A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability

Cancer ◽  
2021 ◽  
Author(s):  
Stefania Bellone ◽  
Dana M. Roque ◽  
Eric R. Siegel ◽  
Natalia Buza ◽  
Pei Hui ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Phase 2 ◽  
Endometrial Cancers

scholarly journals Cross-platform Data Analysis Reveals a Generic Gene Expression Signature for Microsatellite Instability in Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Anna Pačínková ◽  
Vlad Popovici
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Colon Cancer ◽  
Microsatellite Instability ◽  
Gene Expression Signature ◽  
Data Sets ◽  
Rna Seq ◽  
Cancer Data ◽  
Expression Signature ◽  
Endometrial Cancers

The dysfunction of the DNA mismatch repair system results in microsatellite instability (MSI). MSI plays a central role in the development of multiple human cancers. In colon cancer, despite being associated with resistance to 5-fluorouracil treatment, MSI is a favourable prognostic marker. In gastric and endometrial cancers, its prognostic value is not so well established. Nevertheless, recognising the MSI tumours may be important for predicting the therapeutic effect of immune checkpoint inhibitors. Several gene expression signatures were trained on microarray data sets to understand the regulatory mechanisms underlying microsatellite instability in colorectal cancer. A wealth of expression data already exists in the form of microarray data sets. However, the RNA-seq has become a routine for transcriptome analysis. A new MSI gene expression signature presented here is the first to be valid across two different platforms, microarrays and RNA-seq. In the case of colon cancer, its estimated performance was (i) AUC = 0.94, 95% CI = (0.90 – 0.97) on RNA-seq and (ii) AUC = 0.95, 95% CI = (0.92 – 0.97) on microarray. The 25-gene expression signature was also validated in two independent microarray colon cancer data sets. Despite being derived from colorectal cancer, the signature maintained good performance on RNA-seq and microarray gastric cancer data sets (AUC = 0.90, 95% CI = (0.85 – 0.94) and AUC = 0.83, 95% CI = (0.69 – 0.97), respectively). Furthermore, this classifier retained high concordance even when classifying RNA-seq endometrial cancers (AUC = 0.71, 95% CI = (0.62 – 0.81). These results indicate that the new signature was able to remove the platform-specific differences while preserving the underlying biological differences between MSI/MSS phenotypes in colon cancer samples.

Increased risk for abnormalities on perioperative colon screening in patients with microsatellite instability–positive endometrial carcinoma

2006 ◽  
Vol 16 (6) ◽  
pp. 1980-1986 ◽  
Author(s):  
B. M. Buttin ◽  
M. A. Powell ◽  
P. J. Goodfellow ◽  
S. N. Lewin ◽  
R. K. Gibb ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Microsatellite Instability ◽  
Medical Records ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Molecular Stratification ◽  
Colon Cancers ◽  
Increased Risk ◽  
Primary Colon ◽  
Endometrial Cancers

Microsatellite instability (MSI) is a feature of certain hereditary and sporadic endometrial and colon cancers. We set out to determine whether molecular stratification of endometrial cancers based on tumor MSI status could help identify patients at increased risk for abnormalities found on perioperative colon screening. From a prospectively accrued series of 413 patients, medical records were reviewed from 94 patients with MSI positive (MSI+) and 94 patients with MSI negative (MSI−) endometrial cancers, matched by year of diagnosis. We reviewed clinicopathologic data and results of perioperative colon screening. Differences were analyzed using Fisher exact test and logistic regression analysis. There were no significant clinicopathologic differences between the two cohorts. Sixty-five percent of patients in each group underwent perioperative colon screening. However, patients with MSI+ cancers had a twofold increase in the frequency of colonic abnormalities (30% versus 14.8%, P= 0.044) over those with MSI− cancers. Furthermore, the only primary colon cancers (N= 2) were found in women with MSI+ endometrial cancers that were unmethylated at the MLH1 promoter. Our data suggest that patients with MSI+ endometrial cancers are at increased risk for abnormalities on perioperative colon screening. Those with MSI+MLH1 unmethylated cancers appear to be at highest risk.

