Microsatellite instability in endometrioid endometrial carcinoma: correlation with clinically relevant pathologic variables

Honoré, Louis H.; Hanson, John M.; Andrew, Susan E.

doi:10.1111/j.1525-1438.2006.00535.x

Cited by 32 publications

(26 citation statements)

References 58 publications

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“…MSI-L and MSI-H were found in 11% and 16% of the cancers analyzed (totalling 27%). Of 17 previous studies on MSI in endometrial cancer, the prevalence of MSI widely varied from 9% to 45% [1,4,5,7,10,12,16,17,19,25,26,28,29,32,33,42,44] (Table 1). The table also illustrates the enormous variation in the numbers of patients, stages, histotypes and molecular techniques used in the different studies.…”

Section: Discussionmentioning

confidence: 99%

“…Increased understanding of the molecular biology in endometrial carcinogenesis has revealed several promising prognostic and predictive biomarkers, such as microsatellite instability (MSI), a characteristic finding in cancers deficient in DNA mis-match repair (MMR), seen in 9-45% of sporadic endometrial cancers (Table 1) [1,[4][5][6][7]10,12,16,17,19,25,26,28,29,32,33,42,44]. In contrast to Hereditary NonPolyposis Colorectal Cancer (HNPCC) or Lynch syndrome, which is an autosomal dominant condition involving germline MMR gene mutation, sporadic en- [15].…”

Section: Introductionmentioning

confidence: 99%

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High frequency microsatellite instability has a prognostic value in endometrial endometrioid adenocarcinoma, but only in FIGO stage 1 cases

et al. 2011

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Abstract. Objectives:To analyze the prognostic value of microsatellite instability (MSI) in a population-based study of FIGO stage 1-4 endometrial endometrioid adenocarcinomas.Study design: Survival analysis in 273 patients of MSI status and clinico-pathologic features. Using a highly sensitive pentaplex polymerase chain reaction to establish MSI status, cases were divided into microsatellite stable (MSS), MSI-low (MSI-L, 1 marker positive) and MSI-high (MSI-H, 2-5 markers positive).Results: After 61 months median follow-up (1-209), 34 (12.5%) of the patients developed metastases but only 6.4% of the FIGO 1. MSI (especially as MSI-H vs. MSS/MSI-Lcombined) was prognostic in FIGO 1 but not in FIGO 2-4. The 5 and 10 year recurrence-free survival rates were 98% and 95% in the MSS/MSI-L vs. 85% and 73% in the MSI-H patients (p = 0.005).Conclusions: MSI-H status assessed by pentaplex polymerase chain reaction is an indicator of poor prognosis in FIGO 1, but not in FIGO 2-4 endometrial endometrioid adenocarcinomas.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High frequency microsatellite instability has a prognostic value in endometrial endometrioid adenocarcinoma, but only in FIGO stage 1 cases

et al. 2011

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“…Two studies from 2006 in a relatively large-scale cohort of EMC patients showed significant associations between tumor MSI-H and advanced tumor stage, myometrial invasion, and improved survival. 24,25 However, a later study, in 2014, showed no associations of MSI status with survival, tumor grade, tumor stage, or histologic examination findings in 109 patients. 26 In our study, a correlation between International Federation of Gynecology and Obstetrics grade and MSI status was observed.…”

Section: Discussionmentioning

confidence: 99%

Differences in Microsatellite Instability Profiles between Endometrioid and Colorectal Cancers

Wang

Shi

Eisenberg

et al. 2017

The Journal of Molecular Diagnostics

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The ASCP designates this journal-based CME activity ("JMD 2017 CME Program in Molecular Diagnostics") for a maximum of 36 AMA PRA Category 1 Credit(s)ä. Physicians should claim only credit commensurate with the extent of their participation in the activity. CME Disclosures: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Colorectal (CRCs) and endometrioid (EMCs) cancers in patients with Lynch syndrome exhibit microsatellite instability (MSI) detected by PCR or immunohistochemistry (IHC). While both assays are equally sensitive for CRCs, some suggest that PCR has a higher false-negative rate than IHC in EMCs. We assessed the MSI profiles of 91 EMC and 311 CRC specimens using five mononucleotide repeat markers: BAT25, BAT26, NR21, NR24, and MONO27. EMCs with high MSI (MSI-H) showed a mean left shift of 3 nucleotides (nt), which was significantly different from 6 nt in CRCs. A shift of 1 nt was observed in multiple markers in 76% of MSI-H EMCs, whereas only 12% of MSI-H CRCs displayed a 1-nt shift in one of five markers. IHC against four mismatch repair proteins was performed in 78 EMCs. Loss of staining in one or more proteins was detected in 18 of 19 tumors that were MSI-H by PCR. When EMC tumor cell burden was diluted to <30%, MSI-H was no longer observed in two of three EMCs with a mean nucleotide shift of 1 nt. These results indicate that EMC and CRC MSI profiles are different and that caution should be exercised when interpreting the results, as subtle, 1-nt changes may be missed. These findings provide a potential cause of previously reported discordant MSI and IHC results in EMCs. Lynch syndrome (LS) (Online Mendelian Inheritance in Man no. 120435), also referred as hereditary nonpolyposis colorectal cancer, is an autosomal dominant disorder with a relatively common disease prevalence of 1 in 440.1,2 About 2% to 3% of colorectal cancers (CRCs) and 1% to 2% of endometrioid cancers (EMCs; including endometrial cancer and endometrioid cancer of the ovary) are due to LS.3 LS is a heterogeneous disorder exhibiting reduced penetrance, differences in age of onset, and variability in expression.In LS patients, the lifetime risks are 50% to 70% for CRC and 40% to 60% for EMC in women, and the overall risk for other associated tumors is increased. 4 LS is caused by germline mutations in one of four mismatch repair (MMR) genes or by a deletion in the EPCAM locus affecting the adjacent MMR gene.5 These germline mutations result in defective MMR machinery that leads to microsatellite instability (MSI) throughout the genome and gives rise to tumors. Both Lynch-related and sporadic cancers can manifest MSI. MSI tumors are associated with a better prognosis yet a poor response to adjuvant 5-fluorouracil based chemotherapy.

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“…In the case of endometrial carcinoma, however, there have been only limited pathologic studies [5,[11][12][13]. Although certain pathologic parameters, such as histologic type, grade, extent of myometrial invasion, and lymphovascular invasion, have been suggested as related to the MSI phenotype, the data are relatively scant and the significance of such parameters in detecting MSI tumors remains to be defined.…”

Section: Introductionmentioning

confidence: 96%

Routinely assessed morphological features correlate with microsatellite instability status in endometrial cancer

et al. 2008

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Microsatellite instability in endometrioid endometrial carcinoma: correlation with clinically relevant pathologic variables

Cited by 32 publications

References 58 publications

High frequency microsatellite instability has a prognostic value in endometrial endometrioid adenocarcinoma, but only in FIGO stage 1 cases

High frequency microsatellite instability has a prognostic value in endometrial endometrioid adenocarcinoma, but only in FIGO stage 1 cases

Differences in Microsatellite Instability Profiles between Endometrioid and Colorectal Cancers

Routinely assessed morphological features correlate with microsatellite instability status in endometrial cancer

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