Limits...
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

Immunohistochemical labelling of uroplakins (brown reaction products) in urothelial tumour (A–C), resection border (D–F) and uninvolved urothelium (G–I) from patients with noninvasive (pTa) or lamina propria invasive (pT1) papillary carcinomas. Urothelial tumour with (A) uroplakin-positive superficial cell layer and individual uroplakin-positive intermediate cells, (B) uroplakin-negative urothelium and (C) urothelium containing rare uroplakin-positive cells. Resection border with (D,F) uroplakin-positive and uroplakin-negative regions of urothelium and (E) completely uroplakin-negative urothelium. Uninvolved urothelium with (G,H) small and (I) large regions of uroplakin-positive superficial cells. In the region with uroplakin-positive superficial cells, some intermediate cells are also uroplakin-positive. Scale bars: 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-rado-47-04-338: Immunohistochemical labelling of uroplakins (brown reaction products) in urothelial tumour (A–C), resection border (D–F) and uninvolved urothelium (G–I) from patients with noninvasive (pTa) or lamina propria invasive (pT1) papillary carcinomas. Urothelial tumour with (A) uroplakin-positive superficial cell layer and individual uroplakin-positive intermediate cells, (B) uroplakin-negative urothelium and (C) urothelium containing rare uroplakin-positive cells. Resection border with (D,F) uroplakin-positive and uroplakin-negative regions of urothelium and (E) completely uroplakin-negative urothelium. Uninvolved urothelium with (G,H) small and (I) large regions of uroplakin-positive superficial cells. In the region with uroplakin-positive superficial cells, some intermediate cells are also uroplakin-positive. Scale bars: 100 μm.

Mentions: Papillary carcinomas showed no direct correlation between uroplakin expression and carcinoma staging and grading, which was consistent with previously published data.12,13 In order to compare uroplakin expression in different urothelial regions, immunohistochemical labelling of uroplakins was performed on the paraffin sections from (i) the urothelial tumour, (ii) resection border and (iii) un-involved urothelium. In general, uroplakin expression was lower in all patients compared to normal urothelium. (i) Urothelium of urothelial tumours showed three distinct types of uroplakin labelling patterns. In the first type, urothelium was covered by continuous layer of uroplakin-positive superficial cell and it also contained individual uroplakin-positive intermediate cells (Figure 2A). In the second type, urothelium was completely uroplakin-negative (Figure 2B). In the third type, urothelium contained individual uroplakin-positive cells, which were scattered throughout all cell layers (Figure 2C). (ii) Urothelium of resection borders also revealed heterogeneous labelling patterns, which could be placed into three categories. One type of resection border contained urothelium with normal histology, but discontinuous uroplakin expression in the superficial cell layer (Figure 2D). Another type of resection border was composed of urothelium, which had the same histopathologic characteristics as tumours. Here, urothelium was also completely uroplakin-negative as was the case in the neighbouring tumour (Figure 2E). Yet another type of resection border contained hyperplastic urothelium, which was covered with large stretches of uroplakin-positive superficial cells, alternating with large stretches of uroplakin-negative superficial cells. Urothelial regions covered with uroplakin-positive superficial cells contained uroplakin-positive intermediate cells. These uroplakin-positive cells were always found just beneath the superficial cell layer (Figure 2F). (iii) Uninvolved urothelia exhibited normal histology; however their superficial cells were either uroplakin-positive or uroplakin-negative (Figure 2G–I). The extent of uroplakin-positive versus uroplakin-negative regions varied to a great degree. As described for tumours and resection borders, uninvolved urothelium also contained individual uroplakin-positive intermediate cells, usually underlying uroplakin-positive superficial cells (Figure 2I).


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

Zupancic D, Romih R - Radiol Oncol (2013)

Immunohistochemical labelling of uroplakins (brown reaction products) in urothelial tumour (A–C), resection border (D–F) and uninvolved urothelium (G–I) from patients with noninvasive (pTa) or lamina propria invasive (pT1) papillary carcinomas. Urothelial tumour with (A) uroplakin-positive superficial cell layer and individual uroplakin-positive intermediate cells, (B) uroplakin-negative urothelium and (C) urothelium containing rare uroplakin-positive cells. Resection border with (D,F) uroplakin-positive and uroplakin-negative regions of urothelium and (E) completely uroplakin-negative urothelium. Uninvolved urothelium with (G,H) small and (I) large regions of uroplakin-positive superficial cells. In the region with uroplakin-positive superficial cells, some intermediate cells are also uroplakin-positive. Scale bars: 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-rado-47-04-338: Immunohistochemical labelling of uroplakins (brown reaction products) in urothelial tumour (A–C), resection border (D–F) and uninvolved urothelium (G–I) from patients with noninvasive (pTa) or lamina propria invasive (pT1) papillary carcinomas. Urothelial tumour with (A) uroplakin-positive superficial cell layer and individual uroplakin-positive intermediate cells, (B) uroplakin-negative urothelium and (C) urothelium containing rare uroplakin-positive cells. Resection border with (D,F) uroplakin-positive and uroplakin-negative regions of urothelium and (E) completely uroplakin-negative urothelium. Uninvolved urothelium with (G,H) small and (I) large regions of uroplakin-positive superficial cells. In the region with uroplakin-positive superficial cells, some intermediate cells are also uroplakin-positive. Scale bars: 100 μm.
Mentions: Papillary carcinomas showed no direct correlation between uroplakin expression and carcinoma staging and grading, which was consistent with previously published data.12,13 In order to compare uroplakin expression in different urothelial regions, immunohistochemical labelling of uroplakins was performed on the paraffin sections from (i) the urothelial tumour, (ii) resection border and (iii) un-involved urothelium. In general, uroplakin expression was lower in all patients compared to normal urothelium. (i) Urothelium of urothelial tumours showed three distinct types of uroplakin labelling patterns. In the first type, urothelium was covered by continuous layer of uroplakin-positive superficial cell and it also contained individual uroplakin-positive intermediate cells (Figure 2A). In the second type, urothelium was completely uroplakin-negative (Figure 2B). In the third type, urothelium contained individual uroplakin-positive cells, which were scattered throughout all cell layers (Figure 2C). (ii) Urothelium of resection borders also revealed heterogeneous labelling patterns, which could be placed into three categories. One type of resection border contained urothelium with normal histology, but discontinuous uroplakin expression in the superficial cell layer (Figure 2D). Another type of resection border was composed of urothelium, which had the same histopathologic characteristics as tumours. Here, urothelium was also completely uroplakin-negative as was the case in the neighbouring tumour (Figure 2E). Yet another type of resection border contained hyperplastic urothelium, which was covered with large stretches of uroplakin-positive superficial cells, alternating with large stretches of uroplakin-negative superficial cells. Urothelial regions covered with uroplakin-positive superficial cells contained uroplakin-positive intermediate cells. These uroplakin-positive cells were always found just beneath the superficial cell layer (Figure 2F). (iii) Uninvolved urothelia exhibited normal histology; however their superficial cells were either uroplakin-positive or uroplakin-negative (Figure 2G–I). The extent of uroplakin-positive versus uroplakin-negative regions varied to a great degree. As described for tumours and resection borders, uninvolved urothelium also contained individual uroplakin-positive intermediate cells, usually underlying uroplakin-positive superficial cells (Figure 2I).

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