Microsatellite instability and ploidy status define three categories with distinctive prognostic impact in endometrioid endometrial cancer

Abstract

Microsatellite instability (MSI) and aneuploidy are inversely related phenomena. We tested whether ploidy status influences the clinical impact of MSI in endometrioid endometrial cancer (EEC). We analyzed 167 EECs for MSI and ploidy. Tumors were classified in three categories according to MSI and ploidy status. Associations with clinicopathological and molecular variables, survival, and treatment response were assessed.All MSI tumors (23%) were scored as diploid, and 14% of microsatellite stable (MSS) tumors presented aneuploidy. MSI tumors associated with older age at diagnosis, non-obesity, high histological grade, and advanced surgical stage. MSS-aneuploid tumors also associated with higher grade and advanced stage. In multivariate survival analysis MSI did not influence disease-free survival (DFS) or cancer-specific survival (CSS). However, when just diploid tumors were considered for the analysis, MSI significantly contributed to worse DFS and CSS, and the same was observed for aneuploidy when MSS tumors were analyzed alone. In diploid tumors, a differential response to postoperative radiotherapy (RT) was observed according to MSI, since it predicted poor DFS and CSS in the multivariate analysis.We conclude that ploidy status influences the clinical impact of MSI in EEC. Among diploid tumors those with MSI have poor clinical outcome and respond worse to RT.

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

“…Although dMMR has been associated with a better prognosis in CRC, its prognostic significance in EC is unclear. 21 Whereas many studies have reported worse survival and/or shorter disease-free survival among patients dMMR or microsatellite instability (MSI), 10,14,[22][23][24][25] other studies have demonstrated improved survival [26][27][28][29] or no association. [30][31][32][33] A recent meta-analysis also demonstrated no association between MMR status and OS or RFS.…”

LncRNA HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2

“…Further on, increased Microsatellite instability (MSI) and abnormal cell cycle protein play an important role in HOTAIR oncogenic event. Diploid tumors with Microsatellite instability (MSI) have poor clinical outcome and respond worse [ 45 , 46 ]. MMR defect seems to be related with sporadic-microsatellite instability (MSI) and Cell cycle proteins abnormal expression [ 47 ].…”

Proteomics of endometrial cancer diagnosis, treatment, and prognosis

“…PTEN, a tumor suppressor gene has been shown to be altered in up to 83% of endometrial adenocarcinomas and 55% in precancerous lesions [45]. Microsatellite instability (MSI) has been demonstrated in 20% of type I EC [46]. According to Bilbao et al both PTEN mutations and MSI represent early events in endometrial carcinogenesis [47].…”