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Heterogeneity of uroplakin localization in human normal urothelium, papilloma and papillary carcinoma.

Zupancic D, Romih R - Radiol Oncol (2013)

Bottom Line: We compared uroplakin expression and ultrastructural localization in human normal urothelium, papilloma and papillary carcinoma.Diverse uroplakin expression was found in papilloma and papillary carcinoma.In patients with papilloma and papillary carcinoma immunolabelling of uroplakins at ultrastructural level shows aberrant urothelial differentiation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cell Biology, Faculty of Medicine, Ljubljana, Slovenia.

ABSTRACT

Background: Uroplakins are differentiation-related membrane proteins of urothelium. We compared uroplakin expression and ultrastructural localization in human normal urothelium, papilloma and papillary carcinoma. Because of high recurrence rate of these tumours, treated by transurethral resection, we investigated urothelial tumour, resection border and uninvolved urothelium.

Patients and methods: Urinary bladder samples were obtained from tumour free control subjects and patients with papilloma and papillary carcinoma. Immunohistochemical and immunoelectron labelling of uroplakins were performed.

Results: In normal human urothelium with continuous uroplakin-positive superficial cell layer uroplakins were localized to flattened mature fusiform vesicles and apical plasma membrane of umbrella cells. Diverse uroplakin expression was found in papilloma and papillary carcinoma. Three aberrant differentiation stages of urothelial cells, not found in normal urothelium, were recognized in tumours. Diverse uroplakin expression and aberrant differentiation were occasionally found in resection border and in uninvolved urothelium.

Conclusions: We demonstrated here that uroplakin expression and localization in urothelial tumours is altered when compared to normal urothelium. In patients with papilloma and papillary carcinoma immunolabelling of uroplakins at ultrastructural level shows aberrant urothelial differentiation. It is possible that aberrant differentiation stages of urothelial cells in resection border and in uninvolved urothelium contribute to high recurrence rate.

No MeSH data available.


Related in: MedlinePlus

Immunoelectron microscopy of uroplakins in urothelial tumours. (A,B) papilloma, (C) tumour region of pTa G1, (D) tumour region of pT1 G1–2, (E) uninvolved urothelium of pTa G1–2. (A) Uroplakin-positive superficial (SC) and uroplakin-positive intermediate cells (IC) are shown. Note dilatations of intercellular spaces (asterisks) and prominent cytoplasmic processes that interconnect neighbouring cells. (B) Superficial cell with uroplakin-positive apical plasma membrane (arrowheads) and weakly positive immature fusiform vesicles (arrows). (C) Uroplakin-negative superficial cell with microvilli (arrows) on the apical surface. (D) Intermediate cell with uroplakin-positive transporting vesicles (arrows) and uroplakin-negative plasma membrane (arrowheads). (E) Intermediate cell with numerous mitochondria, uroplakin-positive transporting vesicles and uroplakin-positive plasma membrane (arrowheads). N – nucleus, L – lumen. Scale bars: 1 μm.
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f4-rado-47-04-338: Immunoelectron microscopy of uroplakins in urothelial tumours. (A,B) papilloma, (C) tumour region of pTa G1, (D) tumour region of pT1 G1–2, (E) uninvolved urothelium of pTa G1–2. (A) Uroplakin-positive superficial (SC) and uroplakin-positive intermediate cells (IC) are shown. Note dilatations of intercellular spaces (asterisks) and prominent cytoplasmic processes that interconnect neighbouring cells. (B) Superficial cell with uroplakin-positive apical plasma membrane (arrowheads) and weakly positive immature fusiform vesicles (arrows). (C) Uroplakin-negative superficial cell with microvilli (arrows) on the apical surface. (D) Intermediate cell with uroplakin-positive transporting vesicles (arrows) and uroplakin-negative plasma membrane (arrowheads). (E) Intermediate cell with numerous mitochondria, uroplakin-positive transporting vesicles and uroplakin-positive plasma membrane (arrowheads). N – nucleus, L – lumen. Scale bars: 1 μm.

Mentions: Immunoelectron microscopy of uroplakins confirmed the results of imunohistochemical labelling of urothelial tumours. We observed uroplakin-positive (Figure 4A, B) and uroplakin-negative (Figure 4C) superficial cells in papilloma and in all regions (tumour, resection border, uninvolved urothelium) of pTa and pT1 papillary carcinoma. Uroplakin-positive superficial cells had uroplakins in their apical plasma membranes and cytoplasmic vesicles. These uroplakin-positive vesicles were smaller and weakly labelled (Figure 4B) when compared to mature fusiform vesicles of normal urothelium (Figure 3B), and therefore represented immature fusiform vesicles. Importantly, mature fusiform vesicles were not detected in any of the samples taken from patients with urothelial tumours, not even in uninvolved urothelium. Uroplakin-negative superficial cells had microvilli on their apical surface and small, rounded vesicles in their cytoplasm (Figure 4C).


