Synopsis

Keywords: Pelvis, Cancer

Microsatellite instability (MSI), which results from the failure of mismatch repair (MMR) proteins to fix a DNA replication error, causes insertions, mismatches, or deletions during the DNA replication process, thus having an essential role in maintaining the stability of the genome and regulating gene expression

Synopsis

Microsatellite instability (MSI), which results from the failure of mismatch repair (MMR) proteins to fix a DNA replication error, causes insertions, mismatches, or deletions during the DNA replication process, thus having an essential role in maintaining the stability of the genome and regulating gene expression

Summary of main Findings

This study showed that the MK and Ka values of the MSI group were higher than those of the MSS group (P<0.05), and the MD and Dr values were lower than those of the MSS group

Introduction and Purpose

Microsatellite instability (MSI), which results from the failure of mismatch repair (MMR) proteins to fix a DNA replication error, causes insertions, mismatches, or deletions during the DNA replication process, thus having an essential role in maintaining the stability of the genome and regulating gene expression (1-3). MSI is considered as one of the pathogenesis of endometrial carcinoma (EC) (4). The use of magnetic resonance imaging (MRI) related techniques can be used to predict the MSI status of EC before surgery. The diffusion kurtosis imaging (DKI) sequence is an extension of the diffusion-weighted imaging (DWI) and the diffusion tensor imaging (DTI) sequence. This study aimed to explore the value of multiple quantitative parameters of DKI sequence in predicting MSI status of EC to provide new ideas for non-invasive preoperative diagnosis in predicting MSI status and expanding the application of DKI sequence for uterine diseases.

Materials and Methods

38 patients were collected in the study, including 12 in the MSI group and 26 in the MSS group. MR examinations included T1W, T2W and DKI were performed within two weeks before surgery. The specific scanning parameters are shown in Table 1. Referring to the T2WI images, the largest section of the lesion and it's upper and lower 1-2 levels were selected. The regions of interest (ROIs) were manually drawn in the tumor parenchymal area, avoiding the areas of necrosis, hemorrhage, and cystic degeneration, and appropriately avoiding the lesion's edge, after which the average value was taken. The quantitative parameters included mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr), and fractional anisotropy (FA), fractional anisotropy of kurtosis (FAk), mean diffusivity (MD), axial diffusivity (Da), and radial diffusivity (Dr) (Figure 1). The independent-sample t-test (normal distribution) or Mann-Whitney U test (skew distribution) was used to compare the differences between the parameter values of the two groups. The receiver operator characteristic (ROC) curve was used to analyze the diagnostic efficiency and the best diagnostic threshold of different parameters. The area under curve (AUC) was calculated, as well as the corresponding sensitivity and specificity.

Results

Patient Characteristics Patients in the MSI group were 47-82 years old, with an average of (64.1±9.8) years old; there were 2 premenopausal cases and 10 post-menopausal cases. Patients in the MSS group were 35-78 years old, with an average of (56.7±12.8) years old; there were 12 cases before menopause and 14 cases after menopause. Agreement on Imaging Parameters among the Three Observers The consistency test results of the parameters between the two groups by the two observers are shown in Table 2, and the consistency of the data in each group was very good (ICC>0.75). Comparison of DKI parameters between the two groups The parameter values and results comparison between the MSI group and the MSS group are shown in Table 3. The MD and Dr values of the MSI group were smaller than those in the MSS group, while the MK and Ka values were greater than those in the MSS group. The differences were statistically significant. Efficacy of various parameters to diagnose MSI of EC and their comparison results The parameters of the DKI sequence to identify the AUC of the two groups, the threshold, sensitivity and specificity of predicting MSI status of EC are shown in Table 4; the ROC curve is presented in Figure 2.

Discussion and Conclusion

MSI is closely related to the occurrence of Lynch syndrome (LS). Patients with LS have a significantly increased risk of developing colorectal cancer, ovarian cancer, and EC. EC usually occurs before other tumors and is considered the "sentinel Cancer" of LS patients. (5,6). Our results showed that the MK and Ka values of EC in the MSI group (1.074±0.162, 1.253±0.229) were higher than those in the MSS group (0.956 (0.889,1.002), 1.048±0.211). MD and Dr values in the MSI group were lower than those of the MSS group. As the activity and ability of tumor cell proliferation of MSI-related EC are higher than that of MSS-related EC, and there are more lymphocytes and other substances infiltrating tumor tissue, it is speculated that the tumor cells of MSI-related EC are more compactly arranged, the extracellular space is smaller, and the degree of water molecule diffusion is more restricted. In conclusion, as non-enhanced functional imaging of MR, DKI can provide multiple quantitative parameters for non-invasive prediction of MSI status of EC, such as MK, Ka, MD, and Dr, and it has certain clinical application value.

Acknowledgements

no acknowledgements

References

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