scholarly journals Hyperplastic Polyps Are Innocuous Lesions in Hereditary Nonpolyposis Colorectal Cancers

2011 ◽  
Vol 2011 ◽  
pp. 1-7
Author(s):  
D. Speake ◽  
J. O'Sullivan ◽  
D. G. Evans ◽  
F. Lalloo ◽  
J. Hill ◽  
...  
Keyword(s):  
Protein Expression ◽  
Microsatellite Instability ◽  
Molecular Level ◽  
Colorectal Cancers ◽  
Hyperplastic Polyps ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Hereditary Nonpolyposis ◽  
Msi Analysis

Aims. To compare methylation profiles, protein expression, and microsatellite instability (MSI) of sporadic, HNPCC, and familial hyperplastic polyps (HPs).Methods. Methylation-specific PCR (MSP) and pyrosequencing assessed p16, MGMT, hMLH-1, MINT 1, and MINT 31 methylation. IHC (Immunohistochemistry) assessed Ki67, CK20, hMLH-1, hMSH-2, and hMSH-6 protein expression. MSI analysis was performed on those polyps with adequate DNA remaining.Results. 124 HPs were identified 78 sporadic, 21 HNPCC, 25 familial, and the HNPCC group demonstrated no significant differences in overall methylation (P=.186Chi2). The familial group demonstrated significantly less over all methylation levels (P=.004Chi2).Conclusions. HPs that occur in HNPCC have no more worrying features at a molecular level than those patients with HPs in a sporadic setting.

Loss of Expression of DNA Mismatch Repair Proteins Is Rare in Pancreatic and Small Intestinal Neuroendocrine Tumors

2011 ◽  
Vol 135 (12) ◽  
pp. 1539-1544 ◽  
Author(s):  
Thomas Arnason ◽  
Heidi L Sapp ◽  
Daniel Rayson ◽  
Penelope J Barnes ◽  
Magdalena Drewniak ◽  
...  
Keyword(s):  
Protein Expression ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Neuroendocrine Tumors ◽  
Dna Mismatch Repair ◽  
High Rate ◽  
Dna Mismatch ◽  
Small Intestinal ◽  
Msi Analysis ◽  
Mmr Proteins

Context.—Two recent studies have identified a high rate of microsatellite instability (MSI) in pancreatic neuroendocrine tumors (pNETs). Microsatellite instability is rare in small intestinal neuroendocrine tumors (NETs). It is unclear why there is discordance in the frequency of MSI in the 2 studies of pNETs and why this mechanism is comparatively rare in small intestinal tumors. Loss of expression of DNA mismatch repair (MMR) proteins, which is known to correlate strongly with MSI, is not well studied in pancreatic or small intestinal NETs. Objective.—To determine if there is loss of expression of MMR protein expression in pancreatic or small intestinal NETs. Design.—Sixty-nine patients (31 male, 38 female; mean age, 59.2 years) were identified who had a resection for a primary pancreatic (n  =  35) or primary small intestinal (n  =  34) NET during an 18-year period. Immunohistochemical stains for MLH1, MSH2, MSH6, and PMS2 were applied to archived tissue from all cases. All pNETs with adequate tissue (n  =  32) were also assessed by MSI analysis. Results.—There was preserved expression of MLH1, MSH2, MSH6, and PMS2 in all 35 pNETs. Of 32 pNETs tested by polymerase chain reaction, 28 were microsatellite stable and DNA did not amplify in 4. In 34 small intestinal NETs, 2 cases had indeterminate MLH1 and 1 case had indeterminate PMS2 expression. The remainder had intact MMR protein expression. Conclusion.—Defects in DNA MMR proteins are rare in pancreatic and small intestinal NETs, raising doubt that MSI plays a significant role in the pathogenesis of these tumors.

Clinicopathologic and Pedigree Differences in Amsterdam I–Positive Hereditary Nonpolyposis Colorectal Cancer Families According to Tumor Microsatellite Instability Status

2007 ◽  
Vol 25 (7) ◽  
pp. 781-786 ◽  
Author(s):  
Laura Valle ◽  
Jose Perea ◽  
Pablo Carbonell ◽  
Victoria Fernandez ◽  
Ana M. Dotor ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Repair System ◽  
Primary Tumors ◽  
Multiple Primary Tumors ◽  
Hereditary Nonpolyposis ◽  
Multiple Primary

Purpose To establish the clinicopathologic and familial differences within Amsterdam I–positive families, showing either tumor microsatellite instability (MSI) or microsatellite stability (MSS) in order to confirm or deny the existence of hereditary nonpolyposis colorectal cancer (HNPCC) without defects in the mismatch repair system. Patients and Methods Sixty-four Amsterdam I–positive families were included in the study for which full, three-generation, family medical histories and colorectal paraffin-embedded tumors were obtained. Both personal and clinicopathologic information of patients were collected. In all cases, both the MSI status and the mismatch repair (MMR) protein expression were analyzed. MMR genetic testing was performed on the MSI families. Results Of the Amsterdam I–positive families, 59.4% were tumor MSI, and 40.6% were tumor MSS. When comparing both groups, the statistical differences were observed in the age of onset (MSI, 41 years; MSS, 53 years); in the colorectal tumor location, more frequently proximal in MSI cases; in fewer mucinous tumors in MSS; and loss of MMR protein expression in the MSI tumors. Regarding the individual and familial cancer history, we observed a predominance of individuals with multiple primary tumors in MSI pedigrees, as well as differences in the type of tumors developed within the family. Conclusion Our findings support the suspicion of another hereditary colorectal syndrome different from HNPCC and characterized by MSS, the normal MMR immunohistochemical expression, the presence of only colorectal tumors, and the absence of individuals with multiple primary tumors. All these circumstances suggest the existence of a non-MMR gene being responsible for this new syndrome.

