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Incident urothelial cancer in the Malmö Diet and Cancer Study: cohort characteristics and further validation of ezrin as a prognostic biomarker.

Wennersten C, Andersson G, Boman K, Nodin B, Gaber A, Jirström K - Diagn Pathol (2014)

Bottom Line: Membranous but not cytoplasmic ezrin was significantly reduced in recurrent compared to primary tumours (p < 0.001).Low cytoplasmic and membranous ezrin expression were associated with more advanced T-stage (p = 0.004, p < 0.001) and high-grade tumours (p = 0.025, p < 0.001), but not with age, sex, tumour location or smoking status.Both low cytoplasmic and membranous ezrin staining were associated with a significantly reduced 5-year OS (HR = 1.65; 95% CI 1.06-2.57 and HR = 2.51, 95% CI 1.52-4.17), but only low membranous ezrin remained prognostic after adjustment for age, sex, stage, grade and smoking status (HR = 1.69, 95% CI 1.00-2.85).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, 221 85, Sweden. karin.jirstrom@med.lu.se.

ABSTRACT

Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with poor prognosis in urothelial bladder cancer in several independent studies. The present study provides a first description of clinicopathological characteristics of incident urothelial cancers, not only located to the bladder, in the prospective, population-based cohort study Malmö Diet and Cancer. In addition, the prognostic value of ezrin expression is validated in primary tumours, and the longitudinal expression of ezrin examined in a subset of primary and recurrent tumours (n=28).

Methods: Among a total number of 355 incident tumours registered up until Dec 31 2010, 335 were located to the bladder. Immunohistochemical expression of cytoplasmic and membranous ezrin was evaluated in tissue microarrays with primary tumours from 272 cases and recurrent tumours from 28 cases. A combined score of the minimum, mean and maximum fraction and percentage of staining was calculated. Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test, univariable and multivariable Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin expression on 5-year overall survival (OS).

Results: Ezrin expression could be evaluated in 263/272 primary and all 28 recurrent tumours. Membranous but not cytoplasmic ezrin was significantly reduced in recurrent compared to primary tumours (p < 0.001). Low cytoplasmic and membranous ezrin expression were associated with more advanced T-stage (p = 0.004, p < 0.001) and high-grade tumours (p = 0.025, p < 0.001), but not with age, sex, tumour location or smoking status. Both low cytoplasmic and membranous ezrin staining were associated with a significantly reduced 5-year OS (HR = 1.65; 95% CI 1.06-2.57 and HR = 2.51, 95% CI 1.52-4.17), but only low membranous ezrin remained prognostic after adjustment for age, sex, stage, grade and smoking status (HR = 1.69, 95% CI 1.00-2.85).

Conclusions: This study provides a first description of the clinicopathological characteristics of 355 incident urothelial cancers in the Malmö Diet and Cancer Study up until 2010. In addition, the value of ezrin expression as a prognostic biomarker is further consolidated in this type of cancer.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_189.

No MeSH data available.


Related in: MedlinePlus

Sample immunohistochemical images. Images representing A) a primary tumour with strong membranous and moderate cytoplasmic ezrin expression in nearly 100% of cells, B) a primary tumour with negative membranous and weak, focally moderate cytoplasmic staining (note strongly staining stromal lymphocytes). C) A primary tumour with negative membranous and focally weak cytoplasmic ezrin expression and D) subsequent metastasis to the small intestine with negative membranous and moderate to strong cytoplasmic staining. E) A primary tumour with moderate to strong membranous ezrin expression in approximately 25% and weak cytoplasmic staining in the majority of cells and F) local recurrence with membranous ezrin expression in <5% and moderate to strong cytoplasmic ezrin expression in > 50% of cells.
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Fig2: Sample immunohistochemical images. Images representing A) a primary tumour with strong membranous and moderate cytoplasmic ezrin expression in nearly 100% of cells, B) a primary tumour with negative membranous and weak, focally moderate cytoplasmic staining (note strongly staining stromal lymphocytes). C) A primary tumour with negative membranous and focally weak cytoplasmic ezrin expression and D) subsequent metastasis to the small intestine with negative membranous and moderate to strong cytoplasmic staining. E) A primary tumour with moderate to strong membranous ezrin expression in approximately 25% and weak cytoplasmic staining in the majority of cells and F) local recurrence with membranous ezrin expression in <5% and moderate to strong cytoplasmic ezrin expression in > 50% of cells.

Mentions: Following antibody optimisation and staining, ezrin expression could be evaluated in 263/272 (96.7%) primary tumours and all 28 metastases. Lost cases were either a result of complete tissue loss during IHC preparation or an insufficient quantity of tumour tissue. Sample IHC images are shown in Figure 2.Figure 2


Incident urothelial cancer in the Malmö Diet and Cancer Study: cohort characteristics and further validation of ezrin as a prognostic biomarker.

