scholarly journals Relationship of lower uterine segment cancer with Lynch syndrome: A novel case with an hMLH1 germline mutation

2012 ◽  
Vol 28 (5) ◽  
pp. 1537-1543 ◽  
Author(s):  
KENTA MASUDA ◽  
KOUJI BANNO ◽  
AKIRA HIRASAWA ◽  
MEGUMI YANOKURA ◽  
KOSUKE TSUJI ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Germline Mutation ◽  
Lower Uterine Segment ◽  
Relationship Of

Carcinoma of the lower uterine segment diagnosed with Lynch syndrome based on MSH6 germline mutation: A case report

2016 ◽  
Vol 43 (2) ◽  
pp. 416-420 ◽  
Author(s):  
Masataka Adachi ◽  
Kouji Banno ◽  
Kenta Masuda ◽  
Megumi Yanokura ◽  
Moito Iijima ◽  
...  
Keyword(s):  
Case Report ◽  
Lynch Syndrome ◽  
Germline Mutation ◽  
Lower Uterine Segment

scholarly journals A NovelMLH1Initiation Codon Mutation (c.3G>T) in a Large Chinese Lynch Syndrome Family with Different Onset Age and mRNA Expression Level

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yanni Zhang ◽  
Huishuang Chen ◽  
Zhiyu Peng ◽  
Santasree Banerjee ◽  
Wei Li ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Mrna Expression ◽  
Germline Mutation ◽  
Peripheral Blood ◽  
Expression Level ◽  
Onset Age ◽  
Mrna Expression Level ◽  
Increased Risk ◽  
Lynch Syndrome Family ◽  
Codon Mutation

Lynch syndrome is a genetically and clinically heterogeneous disorder; it is caused by a germline mutation in DNA mismatch repair (MMR) genes. Individuals with a heterozygous mutation in MLH1 have an increased risk for developing colorectal cancer. Here we described a 5-generation Chinese Lynch syndrome family with different severity and onset age. A novel heterozygous germline mutation (c.3G>T, p.Met1Ile) inMLH1gene was discovered by next generation sequencing. Our study also revealed by qPCR that the MLH1 mRNA expression in peripheral blood of patients in this family was remarkably lower than that of the unaffected carriers and non-carriers. The research results indicated that the mRNA expression level may provide predictive suggestions of treatment and management for carriers with the initiation codon mutation ofMLH1in this family. Further studies are undertaken in this family as well as other families with Lynch syndrome to interrogate the exact reasons affecting the MLH1 mRNA expression level and whether mRNA expression in peripheral blood could be a significant factor for early diagnosis and surveillance of Lynch syndrome.

scholarly journals PMS2 germline mutation c.943C>T (p.Arg315*)‐induced Lynch syndrome‐associated ovarian cancer

2019 ◽  
Vol 7 (6) ◽  
Author(s):  
Xiaoqing Guo ◽  
Weimin Wu ◽  
Hao Gao ◽  
Xiaofeng Li ◽  
Qizhi He ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lynch Syndrome ◽  
Germline Mutation

Prospective Determination of Prevalence of Lynch Syndrome in Young Women With Endometrial Cancer

2007 ◽  
Vol 25 (33) ◽  
pp. 5158-5164 ◽  
Author(s):  
Karen H. Lu ◽  
John O. Schorge ◽  
Kerry J. Rodabaugh ◽  
Molly S. Daniels ◽  
Charlotte C. Sun ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Germline Mutation ◽  
Age Of Onset ◽  
Cancer Syndrome ◽  
Degree Relative ◽  
Entire Cohort ◽  
Tumor Studies ◽  
The Mean

