Succinate dehydrogenase (SDH)–deficient renal cell carcinoma is a recently recognized distinct subtype of renal cell carcinoma in the 2016 World Health Organization classification. It is associated with SDH gene germline mutations, which also cause paraganglioma/pheochromocytoma, gastrointestinal stromal tumor, and pituitary adenoma. The tumor most commonly presents in young adulthood. The tumors are arranged in solid nests or in tubules and frequently show cystic change. The tumors are composed of cuboidal to oval cells with round nuclei, dispersed chromatin, and inconspicuous nucleoli. The cytoplasm is eosinophilic or flocculent but not truly oncocytic. The most distinctive histologic feature is the presence of cytoplasmic vacuoles or inclusions. Loss of SDH subunit B immunostaining is needed for a definite diagnosis. The prognosis is good for low-grade tumors but worse for tumors with high-grade nuclei, sarcomatoid change, or coagulative necrosis. Long-term follow-up is indicated.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer as it shows a high capacity for metastasis and poor prognoses. Metabolic reprogramming is one of the hallmarks of cancer, and aberrant glycolysis was reported to be upregulated in TNBC. Thus, identifying metabolic biomarkers for diagnoses and investigating cross-talk between glycolysis and invasiveness could potentially enable the development of therapeutics for patients with TNBC. In order to determine novel and reliable metabolic biomarkers for predicting clinical outcomes of TNBC, we analyzed transcriptome levels of glycolysis-related genes in various subtypes of breast cancer from public databases and identified a distinct glycolysis gene signature, which included ENO1, SLC2A6, LDHA, PFKP, PGAM1, and GPI, that was elevated and associated with poorer prognoses of TNBC patients. Notably, we found a transcription factor named Y-box-binding protein 1 (YBX1) to be strongly associated with this glycolysis gene signature, and it was overexpressed in TNBC. A mechanistic study further validated that YBX1 was upregulated in TNBC cell lines, and knockdown of YBX1 suppressed expression of those glycolytic genes. Moreover, YBX1 expression was positively associated with epithelial-to-mesenchymal transition (EMT) genes in breast cancer patients, and suppression of YBX1 downregulated expressions of EMT-related genes and tumor migration and invasion in MDA-MB-231 and BT549 TNBC cells. Our data revealed an YBX1-glycolysis-EMT network as an attractive diagnostic marker and metabolic target in TNBC patients.

Colon cancer is the third most common cancer in the world and the second most common cause of cancer-related mortality. Molecular biomarkers for colon cancer have undergone vigorous discovery and validation. Recent studies reported that overexpression of podocalyxin-like protein 1 (PODXL) is associated with distant metastasis and poor prognosis across several types of malignancies. Its role and underlying molecular mechanism, however, are not yet fully understood. In the present study, we revealed that the Hippo transducer, the transcriptional coactivator with PDZ-binding motif (TAZ), acts as a downstream mediator of PODXL in colon cancer. Inhibition of PODXL resulted in the suppression of TAZ signaling and the downregulation of Hippo downstream genes. Moreover, PODXL plays a critical role in cancer stemness, invasiveness, and sensitivity to chemotherapies in colon cancer HCT15 cells. Notably, expression of PODXL showed a positive correlation with stem-like and epithelial-mesenchymal transition (EMT) core signatures, and was associated with poor survival outcomes in patients with colon cancer. These findings provide novel insights into the molecular mechanism of PODXL-mediated tumorigenesis in colon cancer.

In the Paris System (TPS), standardized cytomorphological criteria and diagnostic categories were proposed for reporting urine cytology. To evaluate the diagnostic agreement and interobserver concordance for assessing TPS criteria, the Taiwan Society of Clinical Cytology organized an online survey with 10 atypical urine cytology cases. A total of 137 participants completed the survey. The mean agreement of diagnosis was 51.2%, ranging from 34.3% to 83.2% for each case. For 60% (6/10) of cases, the agreement was <50%. The interobserver concordance of diagnosis and cytological criteria assessment showed poor agreement. The nuclear-to-cytoplasmic (N/C) ratio had the highest kappa value of 0.386, indicating a significantly higher interobserver concordance and reproducibility than the other three TPS criteria. The correct rate of assessing the N/C ratio increased as the N/C ratio increased (correlation coefficient: 0.891, p < 0.01). Three cases with an N/C ratio near 0.5 were overestimated. Poor interobserver concordance of diagnosis and TPS criteria was revealed. Compared with other cytological features, the N/C ratio assessment was quantitative and more reproducible, but a tendency to overestimate cells was noted when the N/C ratio was approximately 0.5. Continuing education programs should emphasize the accurate assessment of N/C ratio to improve the application of TPS.