Can tissue microarray-based analysis of protein expression predict recurrence of stage Ta bladder cancer?

Guðjónsson, Sigurður; Bendahl, Pär‐Ola; Chebil, Gunilla; Höglund, Mattias; Lindgren, David; Lundberg, Lena-Maria; Lövgren, Kristina; Fernö, Mårten; Månsson, Wiking

doi:10.3109/00365599.2011.568956

Cited by 12 publications

(10 citation statements)

References 31 publications

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“…Some authors have discussed the accuracy of TMA immunohistochemistry in measuring protein expression (26), but the advantages of the method outperform the disadvantages in terms of standardization of reaction and analysis and have been applied in the evaluation of many prognostic markers in different tumors including urothelial carcinoma for more than 20 years (27).…”

Section: Discussionmentioning

confidence: 99%

Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

et al. 2012

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ARTIcLE INFO _________________________________________________________ ___________________Introduction: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and α-, β-and γ-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. Materials and Methods: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. Results: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of α-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). Conclusions: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of α-catenin expression is related to tumor size in upper tract urothelial carcinomas.

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Section: Discussionmentioning

confidence: 99%

Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

et al. 2012

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“…Recently, Gudjonsson et al [16] described using IHC to evaluate the protein epidermal growth factor receptor (EGFR) in both TMAs and whole sections, and the results differed between the two approaches. Accordingly, these investigators questioned whether the assessments of protein expression in TMAs can be generalized.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports from our group indicate that LVI was associated with progression while this was not the case for clinical and other histopathological variables or HER2 immunohistochemical staining [14, 15]. We have now investigated a panel of biomarkers, visualization was achieved by IHC on whole sections of tumour material opposed to tissue microarrays (TMAs), the latter having been shown to provide inferior concordance [16]. We paid special attention to well-known cell cycle regulators, such as cyclin D1, p53, pRb, p21, and p16.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Evaluation of Cell Cycle Regulators: Impact on Predicting Prognosis in Stage T1 Urinary Bladder Cancer

et al. 2012

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Background and Objective. The cell cycle is regulated by proteins at different checkpoints, and dysregulation of this cycle plays a role in carcinogenesis. Matrix metalloproteinases (MMPs) are enzymes that degrade collagen and promote tumour infiltration. The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder (UCB). Patients and Methods. This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder. Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs. Results. Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence. Also, normal p16 expression was related to a lower risk of tumour progression. MMP2, p21, cyclin D1, and pRb showed no significant results that could estimate progression or recurrence. Conclusions. Normal p16 expression is associated with a lower risk of tumour progression, but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB.

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“…The combination of WHO 2004 grading with FGFR3 mutation status facilitated improved risk stratification for patients exhibiting high-grade, non-muscle-invasive urothelial BC ( 5 ). However, studies of FGFR3 immunoreactivity and its clinical significance are uncommon ( 20 , 21 ). Immunohistochemical detection of the FGFR3 receptor may provide a simpler, cheaper and faster approach for histopathological practice, compared with the current method of determination of FGFR3 mutation status.…”

Section: Introductionmentioning

confidence: 99%

Positive fibroblast growth factor receptor 3 immunoreactivity is associated with low-grade non-invasive urothelial bladder cancer

et al. 2015

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In addition to conventional clinicopathological parameters, molecular markers are also required in order to predict the course of disease in patients with urothelial bladder cancer (BC). Little is known about fibroblast growth factor receptor 3 (FGFR3) immunoreactivity and the clinical significance it may possess with regard to BC. The present study aimed to investigate the immunoreactivity of FGFR3 in primary urothelial bladder tumours, with regard to clinicopathological features and FGFR3 mutation status. Tissue microarrays were used to immunohistochemically analyse FGFR3 expression in 255 primary, unselected patients with BC. FGFR3 mutations were detected using SNaPshot analysis. Positive FGFR3 immunoreactivity was identified in 113/207 analysable cases (54.6%), and was significantly associated with FGFR3 mutation (P<0.001), low tumour stage (P<0.001), low histological grade (P<0.001) and a papillary growth pattern (P<0.001). Positive FGFR3 immunostaining (P=0.002) and FGFR3 mutation (P=0.002) were found to be significantly associated with increased disease-specific survival following univariate analysis, demonstrating a median follow-up period of 75 months. Using multivariate analyses, FGFR3 immunoreactivity was found not to be independent of classical pathological parameters. Immunohistochemical expression of FGFR3 is an early occurrence during the carcinogenesis of papillary non-invasive BC. The presence of FGFR3 immunoreactivity in non-invasive papillary urothelial carcinomas may be utilised as an indicator of tumours possessing low-grade features and good prognosis.

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Can tissue microarray-based analysis of protein expression predict recurrence of stage Ta bladder cancer?

Cited by 12 publications

References 31 publications

Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

Immunohistochemical Evaluation of Cell Cycle Regulators: Impact on Predicting Prognosis in Stage T1 Urinary Bladder Cancer

Positive fibroblast growth factor receptor 3 immunoreactivity is associated with low-grade non-invasive urothelial bladder cancer

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