Purpose Age younger than 50 years at the time of colon cancer diagnosis is often used as a screening criterion for Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). The purpose of this study was to determine the prevalence of MLH1, MSH2, and MSH6 mutations in an unselected cohort of women diagnosed with endometrial cancer at age younger than 50 years. Methods A prospective, multicenter study was performed at three institutions. After written consent was obtained, germline mutation testing by full sequencing and large deletion analysis of the MLH1, MSH2, and MSH6 genes was performed. Tumor studies included immunohistochemistry of MLH1, MSH2, and MSH6; microsatellite instability analysis; and hypermethylation of the MLH1 promoter. Results Of the 100 women, nine (9%; 95% CI, 4.2 to 16.4) carried a deleterious germline mutation: seven women with mutations in MSH2, one woman with a mutation in MLH1, and one woman with a mutation in MSH6. Two additional women had molecular studies consistent with the diagnosis of Lynch syndrome. The mean body mass index (BMI) for the entire cohort was 34.4, which is significantly higher than 29.2, the mean BMI for the mutation carriers. Predictors of finding a germline mutation included having a first-degree relative with a Lynch syndrome–associated cancer, endometrial tumor with loss of MSH2 expression, tumors with high microsatellite instability, and lower BMI. Conclusion In this prospective study of endometrial cancer patients younger than age 50 years, 9% were found to carry germline Lynch syndrome–associated mutations. In addition to young age of onset, family history, BMI, and molecular tumor studies can improve the likelihood of identifying a Lynch syndrome–associated germline mutation in MLH1, MSH2, and MSH6.

Prognosic value of lower uterine segment involvement in high-grade endometrial cancers.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5092-5092
Author(s):  
Paola A. Gehrig ◽  
Leslie Horn Clark ◽  
Jason Franasiak ◽  
Victoria Lin Bae-Jump ◽  
Emily Ko
Keyword(s):  
Clear Cell ◽  
Early Stage ◽  
Cohort Analysis ◽  
Myometrial Invasion ◽  
Lower Uterine Segment ◽  
High Grade ◽  
Retroperitoneal Node ◽  
Endometrial Cancers ◽  
Grade 3 ◽  
Relationship Of

5092 Background: To determine the relationship of lower uterine segment (LUS) involvement and clinical-pathologic outcomes in high grade endometrial cancers (EC). Although LUS and prognosis has been previously reported in the literature, the results have been conflicting and limited to early stage cases without focus upon the highest risk histologies. Methods: A single-institution retrospective cohort analysis of all grade 3 EC from Jan 2005- Sept 2010 was performed. Clinical-pathologic data were abstracted. LUS status was determined based on permanent-section pathology. Statistical analyses were performed using univariate and bivariate analyses with t-tests, X2, and log-rank tests. Multivariate regressions were performed by cox modeling. Two sided p-values<0.05 were considered significant. Results: Of 329 cases, 52% were LUS+. Mean age was 66.1(SD 10.8) and BMI 31.7(SD 8.3). The majority were Caucasian (63.2%) and 30.1% were African-American (AA). Most women (80.2%) were overweight or obese, 58.7% had hypertension, and 22.5% were diabetic. Most women had stage I disease (54.8%), but 8.6% had stage II disease, and 36.6% had stage III-IV disease. Histologic subtypes included 32.2% endometrioid, 47.4% serous/clear cell, and 17% carcinosarcoma. Thirty-nine percent had > 50% myometrial invasion (MI) and 43.2% had LVSI. Most of the women (80.8%) underwent retroperitoneal node dissection (77.9% pelvic, 70.0% periaortic). Mean follow-up time was 24.5 months (range 0.13, 73.3). Age, HTN, and DM did not differ by LUS status. Statistically significant factors associated with LUS positivity included race AA (38.3 v 26.5%), obesity (57.5 v 46.7%), serous/clear cell (65.7 v 53.8%), LVSI (56.2 v 30.5%), deep MI (52.1 v 25.3%), and positive nodes (42.4 v 12.7%). LUS+ was significantly associated with an increased rate of recurrence (HR 2.3, CI 1.16-4.47, p =0.02) after adjusting for obesity, deep MI, LVSI, nodal status, stage, serous/clear cell histology, and adjuvant therapy. Conclusions: Lower uterine segment was independently associated with an increased rate of recurrence in high grade EC. This should be confirmed in prospective endometrial trials to see if this remains an independent predictor of recurrence.

