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

Steinbakk, Anita; Malpica, Anaís; Slewa, Aida; Gudlaugsson, Einar; Janssen, Emiel A. M.; Arends, Mark; Kruse, Arnold‐Jan; Yu, Yinhua; Feng, Weiwei; Baak, Jan P. A.

doi:10.1007/s13402-011-0040-x

Cited by 11 publications

(6 citation statements)

References 39 publications

(64 reference statements)

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“…There have been reports indicating that MSI is a good prognostic factor in colorectal cancer and that MMR status does not contribute to prognosis in colorectal cancer [ 47 , 48 , 49 ]. There are many reports that there is no significant difference in survival rate between the MSI and MSS groups in endometrial cancer [ 50 , 51 , 52 , 53 ]. Taken together with the current results, the effect of MSI status on prognosis remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer

et al. 2017

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In recent years, it has become evident that tumor cells have immune escape mechanisms, and immune checkpoint inhibitor therapy (anti-PD-1/PD-L1 antibody) has shown benefit in various cancers. In endometrial tumors with microsatellite-instability (MSI), somatic mutations have the potential to encode ‘’non-self’’ immunogenic antigens, and lymphocytes have been shown to infiltrate the tumor. Therefore, immune checkpoint inhibitor therapy might be effective in endometrial cancers with MSI. Expression of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), the presence of tumor-infiltrating lymphocytes (CD8+), and PD-1/PD-L1 expression were assessed by immunohistochemistry in 149 patients with endometrial cancer. We examined whether tumors with MSI had an enhanced immune microenvironment and whether MSI could be a predictor of the therapeutic effect of PD-1/PD-L1 immunotherapy in endometrial cancer. Loss of MMR protein expression was identified in 42 (28.2%) of 149 patients (MSI group) with endometrial cancer. There was no significant relationship between MSI status and age (p = 0.193), histological grade (p = 0.097), FIGO stage (p = 0.508), pelvic lymph node metastasis (p = 0.139), or depth of myometrial invasion (p = 0.494). However, the presence of tumor-infiltrating lymphocytes (CD8+) and PD-L1/PD-1 expression were significantly higher in the MSI group compared to the microsatellite-stable group (p = 0.002, p = 0.001, and p = 0.008, respectively). These results suggest that immune checkpoint inhibitors (anti-PD-1/PD-L1 antibody) could be effective in endometrial cancers with MSI. The presence of MSI may be a biomarker for good response to PD-1/PD-L1 immunotherapy in endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer

et al. 2017

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“…Although dMMR has been associated with a better prognosis in CRC, its prognostic significance in EC is unclear . Whereas many studies have reported worse survival and/or shorter disease‐free survival among patients dMMR or microsatellite instability (MSI), other studies have demonstrated improved survival or no association . A recent meta‐analysis also demonstrated no association between MMR status and OS or RFS .…”

Section: Discussionmentioning

confidence: 99%

Mismatch repair deficiency identifies patients with high‐intermediate–risk (HIR) endometrioid endometrial cancer at the highest risk of recurrence: A prognostic biomarker

Backes

Haag

Cosgrove

et al. 2018

Cancer

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Background The objective of this study was to assess the correlation between mismatch repair (MMR) status, disease recurrence patterns, and recurrence‐free survival (RFS) in patients with high‐intermediate–risk (HIR) endometrioid endometrial cancer (EEC). Methods A single‐institution chart review for consecutive patients who were diagnosed with ECC between 2007 and 2016 was undertaken. Tumor MMR status was determined for all patients based on reported findings for mutL homolog 1 (MLH1), postmeiotic segregation (PMS2), mutS homolog 2 (MSH2), and MSH6 immunohistochemistry; and defective MMR (dMMR) status was defined as the lack of expression of at least 1 of these proteins. Patients were classified with HIR EEC according to criteria used for Gynecologic Oncology Group study 249. The factors associated with recurrence were assessed by logistic regression. RFS and associated factors were assessed by Kaplan‐Meier survival analysis and Cox proportional‐hazards models. Results In total, 197 patients who had HIR EEC (64 with dMMR and 133 with intact MMR [iMMR]) were identified, of whom 32 (16.2%) developed recurrent disease. The median follow‐up was 54 months. The recurrence rate for women who had dMMR was 28% compared with 10.5% for those who had iMMR (P = .002), independent of the type of adjuvant therapy they received. The increase in distant recurrences among patients who had dMMR was even more pronounced (14.1% vs 3%; P = .003). The estimated 5‐year RFS was 66% for women who had dMMR compared with 89% for those who had iMMR (P = .001). Excluding isolated vaginal recurrences, the difference in 5‐year RFS was 73.5% versus 95%, respectively (P = .0004). Conclusions Patients who had HIR EEC with dMMR had increased rates of recurrence and decreased RFS compared with those who had HIR EEC with iMMR, despite the receipt of similar adjuvant treatment. The current findings highlight the need for alternative treatment options and the importance of MMR status as a biomarker for patients with HIR EEC.

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“…But in 2009, Bilbao, at al. reported that MSI is related to vascular invasion (p = 0.009) and advanced stage (p = 0.04) [8]. It is also noted that MSI has an independent predictive value for DFS and local DFS in early stage (p = 0.044), suggesting that MSI may have a predictive role in radiotherapy response in this group [6].…”

Section: Discussionmentioning

confidence: 82%

“…However, neither OS nor DFS was effected by MSI status in early stage (p = 0.284, p = 0.243). reported that MSI has prognostic value only for stage 1 cases in endometrioid adenocarcinoma (p = 0.005) [8].…”

Section: Discussionmentioning

confidence: 99%

Research of Prognostic Role of MSI in Endometrioid Adenocarcinoma Cases That Received Postoperative Radiotherapy

Kadriye¹,

Demiroz²,

Serdar³

et al. 2019

Int J Cancer Clin Res

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In this study, the relationship between MSI (microsatellite instability) and the parameters such as age, stage, histologic grade, recurrence, overall survival (OS), disease free survival (DFS) were investigated in 99 endometrioid adenocancer patients. Our aim is to find out the whether there is a prognostic value of MSI in endometrium adenocarcinoma. In MSI analysis, by employing the Promega MSI Analysis System. 'IBM SPSS v.20' was used for statistical analysis. MSI was identified in 19.1% of patients. There was no statistically significant effect of MSI on OS (p = 0.404) or on DFS (p = 0.407). MSI was found associated with younger age (p = 0.032), lymph node involvement (p = 0.012) and advanced stage (p = 0.014).

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

Cited by 11 publications

References 39 publications

Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer

Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer

Mismatch repair deficiency identifies patients with high‐intermediate–risk (HIR) endometrioid endometrial cancer at the highest risk of recurrence: A prognostic biomarker

Research of Prognostic Role of MSI in Endometrioid Adenocarcinoma Cases That Received Postoperative Radiotherapy

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