Multipopulation Analysis of Polymorphisms in Five Mononucleotide Repeats Used to Determine the Microsatellite Instability Status of Human Tumors

Buhard, Olivier; Cattaneo, Francesca; Wong, Yick Fu; Yim, So Fan; Friedman, Eitan; Fléjou, Jean‐François; Duval, Alex; Hamelin, Richard

doi:10.1200/jco.2005.02.7227

Cited by 214 publications

(217 citation statements)

References 21 publications

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“…MSI analysis was performed with 5 markers ( Table 1) that have been established as quasimonomorphic and have a low risk for polymorphisms (and, thus, a low rate of false-positive detection of MSI) in the Caucasian population, as described previously. 20,21 These selected markers have a high sensitivity for MSI without the need for matching with patients' normal DNA, as reported by others. 22 Polymerase chain reaction (PCR) amplification was performed under standard conditions.…”

Section: Microsatellite Instability Analysismentioning

confidence: 71%

“…16,31 Also, the discrepancies in the reported survival results also reflect the heterogeneity of the populations studied; eg, unselected or institutional series of sporadic CRC, 14,32 hereditary cancer (hereditary nonpolyposis CRC) screening, 19 analysis of adjuvant chemotherapy trials, 15,17 site-and/or stage-specific analyses (ie, only colonic cancers, only stage II and/or III cancers), as well as in age-related, geographic, and ethnical differences. 20,33 It is also is worth noting that, in the current study, the majority of older patients (aged >75 years) were excluded from the systematic surveillance program and, as such, were not included in the current survival analysis. Table 4 for TNM stages (A).…”

Section: Discussionmentioning

confidence: 99%

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Microsatellite instability and DNA ploidy in colorectal cancer

Søreide

Slewa

Stokkeland

et al. 2009

Cancer

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BACKGROUND:Appropriate stratification tools for targeted surveillance after resection for colorectal cancer (CRC) are lacking. The objective of the current study was to investigate the effect of microsatellite instability (MSI) and DNA ploidy on surveillance after surgery.METHODS:The authors evaluated 186 consecutive, population‐based patients with stage I through III CRC who underwent surgery with curative intent and who entered a systematic surveillance program. MSI was analyzed with polymerase chain reaction for 5 known quasimonomorphic markers (BAT‐26, BAT‐25, NR‐21, NR‐24, and NR‐27), and DNA ploidy was analyzed with automated cytometry. Recurrence, recurrence‐free survival (RFS), and disease‐specific survival (DSS) were evaluated by univariate and multivariate statistical tests.RESULTS:Patients with MSI (20%) were significantly younger than patients without MSI (median age, 61 years vs 67 years; P = .016). Proximal location (adjusted odds ratio [AOR], 5.4; 95% confidence interval [95% CI], 2.1‐14.1 [P = .001]), large tumor size (≥5 cm: AOR, 3.5; 95% CI, 1.3–9.6 [P = .015]), and poor tumor differentiation (AOR, 6.6; 95% CI, 2–21.8 [P = .002]) were associated with MSI. MSI conveyed an increased risk for locoregional recurrence (OR, 2.9; 95% CI, 1.2–7 [P = .016]), with a trend toward a shorter time to recurrence (P = .060). Neither MSI status nor DNA ploidy predicted distant metastasis, RFS, or DSS. Lymph node status was the best predictor of distant spread (AOR, 3.9; 95% CI, 2–7.9 [P < .001]) and DSS (hazard ratio, 4.9; 95% CI, 2.6–9 [P < .001]).CONCLUSIONS:Patients who had microsatellite instable tumors were at increased risk for locoregional recurrence, whereas lymph node status was the best predictor of distant metastasis. Clinical surveillance and choice of modality (ie, endoscopy vs radiologic imaging) may be improved when patients are stratified according to these cancer features. Cancer 2009. © 2009 American Cancer Society.

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Section: Microsatellite Instability Analysismentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Microsatellite instability and DNA ploidy in colorectal cancer

Søreide

Slewa

Stokkeland

et al. 2009

Cancer

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“…25,26 Microsatellite instability was defined by the presence of instability affecting at least two markers. According to the French regulation, a written consent had systematically been obtained for germline mutation analyses of the DNA mismatch repair system, which have been performed for medical purposes.…”

