Expression of Fibroblast Growth Factor Receptor 3 in the Recurrence of Non-Muscle-Invasive Urothelial Carcinoma of the Bladder

Maeng, Young-Hee; Eun, Su-Yong; Huh, Jung–Sik

doi:10.4111/kju.2010.51.2.94

Cited by 21 publications

(17 citation statements)

References 26 publications

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“…Clinical studies are currently focusing on this HPV-positive subpopulation [37]. The FGFR3 amplification observed by the previous study in a mixed HPV-negative HNSCC cohort was not observed in the OSCC and OPSCC cohorts in this study [30]. An explanation could be that the FGFR3 gene is amplified in HNSCC tumors other than OSCC and OPSCC or gene amplification is not detected by our FISH analysis due to the arbitrarily selected ratio and cut-off values.…”

Section: Quantitative Reverse Transcription Polymerase Chainmentioning

confidence: 54%

“…This is in contrast to multiple myeloma and breast cancer, in which FGFR3 protein expression has been related to poor progression-free survival and overall survival [23,24]. For transitional cell carcinoma, the prognostic value for FGFR3 expression is still a subject of debate [18,19,[29][30][31][32][33][34].…”

Section: Quantitative Reverse Transcription Polymerase Chainmentioning

confidence: 99%

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Fibroblast growth factor receptor 3 protein is overexpressed in oral and oropharyngeal squamous cell carcinoma

et al. 2015

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Fibroblast growth factor receptor 3 (FGFR3) is a member of the fibroblast growth factor receptor tyrosine kinase family. It has been identified as a promising therapeutic target in multiple types of cancer. We have investigated FGFR3 protein expression and FGFR3 gene copy‐numbers in a single well‐documented cohort of oral and oropharyngeal squamous cell carcinoma. Tissue microarray sets containing 452 formalin‐fixed paraffin‐embedded tissues were immunohistochemically stained with an anti‐FGFR3 antibody and hybridized with a FGFR3 fluorescence in situ hybridization probe. FGFR3 protein expression was correlated with clinicopathological and survival data, which were retrieved from electronic medical records. FGFR3 mRNA data of 522 head and neck squamous cell carcinoma (HNSCC) were retrieved from The Cancer Genome Atlas (TCGA). Fibroblast growth factor receptor 3 (FGFR3) protein was overexpressed in 48% (89/185) of oral and 59% (124/211) of oropharyngeal squamous cell carcinoma. Overexpression of FGFR3 protein was not related to overall survival or disease‐free survival in oral (HR[hazard ratio]: 0.94; 95% CI: 0.64–1.39; P = 0.77, HR: 0.94; 95% CI: 0.65–1.36; P = 0.75) and oropharyngeal squamous cell carcinoma (HR: 1.21; 95% CI: 0.81–1.80; P = 0.36, HR: 0.42; 95% CI: 0.79–1.77; P = 0.42). FGFR3 mRNA was upregulated in 3% (18/522) of HNSCC from the TCGA. The FGFR3 gene was gained in 0.6% (1/179) of oral squamous cell carcinoma but no amplification was found in oral and oropharyngeal squamous cell carcinoma. In conclusion, FGFR3 protein is frequently overexpressed in oral and oropharyngeal squamous cell carcinoma. Therefore, it may serve as a potential therapeutic target for FGFR3‐directed therapies in oral and oropharyngeal squamous cell carcinoma.

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Section: Quantitative Reverse Transcription Polymerase Chainmentioning

confidence: 54%

Section: Quantitative Reverse Transcription Polymerase Chainmentioning

confidence: 99%

Fibroblast growth factor receptor 3 protein is overexpressed in oral and oropharyngeal squamous cell carcinoma

et al. 2015

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“…Six papers provided the relative risk (RR), and two articles provided OR values, which we used to estimate HR. Of the 31 studies, a significant association between high Ki-67 expression and poor RFS, PFS, OS and CSS was demonstrated in five [ 22 , 26 , 34 , 35 , 48 ], five [ 31 , 36 , 43 , 46 , 48 ], six [ 20 , 24 , 28 , 29 , 31 , 42 ] and seven studies [ 27 , 30 , 33 , 34 , 42 , 46 , 47 ], respectively. Of the literature, eleven, five, three and two studies linking Ki-67 expression with poor RFS [ 21 , 25 , 37 – 41 , 43 – 45 ], PFS[ 21 , 25 , 41 , 44 , 49 ], OS [ 23 , 32 , 41 ] and CSS [ 43 , 50 ], respectively, lacked statistical significance.…”

Section: Resultsmentioning

confidence: 99%

Clinicopathological and Prognostic Value of Ki-67 Expression in Bladder Cancer: A Systematic Review and Meta-Analysis

Tian

Chen

et al. 2016

PLoS ONE

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BackgroundKi-67 is an established marker of cell proliferation, and the Ki-67 index correlates with the clinical course of several cancer types, including bladder cancer (BC). However, the clinicopathological and prognostic significance of Ki-67 in bladder cancer remains unclear. Therefore, we performed a systematic review and meta-analysis to clarify this relationship.MethodsA comprehensive literature search for relevant studies published up to February 1, 2016, was performed using PubMed, Cochrane Library, Embase and ISI Web of Knowledge. The effects of Ki-67 expression on survival outcome in patients with BC and BC subtypes were evaluated. Furthermore, the relationship between Ki-67 expression and the clinicopathological features of BC were assessed.ResultsThirty-one studies with 5147 bladder cancer patients were selected for evaluation. Ki-67 expression was significantly associated with shorter recurrence-free (HR 1.69, 95% CI: 1.33–2.14), progression-free (HR 1.89, 95% CI: 1.43–2.51), overall (HR 2.03, 95% CI: 1.31–3.16), and cancer-specific (HR 1.69, 95% CI: 1.47–1.95) survival. Moreover, whereas high expression was more common in high tumor stage, recurrence status, tumor size, there was no correlation between high Ki-67 expression and age, gender, smoking habits, and tumor number. Importantly, analysis of the different subgroups of BC suggested that significant correlations between high Ki-67 expression and survival outcome (recurrence-free/progression-free/overall/cancer-specific survival) are present only in European-American patients.ConclusionThe present results indicate that over-expression of Ki-67 is distinctly correlated with poor patient survival. Ki-67 may serve as a valuable biomarker for prognosis in BC patients, particularly in non-Asian BC patients. The results suggest no significant association between Ki-67 expression and BC prognosis in Asian patients. Further efforts are needed to fully clarify this relationship.

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“…Previous studies have investigated the use of FGFR3 expression as a predictor of prognosis in BC. While a number of authors were able to demonstrate a shorter RFS associated with FGFR3 expression ( 20 , 29 ), Gudjonsson et al ( 21 ) did not identify any difference in time to recurrence. In general, the role of molecular markers for predicting BC recurrence appears to be limited, as reviewed by van Rhijn ( 30 ).…”

Section: Discussionmentioning

confidence: 97%

“…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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Expression of Fibroblast Growth Factor Receptor 3 in the Recurrence of Non-Muscle-Invasive Urothelial Carcinoma of the Bladder

Cited by 21 publications

References 26 publications

Fibroblast growth factor receptor 3 protein is overexpressed in oral and oropharyngeal squamous cell carcinoma

Fibroblast growth factor receptor 3 protein is overexpressed in oral and oropharyngeal squamous cell carcinoma

Clinicopathological and Prognostic Value of Ki-67 Expression in Bladder Cancer: A Systematic Review and Meta-Analysis

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

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