Wennersten C, Andersson G, Boman K, Nodin B, Gaber A, Jirström K - Diagn Pathol (2014)

Sample immunohistochemical images. Images representing A) a primary tumour with strong membranous and moderate cytoplasmic ezrin expression in nearly 100% of cells, B) a primary tumour with negative membranous and weak, focally moderate cytoplasmic staining (note strongly staining stromal lymphocytes). C) A primary tumour with negative membranous and focally weak cytoplasmic ezrin expression and D) subsequent metastasis to the small intestine with negative membranous and moderate to strong cytoplasmic staining. E) A primary tumour with moderate to strong membranous ezrin expression in approximately 25% and weak cytoplasmic staining in the majority of cells and F) local recurrence with membranous ezrin expression in <5% and moderate to strong cytoplasmic ezrin expression in > 50% of cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4195979&req=5

Fig2: Sample immunohistochemical images. Images representing A) a primary tumour with strong membranous and moderate cytoplasmic ezrin expression in nearly 100% of cells, B) a primary tumour with negative membranous and weak, focally moderate cytoplasmic staining (note strongly staining stromal lymphocytes). C) A primary tumour with negative membranous and focally weak cytoplasmic ezrin expression and D) subsequent metastasis to the small intestine with negative membranous and moderate to strong cytoplasmic staining. E) A primary tumour with moderate to strong membranous ezrin expression in approximately 25% and weak cytoplasmic staining in the majority of cells and F) local recurrence with membranous ezrin expression in <5% and moderate to strong cytoplasmic ezrin expression in > 50% of cells.
Mentions: Following antibody optimisation and staining, ezrin expression could be evaluated in 263/272 (96.7%) primary tumours and all 28 metastases. Lost cases were either a result of complete tissue loss during IHC preparation or an insufficient quantity of tumour tissue. Sample IHC images are shown in Figure 2.Figure 2

Bottom Line: Membranous but not cytoplasmic ezrin was significantly reduced in recurrent compared to primary tumours (p < 0.001).Low cytoplasmic and membranous ezrin expression were associated with more advanced T-stage (p = 0.004, p < 0.001) and high-grade tumours (p = 0.025, p < 0.001), but not with age, sex, tumour location or smoking status.Both low cytoplasmic and membranous ezrin staining were associated with a significantly reduced 5-year OS (HR = 1.65; 95% CI 1.06-2.57 and HR = 2.51, 95% CI 1.52-4.17), but only low membranous ezrin remained prognostic after adjustment for age, sex, stage, grade and smoking status (HR = 1.69, 95% CI 1.00-2.85).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, 221 85, Sweden. karin.jirstrom@med.lu.se.

ABSTRACT

Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with poor prognosis in urothelial bladder cancer in several independent studies. The present study provides a first description of clinicopathological characteristics of incident urothelial cancers, not only located to the bladder, in the prospective, population-based cohort study Malmö Diet and Cancer. In addition, the prognostic value of ezrin expression is validated in primary tumours, and the longitudinal expression of ezrin examined in a subset of primary and recurrent tumours (n=28).

Methods: Among a total number of 355 incident tumours registered up until Dec 31 2010, 335 were located to the bladder. Immunohistochemical expression of cytoplasmic and membranous ezrin was evaluated in tissue microarrays with primary tumours from 272 cases and recurrent tumours from 28 cases. A combined score of the minimum, mean and maximum fraction and percentage of staining was calculated. Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test, univariable and multivariable Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin expression on 5-year overall survival (OS).

Results: Ezrin expression could be evaluated in 263/272 primary and all 28 recurrent tumours. Membranous but not cytoplasmic ezrin was significantly reduced in recurrent compared to primary tumours (p < 0.001). Low cytoplasmic and membranous ezrin expression were associated with more advanced T-stage (p = 0.004, p < 0.001) and high-grade tumours (p = 0.025, p < 0.001), but not with age, sex, tumour location or smoking status. Both low cytoplasmic and membranous ezrin staining were associated with a significantly reduced 5-year OS (HR = 1.65; 95% CI 1.06-2.57 and HR = 2.51, 95% CI 1.52-4.17), but only low membranous ezrin remained prognostic after adjustment for age, sex, stage, grade and smoking status (HR = 1.69, 95% CI 1.00-2.85).

Conclusions: This study provides a first description of the clinicopathological characteristics of 355 incident urothelial cancers in the Malmö Diet and Cancer Study up until 2010. In addition, the value of ezrin expression as a prognostic biomarker is further consolidated in this type of cancer.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_189.

No MeSH data available.


Related in: MedlinePlus