Objective: To investigate galectin-8 expression patterns in normal urothelium and bladder cancer specimens and to elucidate its prognostic value.
Materials And Methods: 162 samples of non-muscle-invasive transitional cell carcinoma, 25 samples of muscle-invasive transitional cell carcinoma and 10 samples of normal urothelium were investigated by immunohistochemistry using tissue microarrays. Complete patient and tumor characteristics were compared with galectin-8 staining patterns. The likelihood of tumor recurrence and progression was analyzed based on a 3-year follow-up.
Results: Loss of galectin-8 was associated with the likelihood of tumor recurrence in univariate (p < 0.05) and multivariate analyses (p < 0.01). No significance was observed for tumor progression. Patients whose specimens showed weak galectin-8 expression had a shorter recurrence-free interval (42 vs. 12 months; p < 0.01, log-rank test). All of the 10 normal urothelium samples showed high galectin-8 expression. Decreased staining was found to be associated with higher tumor stages and grades (p < 0.0001, one-way ANOVA). A significant difference was found comparing normal urothelium with any tumor stage (p < 0.01), pTa vs. pT1 tumors (p < 0.05) and non-muscle-invasive vs. muscle-invasive tumors (p < 0.0001).
Conclusions: Loss of galectin-8 might be an early step in the development of malignant lesions of the bladder and is a significant independent predictor of recurrence.
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http://dx.doi.org/10.1159/000328439 | DOI Listing |
Nat Genet
January 2025
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
December 2024
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Background: Urothelial carcinoma (UC) is a common type of malignant disease; however, the diagnostic and prognostic markers of upper urinary tract urothelial cancer (UTUC) remain poorly understood because of its rarity.
Methods: To clarify the clinicopathological significance of granulocyte-colony stimulating factor (G-CSF) in UTUC, we analyzed the expression and distribution of G-CSF in 112 upper tract urothelial carcinoma (UTUC) samples with immunohistochemistry.
Results: In normal urothelium, G-CSF expression was weak or absent, whereas high expression of G-CSF was observed in UTUC tissues, both in tumor cells (TCs) and stromal cells (SCs).
Int J Gynecol Pathol
December 2024
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine.
Transitional cell metaplasia (TCM) resembling benign urothelium is commonly seen around the distal fallopian tube and/or neighboring mesothelial surface; however, its histogenesis remains largely unknown. We observed the emergence of a cytokeratin (CK) 17-positive reserve cell layer in early TCM foci beneath the tubal epithelium, leading us to hypothesize that TCM could be derived from reserve cells. To elucidate the histogenetic process of TCM, we analyzed the histomorphologic features and immunoprofiles for CK17, CK5/6, p63, GATA-3, estrogen receptor (ER), and androgen receptor (AR) in TCM foci arising in the tubal epithelium (31 foci) and pelvic mesothelium (35 foci).
View Article and Find Full Text PDFJ Biomed Opt
December 2024
Osaka University, Graduate School of Engineering, Osaka, Japan.
Significance: For therapeutic approaches for upper tract urothelial carcinomas, the absorption and reduced scattering coefficients of these tissues are essential parameters to quantitatively evaluate the distribution of light treatment effects.
Aim: The and spectra of the human ureter, fatty tissue, ureteral and renal pelvic carcinomas, and porcine ureter and fatty tissue are measured over 400 to 700 nm to evaluate projected light penetration depths .
Approach: The optical properties were determined with a double integrating sphere optical system and inverse Monte Carlo methods.
Diagnostics (Basel)
November 2024
Department of Human Physiology, Human Histology, Pathology, and Sports Physical Education, University of Malaga (UMA), 29071 Málaga, Spain.
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