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 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 Soluble SIGLEC5: A New Prognosis Marker in Colorectal Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3896
Author(s):  
Karla Montalbán-Hernández ◽  
Ramón Cantero-Cid ◽  
Roberto Lozano-Rodríguez ◽  
Alejandro Pascual-Iglesias ◽  
José Avendaño-Ortiz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Operating Characteristic ◽  
Prognostic Markers ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Significant Heterogeneity ◽  
Kaplan Meier ◽  
Prognosis Marker ◽  
Colorectal Cancer Patients ◽  
Healthy Participants

Colorectal cancer (CRC) is the second most deadly and third most commonly diagnosed cancer worldwide. There is significant heterogeneity among patients with CRC, which hinders the search for a standard approach for the detection of this disease. Therefore, the identification of robust prognostic markers for patients with CRC represents an urgent clinical need. In search of such biomarkers, a total of 114 patients with colorectal cancer and 67 healthy participants were studied. Soluble SIGLEC5 (sSIGLEC5) levels were higher in plasma from patients with CRC compared with healthy volunteers. Additionally, sSIGLEC5 levels were higher in exitus than in survivors, and the receiver operating characteristic curve analysis revealed sSIGLEC5 to be an exitus predictor (area under the curve 0.853; cut-off > 412.6 ng/mL) in these patients. A Kaplan–Meier analysis showed that patients with high levels of sSIGLEC5 had significantly shorter overall survival (hazard ratio 15.68; 95% CI 4.571–53.81; p ≤ 0.0001) than those with lower sSIGLEC5 levels. Our study suggests that sSIGLEC5 is a soluble prognosis marker and exitus predictor in CRC.

scholarly journals Report of a Novel Mutation inMLH1Gene in a Hispanic Family from Puerto Rico Fulfilling Classic Amsterdam Criteria for Lynch Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Juan M. Marqués-Lespier ◽  
Yaritza Diaz-Algorri ◽  
Maria Gonzalez-Pons ◽  
Marcia Cruz-Correa
Keyword(s):  
Colorectal Cancer ◽  
Puerto Rico ◽  
Lynch Syndrome ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Limited Information ◽  
Protein Coding ◽  
Genetic Sequencing ◽  
Amsterdam Criteria ◽  
Hispanic Family

In Puerto Rico, colorectal cancer (CRC) represents the second leading cause of cancer in men and women. Familial CRC accounts for 10–15% of the total CRC cases, while Lynch syndrome accounts for approximately 2–4% of cases. Limited information is available about the prevalence, clinical manifestations, and genetic mutations of hereditary CRC in US Hispanic individuals. In this paper we report a novel mutation in thehMLH1gene in a Puerto Rican Hispanic family with Lynch syndrome recruited through the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). Our proband was identified by applying Amsterdam and Bethesda criteria for Lynch syndrome, analysis of protein expression by immunohistochemistry, and genetic sequencing of the mismatch repair genes. A novel mutation at c.2044_2045 inhMLH1consisting of the deletion of two consecutive nucleotides (AT) at exon 18 was identified. This deletion causes a frameshift in the protein coding sequence at p.682 resulting in premature termination and a truncated MLH1 protein. To our knowledge, this mutation has not been previously reported in the literature. The detection of this novel mutation inMLH1further emphasizes the need for genetic testing in at-risk patients for hereditary CRC from various ethnic and racial backgrounds.

T2040 Poor Compliance with MSI-Analysis in Patients with Colorectal Cancer At High Risk for Lynch Syndrome

2008 ◽  
Vol 134 (4) ◽  
pp. A-606
Author(s):  
Margot G. van Lier ◽  
J. de Wilt ◽  
J. Wagemakers ◽  
W. Dinjens ◽  
R. Damhuis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Lynch Syndrome ◽  
Poor Compliance ◽  
Msi Analysis

scholarly journals Differential diagnosis of small bowel occlusions

2009 ◽  
Vol 3 (2) ◽  
pp. 81-87
Author(s):  
Paolo Ghiringhelli
Keyword(s):  
Colorectal Cancer ◽  
Differential Diagnosis ◽  
Lynch Syndrome ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Autosomal Dominant ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Early Age ◽  
Increased Risk ◽  
Hereditary Nonpolyposis

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, and microsatellite instability (MSI). Patients with Lynch syndrome have a markedly increased risk of colorectal cancer. We report a case of a 28-year-old male with Lynch syndrome; the case allows to describe clinical manifestations and diagnostic criteria of this syndrome, and to underline the importance of genetics in the diagnosis of this disease.

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 Prevalence and spectrum of MLH1, MSH2, and MSH6 pathogenic germline variants in Pakistani colorectal cancer patients

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Muhammad Usman Rashid ◽  
Humaira Naeemi ◽  
Noor Muhammad ◽  
Asif Loya ◽  
Jan Lubiński ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Lynch Syndrome ◽  
Research Centre ◽  
Germline Variants ◽  
Pathogenic Variants ◽  
History Of ◽  
Group 2 ◽  
Colorectal Cancer Patients ◽  
Group 1