Microsatellite Instability in Colorectal Carcinoma

2003 ◽  
Vol 127 (6) ◽  
pp. 694-700 ◽  
Author(s):  
Valérie Rigau ◽  
Nicole Sebbagh ◽  
Sylviane Olschwang ◽  
François Paraf ◽  
Najat Mourra ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Screening Method ◽  
Molecular Testing ◽  
Cancer Syndrome ◽  
Simple Method ◽  
Mmr Genes ◽  
Hereditary Nonpolyposis

Abstract Context.—Microsatellite instability (MSI) due to defective mismatch repair (MMR) genes has been reported in the majority of colorectal tumors from patients with hereditary nonpolyposis colorectal cancer syndrome and in 10% to 15% of sporadic colorectal cancers. The identification of cancers associated with MSI requires classical molecular testing as the gold standard. Objective.—The aim of this study was to evaluate the role of immunohistochemistry with antibodies directed against 4 MMR proteins as a screening tool for carcinomas with MSI. Methods.—In this study, 204 formalin-fixed, paraffin-embedded colorectal carcinomas were examined for MMR protein expression (hMLH1, hMSH2, hMSH6, and hPMS2) and analyzed for MSI (MSI-H indicates at least 2 of 6 markers affected). These results were correlated with histopathologic parameters. Results.—Immunohistochemical analysis revealed that loss of expression of at least 1 protein was present in 17% of cases. One hundred percent of carcinomas that showed high instability (MSI-H) showed loss of expression of hMLH1, hMSH2, or hMSH6. Loss of expression of 2 proteins was present in 59.4% of MSI-H cases, with only 2 combinations, namely, hMLH1/hPMS2 and hMSH2/hMSH6. Isolated loss of hMSH6 expression was present in 2 MSI-H cases. Conclusions.—These findings confirm that examination of MMR protein expression by immunohistochemistry is a simple method to diagnose colorectal cancer with MSI. Our data suggest that the study of hMSH6 may be useful, in addition to hMLH1 and hMSH2. Moreover, immunohistochemistry could represent a screening method with which to direct research on the mutations of MMR genes observed in hereditary nonpolyposis colorectal cancer syndrome.

Mutations of hMLH1 and hMSH2 in Patients With Suspected Hereditary Nonpolyposis Colorectal Cancer: Correlation With Microsatellite Instability and Abnormalities of Mismatch Repair Protein Expression

2002 ◽  
Vol 20 (5) ◽  
pp. 1203-1208 ◽  
Author(s):  
Mario Scartozzi ◽  
Francesca Bianchi ◽  
Saverio Rosati ◽  
Eva Galizia ◽  
Annalisa Antolini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Germ Line ◽  
Missense Mutations ◽  
Hereditary Nonpolyposis ◽  
Germ Line Mutations

PURPOSE: The relationship between germ-line mutations of hMSH2 and hMLH1, microsatellite instability (MSI), and loss of DNA mismatch repair (MMR) gene expression were studied to formulate an effective selection protocol for patients with suspected hereditary nonpolyposis colorectal cancer who should be offered genetic testing. PATIENTS AND METHODS: Patients eligible for germ-line analysis of hMLH1 and hMSH2 were selected. Tumor specimens were obtained to assess MSI and loss of MMR gene expression. RESULTS: Among 37 patients who participated in the study, two hMSH2 and two hMLH1 missense mutations (11%) were detected, none of which was found in a panel of 60 healthy volunteers. High MSI was found in five tumors (19%) and low MSI in 10 tumors (39%); 12 tumors (46%) were microsatellite stable. Four tumors demonstrated loss of hMLH1, and three tumors demonstrated loss of hMSH2 protein expression. CONCLUSION: No relationship was found between MMR gene mutations and MSI; low or no MSI was found in the four patients with germ-line mutations, and none of the five patients with high MSI demonstrated abnormalities of MMR genes. On the contrary, loss of hMLH1 or hMSH2 expression was found in the tumors from three of the four patients demonstrating germ-line mutations. These data suggest that germ-line mutations of the MMR gene can occur in people with MSI-negative tumors. Sensitive clinical criteria and the study of MMR gene expression may be useful to identify this subset of patients.

Somatic hMLH3 frameshift mutation in colorectal cancers with microsatellite instability

2001 ◽  
Vol 120 (5) ◽  
pp. A295-A295
Author(s):  
D CHANG ◽  
A GOEL ◽  
L RICCIARDIELLO ◽  
C ARNOLD ◽  
C BOLAND
Keyword(s):  
Microsatellite Instability ◽  
Frameshift Mutation ◽  
Colorectal Cancers
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