Heterogeneity of uroplakin localization in human normal urothelium, papilloma and papillary carcinoma.

Zupancic D, Romih R - Radiol Oncol (2013)

Immunoelectron microscopy of uroplakins in urothelial tumours. (A,B) papilloma, (C) tumour region of pTa G1, (D) tumour region of pT1 G1–2, (E) uninvolved urothelium of pTa G1–2. (A) Uroplakin-positive superficial (SC) and uroplakin-positive intermediate cells (IC) are shown. Note dilatations of intercellular spaces (asterisks) and prominent cytoplasmic processes that interconnect neighbouring cells. (B) Superficial cell with uroplakin-positive apical plasma membrane (arrowheads) and weakly positive immature fusiform vesicles (arrows). (C) Uroplakin-negative superficial cell with microvilli (arrows) on the apical surface. (D) Intermediate cell with uroplakin-positive transporting vesicles (arrows) and uroplakin-negative plasma membrane (arrowheads). (E) Intermediate cell with numerous mitochondria, uroplakin-positive transporting vesicles and uroplakin-positive plasma membrane (arrowheads). N – nucleus, L – lumen. Scale bars: 1 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3814278&req=5

f4-rado-47-04-338: Immunoelectron microscopy of uroplakins in urothelial tumours. (A,B) papilloma, (C) tumour region of pTa G1, (D) tumour region of pT1 G1–2, (E) uninvolved urothelium of pTa G1–2. (A) Uroplakin-positive superficial (SC) and uroplakin-positive intermediate cells (IC) are shown. Note dilatations of intercellular spaces (asterisks) and prominent cytoplasmic processes that interconnect neighbouring cells. (B) Superficial cell with uroplakin-positive apical plasma membrane (arrowheads) and weakly positive immature fusiform vesicles (arrows). (C) Uroplakin-negative superficial cell with microvilli (arrows) on the apical surface. (D) Intermediate cell with uroplakin-positive transporting vesicles (arrows) and uroplakin-negative plasma membrane (arrowheads). (E) Intermediate cell with numerous mitochondria, uroplakin-positive transporting vesicles and uroplakin-positive plasma membrane (arrowheads). N – nucleus, L – lumen. Scale bars: 1 μm.
Mentions: Immunoelectron microscopy of uroplakins confirmed the results of imunohistochemical labelling of urothelial tumours. We observed uroplakin-positive (Figure 4A, B) and uroplakin-negative (Figure 4C) superficial cells in papilloma and in all regions (tumour, resection border, uninvolved urothelium) of pTa and pT1 papillary carcinoma. Uroplakin-positive superficial cells had uroplakins in their apical plasma membranes and cytoplasmic vesicles. These uroplakin-positive vesicles were smaller and weakly labelled (Figure 4B) when compared to mature fusiform vesicles of normal urothelium (Figure 3B), and therefore represented immature fusiform vesicles. Importantly, mature fusiform vesicles were not detected in any of the samples taken from patients with urothelial tumours, not even in uninvolved urothelium. Uroplakin-negative superficial cells had microvilli on their apical surface and small, rounded vesicles in their cytoplasm (Figure 4C).

Bottom Line: We compared uroplakin expression and ultrastructural localization in human normal urothelium, papilloma and papillary carcinoma.Diverse uroplakin expression was found in papilloma and papillary carcinoma.In patients with papilloma and papillary carcinoma immunolabelling of uroplakins at ultrastructural level shows aberrant urothelial differentiation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cell Biology, Faculty of Medicine, Ljubljana, Slovenia.

ABSTRACT

Background: Uroplakins are differentiation-related membrane proteins of urothelium. We compared uroplakin expression and ultrastructural localization in human normal urothelium, papilloma and papillary carcinoma. Because of high recurrence rate of these tumours, treated by transurethral resection, we investigated urothelial tumour, resection border and uninvolved urothelium.

Patients and methods: Urinary bladder samples were obtained from tumour free control subjects and patients with papilloma and papillary carcinoma. Immunohistochemical and immunoelectron labelling of uroplakins were performed.

Results: In normal human urothelium with continuous uroplakin-positive superficial cell layer uroplakins were localized to flattened mature fusiform vesicles and apical plasma membrane of umbrella cells. Diverse uroplakin expression was found in papilloma and papillary carcinoma. Three aberrant differentiation stages of urothelial cells, not found in normal urothelium, were recognized in tumours. Diverse uroplakin expression and aberrant differentiation were occasionally found in resection border and in uninvolved urothelium.

Conclusions: We demonstrated here that uroplakin expression and localization in urothelial tumours is altered when compared to normal urothelium. In patients with papilloma and papillary carcinoma immunolabelling of uroplakins at ultrastructural level shows aberrant urothelial differentiation. It is possible that aberrant differentiation stages of urothelial cells in resection border and in uninvolved urothelium contribute to high recurrence rate.

No MeSH data available.


Related in: MedlinePlus