Abstract Background Pathogenic germline variants in MLH1, MSH2 and MSH6 genes account for the majority of Lynch syndrome (LS). In this first report from Pakistan, we investigated the prevalence of pathogenic MLH1/MSH2/MSH6 variants in colorectal cancer (CRC) patients. Methods Consecutive cases (n = 212) were recruited at the Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), between November 2007 to March 2011. Patients with a family history of > 3 or 2 HNPCC-associated cancers were classified as HNPCC (n = 9) or suspected-HNPCC (n = 20), respectively (group 1; n = 29). Cases with no family history were designated as non-HNPCC (group 2; n = 183). MLH1/MSH2/MSH6 genes were comprehensively screened in group 1. Pathogenic/likely pathogenic variants identified in group 1 were subsequently evaluated in group 2. Results Eight distinct pathogenic/likely pathogenic MLH1/MSH2 variants were found in group 1 (10/29; 34.5%), belonging to HNPCC (5/9; 55.6%) and suspected-HNPCC (5/20; 25%) families and in group 2 (2/183; 1.1%) belonging to non-HNPCC. Overall, three recurrent variants (MSH2 c.943-1G > C, MLH1 c.1358dup and c.2041G > A) accounted for 58.3% (7/12) of all families harboring pathogenic/likely pathogenic MLH1/MSH2 variants. Pathogenic MSH6 variants were not detected. Conclusion Pathogenic/likely pathogenic MLH1/MSH2 variants account for a substantial proportion of CRC patients with HNPCC/suspected-HNPCC in Pakistan. Our findings suggest that HNPCC/suspected-HNPCC families should be tested for these recurrent variants prior to comprehensive gene screening in this population.

scholarly journals Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors

2004 ◽  
Vol 20 (4-5) ◽  
pp. 207-213 ◽  
Author(s):  
H. F. A. Vasen ◽  
Y. Hendriks ◽  
A. E. de Jong ◽  
M. van Puijenbroek ◽  
C. Tops ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endometrial Cancer ◽  
Gene Mutation ◽  
Molecular Analysis ◽  
Cost Effective ◽  
Preventative Measures ◽  
Amsterdam Criteria ◽  
Revised Amsterdam Criteria ◽  
Msi Analysis

Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) is a dominantly inherited syndrome characterized by the development of colorectal cancer, endometrial cancer and other cancers and the presence of microsatellite instability (MSI) in tumors. The Bethesda guidelines have been proposed for the identification of families suspected of HNPCC that require further molecular analysis. We have evaluated the yield of MSI-analysis in a large series of Dutch families suspected of HNPCC. We also analysed whether the loss of mismatch repair (MMR) protein detected by immunohistochemistry (IHC) of colorectal cancer (CRC) and endometrial cancer correlated with the presence of MSI and/or a MMR gene mutation. The results showed that the Bethesda criteria with a few modifications are appropriate to identify families eligible for genetic testing. In addition, we found that MSI and IHC-analysis of CRC using antibodies against MLH1, MSH2, MSH6 and PMS2 proteins are equally effective for identifying carriers of the known MMR gene defects. However, as long as the role of other putative MMR genes in hereditary CRC has not been elucidated, IHC-analysis cannot completely replace MSI. For this reason, we prefer MSI-analysis as first step in families suspected of HNPCC. On the other hand, in families fulfilling the revised Amsterdam criteria in which the probability of detecting a mutation is relatively high, we would recommend IHC as first diagnostic step because the result might predict the specific underlying MMR gene mutation. MSI or IHC-analysis of endometrial cancer alone was found to be less sensitive compared with these tests performed in colorectal cancer. Therefore, probably the best approach in the analysis of this cancer is to perform both techniques. The identification of HNPCC is important as it makes it possible to target effective preventative measures. Our studies showed that MSI and IHC analysis of colorectal and endometrial cancer, are reliable cost-effective tools that can be used to identify patients with HNPCC.

S1979 Routine MSI-Analysis in Colorectal Cancer Patients ≥ 70 Years Leads to the Identification of More Patients At High Risk for Lynch Syndrome

2009 ◽  
Vol 136 (5) ◽  
pp. A-306
Author(s):  
Margot G. van Lier ◽  
A. Wagner ◽  
Ernst J. Kuipers ◽  
W. Dinjens ◽  
M.E. Leerdam van ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Lynch Syndrome ◽  
Cancer Patients ◽  
Colorectal Cancer Patients ◽  
Msi Analysis

scholarly journals piRNA-823 Is a Unique Potential Diagnostic Non-Invasive Biomarker in Colorectal Cancer Patients

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 598
Author(s):  
Norhan A. Sabbah ◽  
Wael M. Abdalla ◽  
Walid A. Mawla ◽  
Nagla AbdAlMonem ◽  
Amal F. Gharib ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Serum Levels ◽  
P Element ◽  
Serum Samples ◽  
Expression Levels ◽  
Non Invasive ◽  
Colorectal Cancer Patients

Early detection of colorectal cancer (CRC) is the most important factor in deciding its prognosis, so the need to develop an accurate screening test is a must. P-element induced wimpy testis (PIWI) RNA-823 (piR-823) is one of the first piRNAs recognized to be linked to malignancy. We aimed to investigate the expression levels of piR-823 in both serum and tissues of colorectal cancer patients and the ability to use its serum level as a non-invasive diagnostic biomarker to detect colorectal cancer. We determined piR-823 expression levels in 84 serum samples of CRC patients, 75 serum samples of healthy controls, and biological specimens obtained from the 84 patients with colorectal cancer from both the tumor tissues and the normal neighboring tissues using quantitative real-time reverse transcriptase-PCR. We showed that piR-823 had significantly higher serum and tissue expression levels in CRC patients compared to the controls. We observed a significant positive correlation between piR-823 serum levels and the staging of CRC, with significantly higher levels exhibiting advanced stages of CRC (III and IV). This translates into poorer differentiation and lymph node metastasis. The receiver operating characteristic curve (ROC curve) test showed 83.3% sensitivity and 89.3% specificity at a cut-off value of >5.98-fold change, with an area under the curve of 0.933 (p < 0.0001) concerning the ability of piR-823 in diagnosing patients with colorectal carcinoma. piR-823 expression is upregulated in colorectal cancer patients’ serum and tissues, and it can be used as a diagnostic noninvasive biomarker for CRC.

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