Objective: The aim of this study was to establish criteria that would indicate whether fertility preservation therapy would likely be safe for patients aged 40 years or less with endometrioid endometrial cancer based on their DNA methylation profile. Methods: Forty-nine fresh-frozen tissue samples from patients with endometrial cancer from an initial cohort and 31 formalin-fixed paraffin-embedded tissue samples from a second cohort were subjected to genome-wide DNA methylation analysis using the Infinium MethylationEPIC BeadChip. Results: Epigenomic clustering of early-onset endometrial cancer was correlated with the widely used recurrence risk classification. Genes showing differences in DNA methylation levels between the low-recurrence-risk category and intermediate- and high-risk categories were accumulated in pathways related to fibroblast growth factor and nuclear factor-κB signaling. DNA hypomethylation and overexpression of ZBTB38 were frequently observed in the low-risk category. Eight hundred thirty-one marker CpG probes showed area under the curve values of >0.7 on the receiver operating characteristic curve for discrimination of patients belonging to the low-risk category. By combining marker CpG sites, seven panels for placing patients into the low-risk category with 91.3% or more sensitivity and specificity in both the initial and second cohorts were established. Conclusions DNA methylation diagnostics criteria using up to 6 of 8 CpG sites for LPP, FOXO1, RNF4, EXOC6B, CCPG1, RREB1 and ZBTB38 may be applicable to recurrence risk estimation for patients aged 40 years or less with endometrial cancer, regardless of tumor cell content, even if formalin-fixed paraffin-embedded biopsy or curettage materials are used.

We report a case of burning mouth syndrome (BMS) in a woman in her 70s whose pain was relieved by goshajinkigan alone. Five years ago, she became aware of tongue pain when she was under emotional stress. We diagnosed it as BMS. Since she had been taking antidepressants for depression for a long time and was more bothered by symptoms of kidney deficiency, such as back pain and numbness in the lower limbs, than tongue pain, we first prescribed goshajinkigan to improve her general condition. After that, not only her kidney deficiency but her BMS was relieved. The patient is currently under follow-up, but there is no tendency to relapse BMS. We presume that the correction of the patient’s general condition by Kampo medicine would lead to the improvement of her BMS.