Chromosomal abnormalities and microsatellite instability in sporadic endometrial cancer

Muresu, Rosella; Sini, Maria Cristina; Cossu, Antonio; Tore, Silvia; Baldinu, Paola; Manca, Antonella; Pisano, Marina; Loddo, C; Dessole, Salvatore; Pintus, Adriana; Tanda, Francesco; Palmieri, Giuseppe

doi:10.1016/s0959-8049(02)00152-1

Cited by 33 publications

(23 citation statements)

References 32 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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“…The incidence of MSI tumor was slightly lower in our study when compared with that from the literature using the same panel of 5 markers as recommended by the National Cancer Institute. MSI was reported in 25% to 32% of sporadic endometrial carcinoma unselected for age or family history (30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer

Chu

Liu

Tam

et al. 2015

International Journal of Gynecological Pathology

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The objective of this study was to identify the tumor characteristics associated with mismatch repair deficiency in young patients with endometrial carcinoma. Young patients (45 yr old or younger) with endometrial carcinoma treated by hysterectomy in our institution between July 2001 and June 2009 were identified. The clinical and pathologic data were obtained by review of clinical records. Among the 122 cases identified, paraffin sections were available in 67 cases for immunohistochemical staining and frozen tissue available in 62 cases for microsatellite instability (MSI) analysis. Both paraffin sections and frozen tissue were available in 36 cases. Among the 67 cases with immunohistochemical staining, 22 (32.8%) showed loss of expression of at least 1 mismatch repair protein. Defective MLH1 or MSH2 expression was associated with poor prognostic factors, including a higher incidence of pelvic lymph nodes metastasis (P=0.018) and higher stage (P=0.022) for MLH1, and an increased risk of lymphovascular permeation (P=0.015) for MSH2. On the contrary, defective MSH6 protein expression was associated with a lower incidence of high-grade tumors (P=0.04). Among the 62 cases with MSI analysis, 12 (19.4%) tumors were classified as microsatellite-high (MSI-H), whereas 2 (3.2%) were classified as microsatellite-low (MSI-L). There was no difference in the pathologic characteristics between MSI-stable and MSI-H tumor. We concluded that defective mismatch repair expression is important in young patients with endometrial carcinoma, with MSH6 protein being most commonly affected. The phenotype resulting from defective MSH6 expression was different from that caused by MLH1 or MSH2 loss.

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“…We found low-frequency microsatellite instability and high-frequency microsatellite instability in 11 and 16% of the cancers analyzed (in total 27%). The prevalence of microsatellite instability in endometrial cancer in the literature shows a wide variation ranging from 9 to 45%, [33][34][35][36][37][38][39][40][41][42][43][44][45][46] which again may be due to the use of different combinations of endometrial cancers regarding type and stage, but also differences in molecular techniques used (especially in the older studies when there was less consensus about the definition of markers used). Combining different types and stages is likely to blur the results, as type II tumors have a lower frequency of microsatellite instability than type I, more often show aneuploidy and more aggressive behavior.…”

Section: Microsatellite Instability In Endometrial Cancermentioning

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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Chromosomal abnormalities and microsatellite instability in sporadic endometrial cancer

Cited by 33 publications

References 32 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

The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer

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

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