Oh RK, et al. Ann Surg Treat Res. 2020 Sep;99(3):153-160. https://doi.org/10.4174/astr.2020.99.3.153

Objectives. Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer.Methods. This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database.Results. Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension).Conclusion. We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.

Breast cancer patients with a human epidermal growth factor receptor 2 (HER2) enriched subtype are known to have higher rates of brain metastases (BM) than other patients. This study aimed to evaluate treatment options and survival outcomes. A total of 115 breast cancer brain metastases (BCBM) patients with nearly complete medical records were retrospectively analyzed. Additionally, 36 patients were HER2 enriched types according to histological subtypes. The BM was found by brain magnetic resonance imaging in patients who had neurologic symptoms or by regular screening. Age, breast tumor size, number of BM, histological subtypes, first treatment of breast cancer, estrogen receptor, and HER2 status, stage, local treatment of BM were analyzed. Median overall survival, 5-year survival were analyzed from the data. The median survival time after BM was 6 months, the mean survival time was 16.3 months, and the 5-year survival after BM was only 8.0%. Factors that significantly affect the survival of BCBM patients include histological subtype, number of BM, use of lapatinib in multivariate analysis. A total of 19 out of 36 HER2 enriched patients were treated with lapatinib or capecitabine. For the treatment of HER2 enriched patients, additional use of blood-brain barrier (BBB) crossing substances, as well as local treatment for BM, significantly improve the survival rate in the Kaplan-Meier method (P=0.001). A combination of local treatment modality for BCBM and the use of substances that cross the BBB for the HER2 enriched patient improved the survival rate.

Background/Objectives: Mammography remains central to breast cancer diagnosis, yet clinically meaningful uncertainty persists in women with dense breasts and in patients with very small lesions or indeterminate imaging findings. We evaluated whether circulating thioredoxin 1 (Trx1) could provide biological information that complements imaging-based assessment. Methods: This multicenter clinical validation study evaluated circulating Trx1 in 1901 serum samples across four predefined cohorts. Diagnostic performance was assessed using receiver operating characteristic (ROC) and precision–recall analyses, together with evaluation of integration with mammographic assessment and decision curve analysis (DCA). A predefined Trx1 cutoff established in prior clinical investigations was applied. Results: Circulating Trx1 concentrations were significantly elevated in breast cancer compared with controls (p < 0.001). Trx1 showed excellent diagnostic discrimination (AUC 0.985; 95% CI, 0.974–0.996), with sensitivity and specificity of 96.4% and 97.3%, respectively. Diagnostic performance was consistent across disease stages, tumor-size categories, molecular subtypes, mammographic categories, and breast-density groups. Trx1 sensitivity remained high in dense breasts (98.9% in BI-RADS density grades C/D), whereas mammographic sensitivity was substantially lower (67.0%). Integration of Trx1 with mammographic assessment improved diagnostic discrimination (AUC 0.980) and provided greater net benefit in decision curve analysis, particularly among women with low-suspicion or indeterminate imaging findings. Conclusions: Circulating Trx1 demonstrated robust diagnostic performance across disease stages, tumor-size categories, and clinically relevant patient subgroups while providing biologically independent information that complements mammographic assessment. Although this retrospective multicenter study requires prospective validation in independent diagnostic populations, Trx1 may serve as a clinically useful adjunct to imaging-based breast cancer evaluation, particularly in diagnostically uncertain settings.

Backgroundand Objectives: We examined long-term breast reconstruction-related procedure use, composition, and provider–location concentration in Korea. Materials and Methods: Monthly aggregate Health Insurance Review and Assessment Service (HIRA) statistics for N7140–N7153 from April 2015 to December 2024 were analyzed using segmented regression, March 2020 and May 2022 breakpoints, calendar-month indicators, and Newey–West standard errors. Supplementary analyses examined nonlinear trends, working days, temporary interruptions, and mastectomy volume. Results: The series comprised 96,988 procedure uses; the annual volume increased 44.9% during 2016–2024. The modeled March 2020 level change was −82.0 uses (95% confidence interval [CI], −118.9 to −45.0; p < 0.001), or 8.5% below the counterfactual. The quadratic-time estimate was −55.7 (95% CI, −91.4 to −19.9; p = 0.002); category-specific findings were less robust. No clear additional level change occurred in May 2022. In the July 2017–December 2024 analysis, the estimated March 2020 level change in reconstruction-related uses per 100 malignant total-mastectomy uses was −1.51 (95% CI, −7.62 to 4.59; p = 0.627). The corresponding exploratory immediate direct-to-implant (DTI) ratio change was +1.77 per 100 mastectomy uses (95% CI, 0.14 to 3.40; p = 0.033). The DTI share increased from 20.7% to 45.1% of all included uses, while the autologous share decreased from 20.2% to 7.0%. DTI provider activity was less concentrated than the other single-code categories across the tested scenarios; the autologous comparison was sensitive in hypothetical nonzero-assignment stress tests. Conclusions: Recorded use increased and shifted toward DTI. The overall procedure-use ratio showed no statistically clear change; this establishes neither equivalence nor that mastectomy volume explains the decline in reconstruction-related use. These aggregate data describe service use, not individual pathways, patient travel, or causal pandemic effects.