scholarly journals Lynch syndrome I: A case report

2008 ◽  
Vol 61 (1-2) ◽  
pp. 79-82
Author(s):  
Vesna Zivkovic ◽  
Vuka Katic ◽  
Jasmina Gligorijevic ◽  
Zlatibor Andjelkovic ◽  
Aleksandar Petrovic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Case Report ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Clinical Stage ◽  
Family Members ◽  
Advanced Rectal Cancer ◽  
Degree Relative ◽  
Mmr Genes ◽  
Amsterdam Criteria

Introduction. Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndromes J and II, accounts for about 5-8% of colorectal cancers. Lynch syndrome I is an autosomal domi?nant inherited disorder characterized by early onset of colorectal cancer, predominance of proximal and multiple tumors, and microsatellite instability. In order to identify HNPCC, the international "Amsterdam criteria" have been used. Case report. The proband was a 40-year-old male who was admitted to hospital with a diagnosis of advanced rectal cancer. Left colectomy was carried out. A histopathologic diagnosis of poorly differentiated adenocarcinoma of clinical stage Dukes C was made. The family talking was done and it was revealed that the pro-band had five family members (one of first degree relative) with colorectal cancer, and two successive generations affected. All malignancy were diagnosed before 45 years of age. In one family member, metachronous transverse cancer was revealed 12 years after surgery for cecal adenocarcinoma. Discussion and conclusion. The main molecular cause for HNPCC is constitutional mutation in one of the mismatch repair (MMR) genes that regulate the excision of errors occurring during DNA replication. The most often are mutations of MLHI and MSH2 genes, and microsatellite instability is present in about 90-95% HNPCC. In this report, we present a case of an HNPCC patient who met the Amsterdam criteria for Lynch syndrome I. Family members that fulfill the Amsterdam criteria should be investigated for mutation in MMR genes. The genetic tests are not routinely available, so colonoscopic screening of all asymptomatic family members older than 25 has been recommended.

scholarly journals Clinical, anamnestic, molecular and genetic criteria for Lynch syndrome

2019 ◽  
Vol 6 (4) ◽  
pp. 38-46
Author(s):  
A. V. Semyanikhina ◽  
N. I. Pospekhova ◽  
M. G. Filippova ◽  
D. A. Golovina ◽  
A. O. Rasulov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Expression Patterns ◽  
Clinical Criteria ◽  
Mmr Genes ◽  
Leading Role ◽  
Amsterdam Criteria ◽  
Colorectal Cancer Patients ◽  
Mmr Proteins

Lynch syndrome is the most common cancer-prone syndrome associated with a high risk of colorectal cancer (CRC), neoplasms of the upper gastrointestinal system, the urinary tract, the female reproductive system, brain tumours and others. The only known form of hereditary endometrial cancer is also diagnosed as part of Lynch syndrome. One or more pathogenic germline mutations in one of the mismatch repair (MMR) genes are the cause of Lynch syndrome. Mapping of MMR genes and the discovery of microsatellite instability (MSI) have given rise to the possibility of using these clue characteristics of the pathogenic process for the elaboration of a screening test for Lynch syndrome. Being highly accurate and superior to all previously developed clinical criteria and guidelines, MSI-testing along with the assessment of the expression patterns of MMR proteins by immunohistochemistry has taken the leading role in the early diagnosis of Lynch syndrome. This article focuses on a brief review about the main evolutionary stages of clinical, anamnestic, molecular and genetic criteria for Lynch syndrome together with the results of our own research on the accuracy of the Amsterdam criteria, the Bethesda guidelines and MSI-diagnostics in the determination of the indications for MMR-genotyping in colorectal cancer patients suspected for Lynch syndrome.

scholarly journals Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients

2016 ◽  
Vol 29 (10) ◽  
pp. 587
Author(s):  
Jorge Hernâni-Eusébio ◽  
Elisabete Barbosa
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Statistical Significance ◽  
Phenotypic Correlation ◽  
Mismatch Repair Gene ◽  
Small Data ◽  
Repair Gene ◽  
Amsterdam Criteria

