Dataset Information

Instability of Non-Standard Microsatellites in Relation to Prognosis in Metastatic Colorectal Cancer Patients.

ABSTRACT: Very few data are reported in the literature on the association between elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) and prognosis in advanced colorectal cancer. Moreover, there is no information available in relation to the response to antiangiogenic treatment. We analyzed EMAST and vascular endothelial growth factor-B (VEGF-B) microsatellite status, together with standard microsatellite instability (MSI), in relation to prognosis in 141 patients with metastatic colorectal cancer (mCRC) treated with chemotherapy (CT) alone (n = 51) or chemotherapy with bevacizumab (B) (CT + B; n = 90). High MSI (MSI-H) was detected in 3% of patients and was associated with progression-free survival (PFS; p = 0.005) and overall survival (OS; p < 0.0001). A total of 8% of cases showed EMAST instability, which was associated with worse PFS (p = 0.0006) and OS (p < 0.0001) in patients treated with CT + B. A total of 24.2% of patients showed VEGF-B instability associated with poorer outcome in (p = 0.005) in the CT arm. In conclusion, our analysis indicated that EMAST instability is associated with worse prognosis, particularly evident in patients receiving CT + B.

SUBMITTER: Pirini F

PROVIDER: S-EPMC7279028 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Instability of Non-Standard Microsatellites in Relation to Prognosis in Metastatic Colorectal Cancer Patients.

Pirini Francesca F Pasini Luigi L Tedaldi Gianluca G Scarpi Emanuela E Marisi Giorgia G Molinari Chiara C Calistri Daniele D Passardi Alessandro A Ulivi Paola P

International journal of molecular sciences 20200516 10

Very few data are reported in the literature on the association between elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) and prognosis in advanced colorectal cancer. Moreover, there is no information available in relation to the response to antiangiogenic treatment. We analyzed EMAST and vascular endothelial growth factor-B (VEGF-B) microsatellite status, together with standard microsatellite instability (MSI), in relation to prognosis in 141 patients with metastat ...[more]

PMID: 32429465

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Project description:PurposeA Topoisomerase 1 (Top1) poison is frequently included in the treatment regimens for metastatic colorectal cancer (mCRC). However, no predictive biomarkers for Top1 poisons are available. We here report a study on the TOP1 gene copy number in CRC patients and its association with patient prognosis and tumor cell proliferation.Experimental designThe study included TOP1 and CEN-20 fluorescence in situ hybridization (FISH) analyses on formalin fixed paraffin embedded (FFPE) tissue sections from 154 stage III CRC chemonaïve patients. The frequencies of aberration in the TOP1 gene copy number, the CEN-20 copy number and the TOP1/CEN-20 ratio were analyzed and associated with overall survival (OS), time to recurrence (TTR) and in a subgroup analysis of rectal cancer patients only with time to local recurrence (LR in RC). Moreover, the TOP1 and CEN-20 copy numbers were correlated with the tumor Ki67 proliferation index.Results35.7% of the tumors had an increased TOP1 copy number above 4n gene copies per cell and 28.6% and 9.7% had a TOP1/CEN-20 ratio ?1.5 or ?2.0, respectively. The TOP1 copy number and the TOP1/CEN-20 ratios were separately added into multivariate analyses as continuous variables, in which also age, gender, primary tumor location and Ki67 status were added as covariates. In contrast to the TOP1/CEN-20 ratio, the TOP1 copy number was significantly associated with OS (HR: 0.62; 95% CI: 0.42-0.90; p = 0.01). Neither the TOP1 copy number nor the ratio was significantly associated with TTR and only the TOP1/CEN-20 ratio was significantly associated with LR in RC (HR: 0.25; 95% CI: 0.08-0.83; p = 0.02). No significant correlation was found between the TOP1 copy number and proliferation, while a weak and inverse correlation between the CEN-20 copy number and proliferation was observed.ConclusionsThis study showed that increased TOP1 gene copy numbers are frequent findings in cancer cells in stage III CRC tumors but unrelated to the proliferative status of the tumors. The association with prognosis is important to consider when planning and analyzing future studies investigating TOP1 as a potential predictive biomarker for Top1 poisons.

Dataset Information

Instability of Non-Standard Microsatellites in Relation to Prognosis in Metastatic Colorectal Cancer Patients.

Publications

Instability of Non-Standard Microsatellites in Relation to Prognosis in Metastatic Colorectal Cancer Patients.

Similar Datasets

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