Non-Invasive Papillary Carcinoma of the Bladder Associated with Carcinoma in Situ

Althausen, Alex F.; Prout, George R.; Daly, James J.

doi:10.1016/s0022-5347(17)58916-8

Cited by 429 publications

(127 citation statements)

References 25 publications

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“…Urothelial dysplasia is an incidental microscopic finding where urothelial cells show mild atypical features short of the diagnosis of carcinoma in situ. It is considered a precancerous process, and studies have shown that up to 19% of urothelial dysplasia cases develop urothelial carcinoma (22)(23)(24). Although precancerous, it is recommended that patients with dysplasia receive proper clinical follow-up for early detection of an imminent carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo

Golijanin

Amin

Moshnikova

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.bladder cancer | fluorescence-guided surgery | NIR imaging | acidity | human tissue

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Section: Discussionmentioning

confidence: 99%

Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo

Golijanin

Amin

Moshnikova

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…2). The patients presenting with isolated or concomitant CIS lesions have a high risk of disease progression to a muscle invasive stage (3). The CIS lesions may have a widespread manifestation in the bladder (field disease) and are believed to be the most common precursors of invasive carcinomas (4,5).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression in the Urinary Bladder

et al. 2004

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The presence of carcinoma in situ (CIS) lesions in the urinary bladder is associated with a high risk of disease progression to a muscle invasive stage. In this study, we used microarray expression profiling to examine the gene expression patterns in superficial transitional cell carcinoma (sTCC) with surrounding CIS (13 patients), without surrounding CIS lesions (15 patients), and in muscle invasive carcinomas (mTCC; 13 patients). Hierarchical cluster analysis separated the sTCC samples according to the presence or absence of CIS in the surrounding urothelium. We identified a few gene clusters that contained genes with similar expression levels in transitional cell carcinoma (TCC) with surrounding CIS and invasive TCC. However, no close relationship between TCC with adjacent CIS and invasive TCC was observed using hierarchical cluster analysis. Expression profiling of a series of biopsies from normal urothelium and urothelium with CIS lesions from the same urinary bladder revealed that the gene expression found in sTCC with surrounding CIS is found also in CIS biopsies as well as in histologically normal samples adjacent to the CIS lesions. Furthermore, we also identified similar gene expression changes in mTCC samples. We used a supervised learning approach to build a 16-gene molecular CIS classifier. The classifier was able to classify sTCC samples according to the presence or absence of surrounding CIS with a high accuracy. This study demonstrates that a CIS gene expression signature is present not only in CIS biopsies but also in sTCC, mTCC, and, remarkably, in histologically normal urothelium from bladders with CIS. Identification of this expression signature could provide guidance for the selection of therapy and follow-up regimen in patients with early stage bladder cancer.

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“…Despite the fact that the majority of superficial bladder tumors are clinically benign, regular cystoscopic follow-up at intervals is done in all patients with noninvasive bladder cancer after complete transurethral resection to detect recurrence and progression. A plethora of potential clinical and histopathologic factors indicative of tumor progression are currently discussed in the context of papillary bladder cancer: high tumor grade (2), tumor size of >5 cm (3), multifocality (4), adjacent carcinoma in situ (5), and high rate of recurrence. However, none of these markers reliably predicts a higher progression rate in papillary carcinoma of the bladder (pTa).…”

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confidence: 99%

Gene Expression Profiling of Progressive Papillary Noninvasive Carcinomas of the Urinary Bladder

Wild

Herr²,

Wissmann³

et al. 2005

Clinical Cancer Research

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Purpose:The aim of the present study was to define gene expression profiles of noninvasive and invasive bladder cancer, to identify potential therapeutic or screening targets in bladder cancer, and to define genetic changes relevant for tumor progression of recurrent papillary bladder cancer (pTa). Experimental Design: Overall, 67 bladder neoplasms (46 pTa, 3 pTis, 10 pT1, and 8 pT2) and eight normal bladder specimens were investigated by a combination of laser microdissection and gene expression profiling. Eight of 16 patients with recurrent noninvasive papillary bladder tumors developed carcinoma in situ (pTis) or invasive bladder cancer (zpT1G2) in the course of time. RNA expression results of the putative progression marker cathepsin E (CTSE) were confirmed by immunohistochemistry using high-throughput tissue microarray analysis (n = 776). Univariate analysis of factors regarding overall survival, progression-free survival, and recurrence-free survival in patients with urothelial bladder cancer was done. Results: Hierarchical cluster analyses revealed no differences between pTaG1 and pTaG2 tumors. However, distinct groups of invasive cancers with different gene expression profiles in papillary and solid tumors were found. Progression-associated gene profiles could be defined (e.g., FABP4 and CTSE) and were already present in the preceding noninvasive papillary tumors. CTSE expression (P = 0.003) and a high Ki-67 labeling index of at least 5% (P = 0.01) were the only factors that correlated significantly with progression-free survival of pTa tumors in our gene expression approach. Conclusions: Gene expression profiling revealed novel genes with potential clinical utility to select patients that are more likely to develop aggressive disease.At the time of first diagnosis, f70% of bladder tumors are noninvasive papillary low-grade tumors (pTa). However, >60% of these tumors will recur at least once and progress to infiltrating or less differentiated neoplasms in 5% to 10% of cases (1). Despite the fact that the majority of superficial bladder tumors are clinically benign, regular cystoscopic follow-up at intervals is done in all patients with noninvasive bladder cancer after complete transurethral resection to detect recurrence and progression. A plethora of potential clinical and histopathologic factors indicative of tumor progression are currently discussed in the context of papillary bladder cancer: high tumor grade (2), tumor size of >5 cm (3), multifocality (4), adjacent carcinoma in situ (5), and high rate of recurrence. However, none of these markers reliably predicts a higher progression rate in papillary carcinoma of the bladder (pTa). It is important to identify the small subgroup of patients that will most likely benefit from close clinical follow-up and Bacillus Calmette-Guerin instillation therapy. New molecular prognostic markers for the prediction of tumor recurrence and progression are urgently needed.Mutations of the tumor suppressor genes TP53 and RB1 are common and have predictive va...

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Non-Invasive Papillary Carcinoma of the Bladder Associated with Carcinoma in Situ

Cited by 429 publications

References 25 publications

Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo

Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo

Gene Expression in the Urinary Bladder

Gene Expression Profiling of Progressive Papillary Noninvasive Carcinomas of the Urinary Bladder

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