Introduction: Lynch syndrome is the most common form of hereditary colorectal cancer, being also responsible for endometrial and other types of cancers. It is associated with germline mutations in DNA mismatch repair genes and microsatellite instability. MLH1 and MSH2 mutations have a “classical” Lynch syndrome phenotype, with MSH2 having a higher association with extracolonic cancer. MSH6 and PMS2 mutations have an atypical phenotype. Clinical expression is heterogeneous, with correlation between mismatch repair mutated gene and phenotypic patterns.Material and Methods: We retrospectively analyzed data from patients fulfilling Amsterdam criteria or having mismatch repair gene mutations, between September 2012 and October 2015.Results: We identified 28 patients. Seventeen had colorectal cancer with right colon predominance. Five developed endometrial cancer (median age of diagnosis – 53), with no MSH6 mutations. Five developed other cancers. All mutated mismatch repair cases studied had microsatellite instability.Discussion: Most cases had MSH2 mutations despite MLH1 being described in the literature as the most frequently mutated. Interestingly, colorectal cancer patients showed no tendency for high inflammatory infiltrate. Despite the high incidence of synchronous and metachronous tumours, most patients underwent a partial colectomy. Prophylactic hysterectomy and adnexectomy was performed in menopausal/perimenopausal patients.Conclusion: A standardized registration of patient’s data may lead to better management and knowledge about Lynch syndrome. Use of Bethesda Guidelines might identify new cases non-identified by Amsterdam criteria. Microsatellite instability analysis must be performed in a much larger scale. The genotypic/phenotypic correlation described in the literature was not verified in our study with statistical significance, perhaps due to small data sample and insufficient clinical registration.

scholarly journals HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME) PADA WANITA UMUR 16 TAHUN

2011 ◽  
Vol 35 (2) ◽  
pp. 172
Author(s):  
Asril Zahari ◽  
Sudiyatmo Sudiyatmo
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Abdominal Mass ◽  
Lower Abdominal Pain ◽  
Hepatic Flexure ◽  
Amsterdam Criteria ◽  
Genetic Abnormalities ◽  
Similar Disease ◽  
History Of

AbstrakKanker kolorektal menduduki peringkat ketiga jenis kanker yang paling sering terjadi di dunia. Sekitar 3% kasus kanker kolorektal merupakan jenis hereditary non polyposis colorectal cancer (HNPCC)/Lynch syndrome, yang sering muncul pada usia muda. Dilaporkan satu kasus di rumah sakit Dr. M. Djamil Padang, wanita berumur 16 tahun dengan keluhan nyeri perut kanan bawah. Didapatkan riwayat penyakit serupa pada kakek, bibi pasien dan enam anggota keluarga yang lain. Pada pemeriksaan fisik abdomen teraba massa dengan konsistensi keras dan terfiksir. Pada kolonoskopi dan biopsi ditemukan tumor jenis adenocarcinoma colon moderatly differentiated di fleksura hepatika dan polip di kolon sigmoid. Berdasarkan kriteria Amsterdam pasien didiagnosa Lynch syndrome. Pada Pasien dilakukan subtotal kolektomi, anastomose ileorectal dan kemoterapi ajuvan. Identifikasi genetik sedang dikerjakan untuk melihat adanya kelainan genetik pada pasien. Pasien melakukan skrining berkala untuk mencegah kanker HNPCC jenis yang lain.Kata kunci : Hereditary non polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, skrining.AbstractCarcinoma colorectal is the third most common type of cancer that occurs in the world. About 2% -3% of cases of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome, which often appear at a young age. Amsterdam and Bethesda criteria have been used to identify patients with Lynch syndrome.one case was reported at the Dr. M. Djamil Padang hospital, a 16-year-old girl with right lower abdominal pain. Obtained a history of similar disease in grandparents, aunts and six other family members. On physical examination found palpable fixed abdominal mass with hard consistency in the lower right abdomen. At colonoscopy and biopsy found a moderatly differentiated adenocarcinoma colon type at the hepatic flexure and the sigmoid colon polyp. Based on the Amsterdam criteria, patients diagnosed with HNPCC/Lynch syndrome. Patients treated with subtotal colectomy, ileorectal anastomose and adjuvant chemotherapy.LAPORAN KASUS173Genetic identification is underway to see any genetic abnormalities. Patients be screened regularly to prevent other types of cancer HNPCC.Key word : Hereditary non-polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, screening.

