid endometrial cancer: A case report

Oncology Letters ◽

10.3892/ol.2016.4595 ◽

2016 ◽

Vol 12 (1) ◽

pp. 281-284 ◽

Cited By ~ 2

Author(s):

DANIELE MAUTONE ◽

ANDREA DALL'ASTA ◽

MICHELA MONICA ◽

LETIZIA GALLI ◽

VITO ANDREA CAPOZZI ◽

...

Keyword(s):

Endometrial Cancer ◽

Case Report ◽

Port Site ◽

Low Risk ◽

Surgical Staging ◽

Port Site Metastasis ◽

Endometrioid Endometrial Cancer

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Clinicopathologic characteristics of endometrial cancer in Lynch syndrome.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.5098 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 5098-5098

Author(s):

Fabrice Lecuru ◽

Julie Bouquier ◽

marie-Aude le Frere-Belda ◽

Cherazade Bensaid ◽

Claude Nos ◽

...

Keyword(s):

Endometrial Cancer ◽

Lynch Syndrome ◽

Age At Onset ◽

Lower Uterine Segment ◽

High Rate ◽

Serous Carcinoma ◽

Endometrioid Adenocarcinoma ◽

Clinicopathologic Characteristics ◽

Stage Ib

5098 Background: Poor data exist on clinico-pathological description of endometrial cancer (EC) in Lynch syndrome (LS) compared with sporadic ones. To evaluate the clinico-pathological findings of Lynch-related EC to establish histological criteria to discriminate familial and sporadic EC and to decide the optimal management of patients. Methods: Retrospective study of prospective cohort of patients with LS in our institution from 1999 to 2011. We identified and described all cases of endometrial cancers. Management and follow-up were detailed. Results: Of a cohort of 126 patients with LS, 10 women developed endometrial carcinoma. The median age at diagnosis was 51 years (41-58). Five patients had an identified mutation (2 hMLH1, 2 hMSH2 and 1 hMSH6). In 9 cases, EC was the first Lynch-related tumor to occur. No patient developed ovarian cancer. All, except 2 patients (1 serous carcinoma and 1 clear cell carcinoma), had endometrioid adenocarcinoma (80%). Tumor grade was grade 1 in 3 patients, grade 2 in 5 and grade 3 in 2 patients. Forty per cent of patients had lymphovascular space involvement (LVSI). The FIGO stages were as follows: stage IA (n=7), stage IB (n=2) and stage IIIC (n=1). Four in ten patients had tumor located in the lower uterine segment. With a median follow-up of 14 months (range 9 – 40 months), recurrence occurred in one patient with a stage IB grade 2 endometrioid adenocarcinoma with LVSI. Conclusions: EC in LS is characterized by early age at onset, localization in lower uterine segment, and high rate of LVSI. Other data on histology and survival do not differ from sporadic cancers. These results suggest that we can consider conservative treatment in patients with good prognosis tumors. Further studies are required.

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Impact of gene-specific germline pathogenic variants on presentation of endometrial cancer in Lynch syndrome

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-000277 ◽

2019 ◽

Vol 29 (4) ◽

pp. 705-710 ◽

Cited By ~ 3

Author(s):

Giorgio Bogani ◽

Maria Teresa Ricci ◽

Marco Vitellaro ◽

Antonino Ditto ◽

Valentina Chiappa ◽

...

Keyword(s):

Endometrial Cancer ◽

Lynch Syndrome ◽

Cancer Diagnosis ◽

European Society ◽

Medical Oncology ◽

Final Analysis ◽

Pathogenic Variants ◽

Endometrioid Endometrial Cancer ◽

The Impact ◽

Repair Genes

ObjectiveLynch syndrome is a risk factor for developing endometrial carcinoma. Our aim was to evaluate the impact of gene-specific germline pathogenic variants on clinical features of patients affected by endometrial cancer.MethodsPatients with a diagnosis of endometrial cancer and with a germline pathogenic variant in mismatch repair genes were reviewed. Patients were classified on the basis of classes of risk according to the ESGO-ESGO-ESTRO (European Society of Medical Oncology/European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology) guidelines. One-way analysis of variance (ANOVA) and Kruskal-Wallis test were performed to compare three groups of continuous parametric and non-parametric variables, respectively. χ2 test was used to analyze proportions.ResultsOverall, 68 patients with endometrial cancer and Lynch syndrome were evaluated. Ten (14.7%) patients were excluded because of absence of information about the gene involved in Lynch syndrome, thus leaving 58 (85.3%) patients available for the final analysis. MLH1, MSH2, and MSH6 pathogenic variants were observed in 19 (32.7%), 33 (56.9%), and six (10.3%) patients, respectively. Mean±SD age at endometrial cancer diagnosis was 51±6.4, 43.5±7.4, and 60.3±8.8 years (p=0.0002). Prevalence of non-endometrioid endometrial cancer was 15.7%, 24.2%, and 0% in the MLH1, MSH2, and MSH6 groups, respectively (p=0.345). According to the ESMO-ESGO-ESTRO classification, low, intermediate, and high risk endometrial cancer accounted for 47.3%, 10.5%, and 42.1% of the MLH1 group, 57.6%, 3%, and 39.4% of the MSH2 group, and 50%, 50%m and 0% of the MSH6 group (p=0.009).ConclusionsPatients with MLH1 and MSH2 pathogenic variants are at a higher risk of early onset of endometrial cancer than patients with MSH6 pathogenic variants.

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