The expression of five antigens, associated with transitional cell carcinoma (TCC) of the urinary bladder on biopsies of tumors or normal urothelium, was studied by immunostaining with the corresponding monoclonal antibodies. Both tissue sections and single cell preparations were investigated with either indirect immunoperoxidase staining or immunofluorescence. All 5 antigens were expressed on the majority (70-90%) of sectioned tumor specimens from 44 TCC patients, and 4 of them were similarly expressed on single cell tumor preparations from 26 additional patients. However, in both types of preparation, the degree of expression of these antigens varied from scattered staining of less than 25% of the tumor cells to homogenous staining of all or almost all cells. This degree of expression varied individually for each of the antigens and was not related to the malignancy grade of the tumors. However, as most of the tumors were of grades II or III, no conclusions regarding the relationship of antigen expression to the aggressiveness of the tumors can be drawn. In any event, all tumors expressed at least one and mostly several of these antigens. Antigen expression on biopsies of normal bladder mucosa from TCC patients or on urothelial biopsies from patients with prostate hyperplasia was also observed on single cell specimens (34 patients) but not on sectioned material (9 patients). However, the frequency of positive specimens was much lower (4-20%). Moreover, the number of cells expressing one or, occasionally, several of the antigens in normal urothelium was small (usually less than 5%). Because of these marked differences in antigen expression between tumors and normal tissue, the results indicate that a combination of 3-5 of the antibodies used in this study may be suitable for diagnostic purposes.
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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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