TUMOUR PATHOLOGY PREDICTS MICROSATELLITE INSTABILITY IN A POPULATION-BASED SERIES OF COLORECTAL CANCER CASES

2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Population Based ◽  
Pathological Features ◽  
Predictive Tool ◽  
Entire Cohort ◽  
Dna Mismatch ◽  
Bethesda Guidelines ◽  
Revised Bethesda Guidelines

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56

scholarly journals Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abram Bunya Kamiza ◽  
Wen-Chang Wang ◽  
Jeng-Fu You ◽  
Reiping Tang ◽  
Huei-Tzu Chien ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Cumulative Risk ◽  
Germline Mutations ◽  
Han Chinese ◽  
Chinese Patients ◽  
Mutation Carriers ◽  
Amsterdam Criteria ◽  
Cumulative Risks ◽  
Age And Sex

AbstractPatients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

scholarly journals Performance of tumor testing for Lynch syndrome identification in patients with colorectal cancer: A retrospective single-center study

2018 ◽  
Vol 105 (1) ◽  
pp. 76-83 ◽  
Author(s):  
Stefano Signoroni ◽  
Maria Grazia Tibiletti ◽  
Maria Teresa Ricci ◽  
Massimo Milione ◽  
Federica Perrone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Characteristic Curve ◽  
Age At Onset ◽  
Area Under The Curve ◽  
Single Center ◽  
Germline Variants ◽  
Amsterdam Criteria ◽  
Clinicopathologic Parameters ◽  
Msi Analysis

Objective: To investigate the performance of tumor testing approaches in the identification of Lynch syndrome (LS) in a single-center cohort of people with colorectal cancer (CRC). Methods: A retrospective analysis of data stored in a dedicated database was carried out to identify patients with CRC suspected for LS who were referred to Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, between 1999 and 2014. The sensitivity and specificity of immunohistochemistry (IHC) for mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis (alone or combined) were calculated with respect to the presence of causative MMR germline variants. Results: A total of 683 patients with CRC suspected for LS were identified. IHC results of MMR protein analysis and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis was performed in 418 patients based on the IHC or MSI test result and/or clinical features. Univariate and multivariate analysis revealed a significant correlation of pathogenic MMR germline variants with all clinicopathologic features including Amsterdam criteria, presence of endometrial cancer, CRC site, age at onset, stage, and grade. The highest odds ratio values were observed for IHC and MSI (17.1 and 8.8, respectively). The receiver operating characteristic curve and area under the curve values demonstrated that IHC alone or combined with other clinicopathologic parameters was an excellent test for LS identification. Conclusions: This study confirms the effectiveness of tumor testing to identify LS among patients with CRC. Although IHC and MSI analysis were similarly effective, IHC could be a better strategy for LS identification as it is less expensive and more feasible.

scholarly journals Role of microsatellite instability-low as a diagnostic biomarker of Lynch syndrome in colorectal cancer

2014 ◽  
Vol 207 (10-12) ◽  
pp. 495-502 ◽  
Author(s):  
Eduardo Vilar ◽  
Maureen E. Mork ◽  
Amanda Cuddy ◽  
Ester Borras ◽  
Sarah A. Bannon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Diagnostic Biomarker

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.

Use of immunohistochemical versus microsatellite analyses as markers for colorectal cancer

2017 ◽  
Vol 43 (2) ◽  
pp. 134-141
Author(s):  
Utku Tantoğlu ◽  
Seher Yüksel ◽  
Cihangir Akyol ◽  
Haldun Doğan ◽  
Nükhet Kutlay ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immunohistochemical Analysis ◽  
Sporadic Colorectal Cancer ◽  
Molecular Tests ◽  
Antibody Panel ◽  
Mismatch Repair Proteins ◽  
Good Concordance

Abstract Objectives: Our aim was to determine how well immunohistochemical analysis identified colon cancer patients with microsatellite instability in Turkish patients. Material and methods: Subjects were patients that underwent surgery for colorectal cancer in our institution between 2006 and 2011. Patients were grouped as: (1) suspected Lynch syndrome (n=14), (2) familial colorectal cancer (n=14), and (3) sporadic colorectal cancer groups (n=14). Mismatch repair proteins were analyzed by a four antibody-panel immunohistochemistry. Microsatellite instability analysis was conducted on DNA samples using MSI-PCR followed by fragment analysis. Results: The immunohistochemistry and PCR results had good concordance in 35/42 patients. Both microsatellite instability and at least one mismatch repair protein deficiency were detected in 11 patients, and both microsatellite stability and normal expression of mismatch repair proteins were detected in 24 patients. Test results were discordant in seven of the patients. Conclusion: As it is not feasible to perform expensive molecular tests in healthcare units in many developing countries, the four antibody-panel immunohistochemistry is a reliable and affordable method for screening for colorectal cancer, including Lynch syndrome and sporadic cases when suspected.

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