Improving detection of Lynch syndrome using a reflex immunohistochemistry algorithm for all patients with newly diagnosed colorectal cancer.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 98-98
Author(s):  
Minggui Pan ◽  
Elizabeth Hoodfar ◽  
JoAnn Bergoffen ◽  
Regan Fulton ◽  
Laura Hofmeister ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Germline Mutation ◽  
Detection Rate ◽  
Promoter Hypermethylation ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Newly Diagnosed ◽  
Mlh1 Promoter ◽  
Mmr Proteins

98 Background: Identifying patients with Lynch syndrome has profound impact on the clinical care of patients and their families. Previous guidelines based on family history alone have shown low sensitivity. In our medical center, the detection rate of Lynch syndrome was <1% among colorectal cancer cases. Methods: We have developed a system-based algorithm using centralized testing by immunohistochemistry (IHC) for four mismatched repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2) as a screening method for all newly diagnosed colorectal cancer patients, followed by step wise testing of BRAF mutation, MLH1 promoter hypermethylation, +/- microsatellite instability, and germline mutation. Results: From April 1, 2011, to July 11, 2012, we have screened 116 patients. IHC detected absent expression of at least one of the MMR proteins in 18 cases. Three cases showed missing expression of MSH2/MSH6 and the presence of a germline mutation in MSH6 was confirmed in two cases. The newest case is still being investigated for germline mutation. Of the remaining 15 cases, 10 showed the presence of BRAF V600E mutation, two showed hypermethylation of the MLH1 promoter, and one showed germline MLH1 mutation. Two cases showed no BRAF V600E mutation, no MLH1 promoter hypermethylation or germline gene mutation. Overall, of 116 cases, three cases have confirmed Lynch syndrome with the detection of a germline mutation, two cases most likely have Lynch syndrome but without any detectable germline mutation of MLH1 or PMS2 using the current detecting methods. Conclusions: Our system-based screening algorithm using reflex immunohistochemistry of four MMR proteins has resulted in excellent detection rate of approximately 4% to 5% (5 out of 116 cases), consistent with the expected Lynch syndrome prevalence rate in the population. This represents a marked improvement over our previous family history-based approach in Lynch syndrome screening.

scholarly journals Synchronous endometrial and ovarian cancer in Lynch syndrome with a MSH2 germline mutation: A case report

2018 ◽  
Author(s):  
Takashi Takeda ◽  
Kouji Banno ◽  
Megumi Yanokura ◽  
Mayuka Anko ◽  
Arata Kobayashi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Case Report ◽  
Lynch Syndrome ◽  
Germline Mutation

scholarly journals Imaging-based definition of lower uterine segment carcinoma to improve the detection sensitivity of probable Lynch syndrome

2020 ◽  
Vol 50 (3) ◽  
pp. 270-275
Author(s):  
Hiroyuki Yamazaki ◽  
Sho Takeshita ◽  
Yukiharu Todo ◽  
Hiroko Matsumiya ◽  
Chisa Shimada ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Lynch Syndrome ◽  
Lower Uterine Segment ◽  
Broad Sense ◽  
Detection Sensitivity ◽  
Pathological Examination ◽  
Narrow Sense ◽  
Resonance Imaging ◽  
Definition Of

Abstract Objective The aim of this study was to investigate a magnetic resonance imaging-based definition of lower uterine segment carcinoma. Methods We retrospectively reviewed 587 consecutive patients with endometrial cancer who underwent hysterectomy. Lower uterine segment carcinoma was determined through pathological examination and magnetic resonance imaging assessment. For imaging assessment, the location of the inner lining of the uterus was classified into four equal parts on a sagittal section image. A tumor was defined as lower uterine segment carcinoma when its thickest part was located in the second or the third part from the uterine fundus. Lower uterine segment carcinoma was further divided into lower uterine segment in a narrow sense, upon which diagnosis was exclusively based on pathological findings, and lower uterine segment in a broad sense that were the remaining lower uterine segment carcinomas except lower uterine segment carcinomas in a narrow sense. The relationship between lower uterine segment carcinoma and probable Lynch syndrome was investigated. Patients with loss of MSH2, MSH6, and PMS2 expression or those with tumors with loss of MLH1 and absence of MLH1 promoter methylation were diagnosed as probable Lynch syndrome. Results Lower uterine segment carcinoma was identified in 59 (10.2%) patients. Twenty-eight (47.5%) patients were categorized as lower uterine segment in a narrow sense and 31 (52.5%) as lower uterine segment in a broad sense. Among them, probable Lynch syndrome was identified in 12 (20.3%) cases. There was no difference in clinical profiles, including the prevalence of probable Lynch syndrome between the two categories. Conclusions A magnetic resonance imaging-based expanded definition of lower uterine segment carcinoma is likely to secure characteristics equivalent to a conventional pathology-based definition of lower uterine segment carcinoma. The novel definition of lower uterine segment carcinoma might improve the detection of probable Lynch syndrome.

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