Molecular Grading of Urothelial Cell Carcinoma With Fibroblast Growth Factor Receptor 3 and MIB-1 is Superior to Pathologic Grade for the Prediction of Clinical Outcome

Rhijn, Bas W.G. van; Vis, André N.; Kwast, Theodorus H. van der; Kirkels, Wim J.; Radvanyi, François; Ooms, E. C. M.; Chopin, Dominique; Boevé, Egbert R.; Jöbsis, A. C.; Zwarthoff, Ellen C.

doi:10.1200/jco.2003.05.073

Cited by 288 publications

(235 citation statements)

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“…As FGFR3 is a gene involved in bladder carcinogenesis and the presence of FGFR3 mutations is also a common event in benign skin tumors, [30][31][32]35,37,41 this association between bladder, skin, and prostate cancer could suggest a common role for FGFR3 in their pathogenesis. However, the mutational analysis of the corresponding bladder tumors and normal prostate samples in some of the patients from our study revealed the wild-type status of the gene.…”

Section: Discussionmentioning

confidence: 99%

“…37 To test the possibility of finding exon 15 mutations in prostate cancer we screened a subgroup of 53 tumors, classified as grade The F386L germline single nucleotide polymorphism (SNP) was detected in two samples (2%), both of them from radical prostatectomy tumors with a combined Gleason score ¼ 7 ( Table 2). The prevalence of this polymorphism in heterozygosity is about 1% (http://www.ncbi.nlm.nih.gov/SNP).…”

Section: Fgfr3 Mutation Analysismentioning

confidence: 99%

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FGFR3 mutations in prostate cancer: association with low-grade tumors

et al. 2009

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Prostate cancer is the second cause of cancer-related death in men of the Western World. The role of FGFR3 and its abnormalities in prostate cancer are not known. FGFR3 mutations have been reported in some human tumors. Few studies have analyzed the mutations of FGFR3 in prostate tumors, and no mutations have been previously reported. Prevalence of FGFR3 somatic mutations was investigated in a series of prostate tumors. The presence of other tumors in these patients, including urothelial, skin, colon, and lung neoplasms, was recorded. Mutational analysis of exons 7, 10, and 15 of FGFR3 revealed 9 mutations in the 112 prostate tumors studied (8%). Most of them consisted of the missense change S249C. The prevalence of mutations in tumors with combined Gleason score ¼ 6 is 18% (8/45) compared to 3% (1/36) for tumors with grade ¼ 7, and 0% (0/31) for those with grade Z8 and metastases (P ¼ 0.007). The frequency of FGFR3 mutations in autopsy and biopsy samples was 6 and 9%, respectively. The prevalence of FGFR3 mutations in prostate tumors from patients with only prostate cancer was 2% compared to 23% in prostate tumors from patients with other associated neoplasms (P ¼ 0.001). This is the first report of molecular changes of FGFR3 in prostate cancer. This gene does not seem to be central to the pathogenesis of prostate cancer, but it is significantly associated with a subgroup of low-grade prostate tumors, and with the finding of other tumors, mainly arising in bladder and skin.

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Section: Discussionmentioning

confidence: 99%

Section: Fgfr3 Mutation Analysismentioning

confidence: 99%

FGFR3 mutations in prostate cancer: association with low-grade tumors

et al. 2009

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“…Although a small percentage of invasive carcinomas are low grade, usually limited to the lamina propria, >95% of Admittedly, controversy remains, and the reasons are multifactorial but mainly due to the fact that the clinical risk of recurrence and progression are determined not solely by growth pattern and grade but also by other factors such as size, multifocality, time to recurrence, and prior intravesical therapy. In addition, we must accept the fact that grading is largely subjective and that, in the future, ancillary studies (either immunohistochemical or molecular assays) will lead to enhanced reproducibility and better correlation with clinical outcome [52].…”

Section: Grading Of Urothelial Tumoursmentioning

confidence: 99%

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

et al. 2016

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It has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours. Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 WHO classification. In most cases, it represents intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia. New acinar adenocarcinoma variants are microcystic adenocarcinoma and pleomorphic giant cell adenocarcinoma. Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7. The new WHO classification further recommends the recently developed prostate cancer grade grouping with five grade groups. For bladder cancer, the 2016 WHO classification continues to recommend the 1997 International Society of Urological Pathology grading classification. Newly described or better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential, which is frequently identified in patients with a prior history of urothelial carcinoma. Invasive urothelial carcinoma with divergent differentiation refers to tumours with some percentage of "usual type" urothelial carcinoma combined with other morphologies. Pathologists should mention the percentage of divergent histologies in the pathology report. PATIENT SUMMARY Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 World Health Organization classification. Better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential. v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j AbstractIt has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours.

