Early risk-assessment of patients with nasopharyngeal carcinoma: the added prognostic value of MR-based radiomics.

OBJECTIVES: To assess the additive prognostic value of MR-based radiomics in predicting progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC) METHODS: Patients newly diagnosed with non-metastatic NPC between June 2006 and October 2019 were retrospectively included and randomly grouped into training and test cohorts (7:3 ratio). Radiomic features (n=213) were extracted from T2-weighted and contrast-enhanced T1-weighted MRI. The patients were staged according to the 8th edition of American Joint Committee on Cancer Staging Manual. The least absolute shrinkage and selection operator was used to select the relevant radiomic features. Univariate and multivariate Cox proportional hazards analyses were conducted for PFS, yielding three different survival models (clinical, stage, and radiomic). The integrated time-dependent area under the curve (iAUC) for PFS was calculated and compared among different combinations of survival models, and the analysis of variance was used to compare the survival models. The prognostic performance of all models was validated using a test set with integrated Brier scores. RESULTS: This study included 81 patients (training cohort=57; test cohort=24), and the mean PFS was 57.5 ± 43.6 months. In the training cohort, the prognostic performances of survival models improved significantly with the addition of radiomics to the clinical (iAUC, 0.72-0.80; p=0.04), stage (iAUC, 0.70-0.79; p=0.001), and combined models (iAUC, 0.76-0.81; p<0.001). In the test cohort, the radiomics and combined survival models were robustly validated for their ability to predict PFS. CONCLUSION: Integration of MR-based radiomic features with clinical and stage variables improved the prediction PFS in patients diagnosed with NPC.

O6-methylguanine-DNA-methyltransferase promoter methylation assessment by microdissection-assisted methylation-specific PCR and high resolution melting analysis in patients with glioblastomas.

We have determined O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status by methylation-specific polymerase chain reaction (MSP) in 22 paraffin-embedded specimens of glioblastoma multiforme. A MGMT methylation-specific high resolution melting (HRM) assay was performed to compare the methylation levels of the tumorous and non-tumorous portions of each sample, which were selectively collected using a microdissection technique. MGMT methylation was detected in 10 patients using MSP, while 8 patients had both methylated and unmethylated MGMT promoters. HRM assays showed that there was no difference in the level of methylation between tumorous and non-tumorous portions of each sample. In patients with MSP-positive tumors, the overall survival (median, 22 months) was longer as compared to those with MSP-negative tumors (median, 14 months). A correlation between the methylation status of the MGMT promoter and MGMT protein expression was observed in 12 samples. This study demonstrates that MGMT methylation is not restricted to glioblastoma cells. Additionally, methylation-specific HRM is a feasible approach that can be readily applied to the methylation analysis of MGMT. A further study will be needed to determine the dynamic change of MGMT methylation in the tumor environment.

Diagnostic use of nuclear beta-catenin expression for the assessment of endometrial stromal tumors.

Alterations in beta-catenin degradation cause it to accumulate to immunohistochemically detectable levels in the nuclei of tumor cells. Although it has been shown that nuclear beta-catenin immunostaining is useful for the diagnosis of some mesenchymal tumors, there is little known about beta-catenin expression in endometrial stromal tumors. In this study, nuclear beta-catenin immunoreactivity was evaluated in normal endometrium and endometrial mesenchymal tumors and then compared with that of CD10. The endometrial mesenchymal tumors evaluated included endometrial stromal nodules (n=2), low-grade endometrial stromal sarcomas (n=12), undifferentiated endometrial sarcomas (n=8) and uterine cellular leiomyomata (n=9). In addition, direct DNA sequencing of beta-catenin exon 3 was conducted in 15 endometrial stromal tumors. Normal endometrial stromal cells showed strong cytoplasmic reactivity for CD10 but no detectable reactivity for beta-catenin. Nuclear beta-catenin immunoreactivity was detected in 11 low-grade endometrial stromal sarcomas (92%) and 6 undifferentiated endometrial sarcomas (75%). Ten low-grade endometrial stromal sarcomas (83%) and six undifferentiated endometrial sarcomas (75%) were positive for CD10. Eight low-grade endometrial stromal sarcomas (67%) exhibited diffuse, strong nuclear immunoreactivity with beta-catenin, whereas only four cases (33%) expressed diffuse, strong immunoreactivity with CD10. All nine cases of uterine cellular leiomyomata were completely negative for both CD10 and beta-catenin. beta-catenin mutations were rare in endometrial stromal tumors. Taken together, these results indicate that nuclear beta-catenin immunostaining can serve as a sensitive immunohistochemical marker for the diagnosis of endometrial stromal tumors and is useful for differentiating low-grade endometrial stromal sarcomas from uterine cellular leiomyomata.