Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas

Chapusot, Caroline; Martin, Laurent; Bouvier, Anne–Marie; Bonithon‐Kopp, Claire; Ecarnot-Laubriet, Aline; Rageot, David; Ponnelle, Tibor; Laurent‐Puig, Pierre; Faivre, Jean; Piard, F

doi:10.1038/sj.bjc.6600474

Cited by 53 publications

(47 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Identical samples will yield the most valid correlation between immunohistochemical and MSI results. Indeed, discordant tissue samples, such as fresh frozen tissue for MSI testing and paraffin block of different tumor areas for IHC, have been the reason for discordant results in certain cases [10,62], and the highest correlation between immunohistochemical and MSI testing has been demonstrated when identical tissue samples were used for both methods using microdissection techniques [10].…”

Section: Technical Factorsmentioning

confidence: 98%

The utility of immunohistochemical detection of DNA mismatch repair gene proteins

2004

View full text Add to dashboard Cite

Since the development of monoclonal antibodies against the MSH2 protein by Leach et al. in 1996, a series of investigations has been undertaken to determine the utility of immunohistochemical detection of DNA mismatch repair (MMR) gene proteins in the identification of hereditary or sporadic colorectal tumors with microsatellite instability. These studies, however, have been performed with different aims and on different patient populations. Interpretation of these immunohistochemical data relies on a thorough understanding of the biological and technical factors that affect the detection of MMR proteins. In this review, we analyze the data from the published research studies, pointing out the various factors affecting immunohistochemical detection of MMR proteins and projecting the utility of immunohistochemistry in different clinical settings.

show abstract

Section: Technical Factorsmentioning

confidence: 98%

The utility of immunohistochemical detection of DNA mismatch repair gene proteins

2004

View full text Add to dashboard Cite

show abstract

“…The change in length of these tandem repeats is termed MSI and is often associated with defects in DNA repair genes (1,2). MSI is associated with 10% to 15% of sporadic colorectal carcinomas (3). Colon tumors harboring MSI more frequently present with proximal location, large tumor size, decreased likelihood of metastasis, less advanced stage at diagnosis, and better prognosis compared with microsatellite-stable (MSS) colon cancers (4,5).…”

Section: Introductionmentioning

confidence: 99%

5,10-Methylenetetrahydrofolate Reductase 677 and 1298 Polymorphisms, Folate Intake, and Microsatellite Instability in Colon Cancer

Eaton¹,

Sandler

Carethers

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene plays a critical role in folate metabolism. Studies on the association between MTHFR polymorphisms and length changes in short tandem repeat DNA sequences [microsatellite instability (MSI)] are inconsistent. Using data from colon cancer cases (n = 503) enrolled as part of an existing population-based case-control study, we investigated the association between MTHFR 677 and MTHFR 1298 polymorphisms and MSI. We also examined whether the association was modified by folate intake. Participants were case subjects enrolled as part of the North Carolina Colon Cancer Study. Consenting cases provided information about lifestyle and diet during in-home interviews as well as blood specimens and permission to obtain tumor blocks. DNA from normal and tumor tissue sections was used to determine microsatellite status (MSI). Tumors were classified as MSI if two or more microsatellite markers (BAT25, BAT26, D5S346, D2S123, and D17S250) had changes in the number of DNA sequence repeats compared with matched nontumor tissue. Tumors with one positive marker (MSIlow) or no positive markers (microsatellite stable) were grouped together as non-MSI tumors (microsatellite stable). MTHFR 677 and MTHFR 1298 genotypes were determined by real-time PCR using the 5V exonuclease (Taqman) assay.Logistic regression was used to calculate odds ratio (OR) and 95% confidence intervals (95% CI). MSI was more common in proximal tumors (OR, 3.8; 95% CI, 1.7-8.4) and in current smokers (OR, 4.0; 95% CI, 1.6-9.7). Compared with MTHFR 677 CC referent, MTHFR 677 CT/TT genotype was inversely associated with MSI among White cases (OR, 0.36; 95% CI, 0.16-0.81) but not significant among African Americans. Although not statistically significant, a similar inverse association was observed between MTHFR 677 CT/TT genotype and MSI among the entire case subjects (OR, 0.54; 95% CI, 0.26-1.10). Among those with adequate folate intake (>400 Mg total folate), we found strong inverse associations between combined MTHFR genotypes and MSI (677 CC + 1298 AC/CC, OR, 0.09; 95% CI, 0.01-0.59; 677 CT/TT + 1298 AA, OR, 0.13; 95% CI, 0.02-0.85) compared with the combined wild-type genotypes (677 CC + 1298 AA). This protective effect was not evident among those with low folate (<400 Mg total folate) intake. Our results suggest that MTHFR variant genotypes are associated with reduced risk of MSI tumors under conditions of adequate folate intake, although the data are imprecise due to small numbers. These results indicate that the relationship between MTHFR genotypes and MSI is influenced by folate status. (Cancer Epidemiol Biomarkers Prev 2005;14(8):2023 -9)