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“…[7][8][9][10][11][12] Also, molecular grading of UCC showed improved predictive potential compared to classical pathological parameters. 13 Despite these advances, no molecular marker is integrated in clinical prognostics yet.In the ongoing search for recurrence-predictive markers, several studies have attempted to molecularly classify bladder tumors by cDNA microarray analysis. 14-18 One of these studies identified a panel of 26 genes, which distinguished between early-recurring and nonrecurring superficial Ta tumors in a cohort of 31 patients.…”

mentioning

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Prediction of recurrence in Ta urothelial cell carcinoma by real‐time quantitative PCR analysis: A microarray validation study

Schultz

Wester

Straatman

et al. 2006

Intl Journal of Cancer

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Accurate prediction of tumor recurrence in patients with superficial urothelial cell carcinoma (UCC) might result in a significant reduction of invasive follow-up cystoscopies. A recent study identified a panel of 26 genes from a large cDNA microarray analysis of bladder tumors that discriminated between early-and late-recurring patients with superficial Ta tumors (Dyrskjøt et al., Nat Genet 2003;33:90-6). We aimed to validate this panel of genes in 44 primary Ta UCCs (23 and 21 tumors from patients with short or prolonged recurrence-free periods, respectively), by real-time quantitative PCR. Statistical analysis showed marginal significant different mRNA expression levels between the 2 patient groups. To evaluate a supplementary effect of genes for the identification of patients with short or prolonged recurrence-free intervals, forward logistic regression analysis was applied. This revealed that a combination of the expression profiles of the genes HNRPK, LTB4DH and ANP32B resulted in the best performance, although the combination only marginally increased the predictive value of HNRPK alone. Comparing the receiver-operating-characteristic curves for HNRPK expression among patients with short or prolonged recurrence-free periods, revealed an area under the curve of 0.696 (95% CI, 0.537-0.855). Using the median HNRPK expression level as cut-off, a sensitivity of 69.6% and a specificity of 71.4% were obtained for the identification of patients with short or prolonged recurrence-free periods, respectively. In conclusion, we were not able to confirm the microarray gene expression pattern of the 26 genes shown by Dyrskjøt et al. The discovery of accurate recurrence predictive markers, therefore, remains a challenge. ' 2006 Wiley-Liss, Inc.Key words: recurrence; urothelial cell carcinoma; real-time quantitative PCR; microarray; validation Urothelial cell carcinoma (UCC) comprises up to 95% of human bladder cancer. It originates in the urothelium, the layer of cells lining the inner bladder wall. The larger part of patients with UCC is diagnosed with superficial tumors, pTNM stages Ta and T1, of which the depth of organ invasion is limited to the stromal mucosa. These tumors can be removed relatively easy by transurethral resection. Unfortunately, 70% of these patients experience recurrences after tumor removal and some will show progression towards muscle invasive disease. This necessitates frequent examination of the bladder by cystoscopy, which is invasive and represents a burden to the patient. The monitoring of these patients also includes those who will remain recurrence-free for several years or even for the rest of their lives. This generates a substantial number of unnecessary cystoscopies, which may be prevented by accurate prediction of tumor recurrence (or nonrecurrence) in patients with superficial UCC.The current standards for the estimation of the risk of recurrence are tumor grade, size and multiplicity. 1-3 Although these factors are relatively accurate in the group of patients with superficial UCC,...

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Molecular Grading of Urothelial Cell Carcinoma With Fibroblast Growth Factor Receptor 3 and MIB-1 is Superior to Pathologic Grade for the Prediction of Clinical Outcome

Abstract: The FGFR3 mutation represents the favorable molecular pathway of UCC. Molecular grading provides a new, simple, and highly reproducible tool for clinical decision making in UCC patients.

Cited by 288 publications

References 38 publications

FGFR3 mutations in prostate cancer: association with low-grade tumors

FGFR3 mutations in prostate cancer: association with low-grade tumors

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

Prediction of recurrence in Ta urothelial cell carcinoma by real‐time quantitative PCR analysis: A microarray validation study

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