Results of a phase 2 trial of ribociclib and letrozole in patients with either relapsed estrogen receptor (ER)-positive ovarian cancers or relapsed ER-positive endometrial cancers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5510-5510 ◽  
Author(s):  
Gerardo Colon-Otero ◽  
S. John Weroha ◽  
Valentina Zanfagnin ◽  
Nathan R. Foster ◽  
Erik Asmus ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Estrogen Receptor ◽  
Low Grade ◽  
Favorable Result ◽  
High Grade ◽  
Phase 2 ◽  
Ct Guided ◽  
Er Positive ◽  
Endometrial Cancers ◽  
Tumor Biopsies

5510 Background: Single agent aromatase inhibitor (AI) therapy is associated with limited clinical activity in ovarian cancer (OC) and endometrial cancers (EC). AI therapy was associated with a progression free survival (PFS) at 12 weeks of only 20% in relapsed OC (Bowman et al, 2002) and a median PFS of 1 month in relapsed EC (Rose et al, 2000). In Estrogen Receptor (ER) positive metastatic breast cancer, clinical studies had shown a significant prolongation of PFS with the addition of the cyclin kinase 4/6 inhibitor ribociclib to AI (Hortobagyi et al, 2016). Here, we report the results of a phase 2 clinical trial of the combination of ribociclib and letrozole in patients with relapsed ER positive OC or EC. Objectives: Primary endpoint was the proportion of patients with relapsed ER positive OC or EC alive and progression-free after 12 weeks of therapy (PFS12) with the combination of ribociclib given at a dose of 400 mg orally daily and letrozole 2.5 mg orally daily. A PFS of 45% was considered a favorable result based on the data referenced above from Bowman et al. Methods: Eligibility criteria included patients with relapsed ER positive OC or EC, with measurable disease, not previously treated with ribociclib or AIs. Xenografts were created from CT guided tumor biopsies at baseline to assess feasibility. Results: A total of 40 patients were enrolled (20 with OC and 20 with EC) ) with a median age of 61 years (range: 30-82) and 64.5 (range: 52-75) in the OC and EC groups respectively. Among the OC patients, 17 had high grade serous carcinomas and 3 had low grade serous carcinomas. 11 EC patients had endometrioid cancers (3 with grade 1 tumors) and 9 had high grade serous tumors. Ten out of 20 OC patients and 11/20 EC patients were alive and progression-free at 12 weeks (PFS12 of 50 and 55%, respectively). The most common grade 3 or higher adverse events (occurring in at least 5 pts) were leukopenia (18%), lymphopenia (18%), neutropenia (13%), and fatigue (13%). 34 tumor biopsies were suitable for injection into mice and 44% engrafted. ER expression persisted through multiple passages in mice. Two of three EC PDX models exhibited improved PFS with letrozole/ribociclib compared to letrozole alone. Conclusions: The combination of ribociclib and letrozole is associated with a promising 50% and 55% PFS12 in patients with ER positive relapsed OC or EC respectively. Creation of xenograft tumor models from CT guided biopsies of OC and EC tumors was feasible. Clinical trial information: NCT02657928.

BAT-26 microsatellite instability does not correlate with the loss of hMLH1 and hMSH2 protein expression in sporadic endometrial cancers

2003 ◽  
Author(s):  
Roman Miturski ◽  
Michal Bogusiewicz ◽  
Rafal Tarkowski ◽  
Carmella Ciotta ◽  
Margherita Bignami ◽  
...  
Keyword(s):  
Protein Expression ◽  
Microsatellite Instability ◽  
Endometrial Cancers

Absence of PTEN Repeat Tract Mutation in Endometrial Cancers with Microsatellite Instability

2000 ◽  
Vol 79 (1) ◽  
pp. 101-106 ◽  
Author(s):  
David E Cohn ◽  
Jack B Basil ◽  
Anna R Venegoni ◽  
David G Mutch ◽  
Janet S Rader ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Repeat Tract ◽  
Endometrial Cancers

MLH1 Promoter Methylation and Gene Silencing is the Primary Cause of Microsatellite Instability in Sporadic Endometrial Cancers

1999 ◽  
Vol 8 (4) ◽  
pp. 661-666 ◽  
Author(s):  
S. B. Simpkins ◽  
T. Bocker ◽  
E. M. Swisher ◽  
D. G. Mutch ◽  
D. J. Gersell ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Microsatellite Instability ◽  
Promoter Methylation ◽  
Mlh1 Promoter ◽  
Endometrial Cancers
Sign in / Sign up

Export Citation Format

Share Document