show abstract

“…The presence of intratumoral heterogeneity of hMLH1 expression in SCRCs has been demonstrated previously [23, 33]. Furthermore, Chapusot et al [33] extracted DNA from different areas defined by immunohistochemical analysis of hMLH1 (regions with expression or without expression) within tumors and showed that MSI occurs in regions without hMLH1 expression but not in those with such expression. Their study did not analyze hMLH1 promoter methylation, whereas we found that tumors with heterogeneous loss of hMLH1 expression were detected only in hMLH1 -methylation-positive SCRCs.…”

Section: Discussionmentioning

confidence: 99%

Microsatellite Instability Caused by <i>hMLH1</i> Promoter Methylation Increases with Tumor Progression in Right-Sided Sporadic Colorectal Cancer

Noda

Kato²,

Yoshikawa

et al. 2005

Oncology

View full text Add to dashboard Cite

Objective: A subset of sporadic colorectal cancers (SCRCs) exhibits microsatellite instability (MSI). Most MSI in SCRCs is caused by hMLH1 inactivation due to promoter methylation. However, the role of MSI in the progression of SCRCs remains unclear. Methods: Thirty-two intramucosal cancers and 63 cancers with submucosal invasion were assigned to group 1 (early-stage cancer), and 30 Dukes’ B and 26 Dukes’ C cancers to group 2 (advanced-stage cancer). hMLH1 promoter methylation status was determined by methylation-specific PCR. MSI was determined using five markers. hMLH1 expression was determined immunohistochemically. Results: MSI was found in 1 of 95 (1.1%) tumors in group 1, compared with 4 of 56 (7.1%) tumors in group 2. In right-sided tumors, the overall frequency of hMLH1-methylation-positive tumors in group 1 was not significantly different from that in group 2 (17 of 43, 39.5%, vs. 9 of 23, 39.1%). In right-sided tumors with hMLH1 promoter methylation, the frequency of MSI-positive tumors in group 1 was significantly lower than that in group 2 (1 of 17, 5.9%, vs. 4 of 9, 44.4%, p = 0.0081). Conclusion: The frequency of MSI caused by hMLH1 promoter methylation increases with tumor progression in right-sided SCRCs.

show abstract

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas

Cited by 53 publications

References 20 publications

The utility of immunohistochemical detection of DNA mismatch repair gene proteins

The utility of immunohistochemical detection of DNA mismatch repair gene proteins

5,10-Methylenetetrahydrofolate Reductase 677 and 1298 Polymorphisms, Folate Intake, and Microsatellite Instability in Colon Cancer

Microsatellite Instability Caused by <i>hMLH1</i> Promoter Methylation Increases with Tumor Progression in Right-Sided Sporadic Colorectal Cancer

Contact Info

Product

Resources

About