Section: Assessment Of Microsatellite Instabilitymentioning

confidence: 99%

Tumor-infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frameshift mutations

et al. 2009

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Colorectal cancers with microsatellite instability are characterized by an important density of tumor-infiltrating lymphocytes and a good prognosis. Microsatellite instability results from the inactivation of the DNA mismatch repair system and induces secondary somatic frameshift mutations within target genes harboring repeat sequences in their coding frame. By disrupting the open reading frame, frameshift mutations can result in the appearance of potentially immunogenic neopeptides. To determine the frameshift mutations inducing a T-cell response during the development of a tumor with microsatellite instability, we studied in 61 colorectal cancer patients with microsatellite instability, using a fluorescent multiplex PCR comparative analysis, the relative frequency of frameshift mutations within 19 target genes and analyzed the correlation of these frameshift mutations with the density of CD3 þ tumor-infiltrating lymphocytes. The four most frequently mutated genes were ACVR2 (92%), TAF1B (84%), ASTE1/HT001 (80%) and TGFBR2 (77%). The vast majority (95%) of the tumors exhibited at least three frameshift mutations, and the number of frameshift mutations was associated with tumor progression (TNM stage, wall invasion and tumor diameter). Tumor-infiltrating lymphocyte density was associated with the overall number of frameshift mutations and with the presence of frameshift mutations within two target genes, namely ASTE1/HT001 and PTEN. These results strongly argue for the clinical relevance of immunotherapy of colorectal cancers with microsatellite instability.

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“…Microsatellite instability analysis was performed with five markers (BAT-26, BAT-25, NR-21, NR-24 and NR-27) known to be quasimonomorphic and with low risk for polymorphisms in the Caucasian population, as previously described. [15][16][17][18] The selected markers show a high sensitivity for microsatellite instability without the need for matching with patient's normal DNA. PCR amplification was performed under standard conditions.…”

Section: Microsatellite and Dna Ploidy Analysismentioning

confidence: 99%

Biomarkers and microsatellite instability analysis of curettings can predict the behavior of FIGO stage I endometrial endometrioid adenocarcinoma

et al. 2011

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The prognostic value of molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in endometrial cancer is conflicting, possibly due to the fact that different studies have used mixtures of histotypes, FIGO stages and different non-standardized non-automated methods. We have evaluated the prognostic value of classical prognostic factors, molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in a population-based cohort of FIGO stage I endometrial endometrioid adenocarcinomas. Curettings of 224 FIGO stage I endometrial endometrioid adenocarcinoma patients were reviewed. Clinical information, including follow-up, was obtained from the patients' charts. Microsatellite instability and morphometric mean shortest nuclear axis were obtained in whole tissue sections and molecular biomarkers using tissue microarrays. DNA ploidy was analyzed by image cytometry. Univariate (Kaplan-Meier method) and multivariate (Cox model) survival analysis was performed. With median follow-up of 66 months (1-209), 14 (6%) patients developed metastases. Age, microsatellite instability, molecular biomarkers (p16, p21, p27, p53 and survivin) and morphometric mean shortest nuclear axis had prognostic value. With multivariate analysis, combined survivin, p21 and microsatellite instability overshadowed all other variables. Patients in which any of these features had favorable values had an excellent prognosis, in contrast to those with either high survivin or low p21 (97 vs 78% survival, Po0.0001, hazard ratio ¼ 7.8). Combined high survivin and low p21 values and microsatellite instability high identified a small subgroup with an especially poor prognosis (survival rate 57%, P ¼ 0.01, hazard ratio ¼ 5.6). We conclude that low p21 and high survivin expression are poor prognosis indicators in FIGO stage I endometrial endometrioid adenocarcinoma, especially when high microsatellite instability occurs. Modern Pathology (2011Pathology ( ) 24, 1262Pathology ( -1271 doi:10.1038/modpathol.2011 published online 6 May 2011 Keywords: endometrial cancer; FIGO I; microsatellite instability; prognostic; p21; survivin Endometrial carcinoma is the most frequent gynecological cancer. The disease-related death rate in FIGO stage II-IV is high (20-80% and higher), while in the 'favorable' early stage FIGO I, the death rate ranges from 5 to 15%, 1,2 which has been stable for decades.3 This prompts the search of other prognostic indicators to enable a more accurate triaging

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Multipopulation Analysis of Polymorphisms in Five Mononucleotide Repeats Used to Determine the Microsatellite Instability Status of Human Tumors

Abstract: We demonstrated that tumor MSI status can be determined using the pentaplex reaction for all human populations without the need for matching normal DNA.

Cited by 214 publications

References 21 publications

Microsatellite instability and DNA ploidy in colorectal cancer

Microsatellite instability and DNA ploidy in colorectal cancer

Tumor-infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frameshift mutations

Biomarkers and microsatellite instability analysis of curettings can predict the behavior of FIGO stage I endometrial endometrioid adenocarcinoma

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