Microstaging of pT1 transitional cell carcinoma of the bladder: identification of subgroups with distinct risks of progression

Smits, G.A.H.J.; Schaafsma, Ewout; Kiemeney, Lambertus A.; Caris, Christien; Debruyne, F.M.J.; Witjes, J. Alfred

doi:10.1016/s0090-4295(98)00374-4

Cited by 110 publications

(75 citation statements)

References 15 publications

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“…Depth of invasion within the subepithelial connective tissue in the TUR specimen has a prognostic value with respect to the risk of tumour progression [6,7,8,16,17,18,19,20,21,22]. A distinctive prognosis can be expected for tumours with different levels of invasion [4].…”

Section: Discussionmentioning

confidence: 99%

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The Prognostic Value of T1 Bladder Cancer Substaging: A Single Institution Retrospective Study

Soukup¹,

Dušková

Pešl³

et al. 2014

Urol Int

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Objective: To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer. Subjects and Methods: 200 patients were treated between the years 2002 and 2009. Tumours with depth of invasion above the muscularis mucosae level were categorised as pT1a and those with depth of invasion up to or beyond the muscularis mucosae as pT1b. Results: Categorisation for pT1a and pT1b was performed in 176 of 200 patients (88%). In 10 patients a muscle-invasive tumour was found in re-transurethral resection samples. 131 (79%) of 166 analysed patients had pT1a tumour and 35 (21%) had pT1b tumour. During the follow-up, in 101 (61%) patients the tumour had recurred and in 27 (16.3%) the tumour had progressed. Of all the investigated parameters, T1 substaging (p < 0.0001), grade (p = 0.0003) and the number of bacillus Calmette-Guérin instillations (p = 0.0490) were significant in predicting progression. The only significant factor for disease-specific survival was T1 substaging in univariable (p = 0.0008) and multivariable (hazard ratio 4.407) analysis. T1 substaging (p = 0.0149) and tumour multiplicity (p = 0.0448) have a statistically significant prognostic value with respect to overall survival. Conclusions: Deep invasion of the lamina propria is a significant adverse prognostic factor for tumour progression, disease-specific survival and overall survival.

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Section: Discussionmentioning

confidence: 99%

“…Invasion depth of the lamina propria has been associated with an increased risk of disease progression and death [5,6,7,8,9]. Despite this fact, T1 bladder cancer substaging has not been recommended in either clinical guidelines or classification systems for stages [10,11].…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Value of T1 Bladder Cancer Substaging: A Single Institution Retrospective Study

Soukup¹,

Dušková

Pešl³

et al. 2014

Urol Int

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“…The matter of controversy is the essentially non-invasive HG UCs, clinically pT1 grade, which shows endophytic growth of various extent into the lamina propria. Some authors claimed that the depth of endophytic growth into the subepithelial connective tissue might be of prognostic importance; they suggested to classify the pT1 tumours into the stages pT1a and pT1b (12,61). Nevertheless, this subdivision has not been widely accepted.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical characterization of urothelial carcinoma

Rajčáni¹,

Kajo²,

Adamkov³

et al. 2013

BLL

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From the archive of BB Biocyt company, 32 urinary bladder carcinomas (urothelium carcinomas, UC) and 7 cases of chronic cystitis were selected and examined in semiserial sections for the following antigens: 1) cell proliferation marker Ki-67 (expressed in the nuclei), 2) cell cycle regulator p16/INK4a polypeptide (expressed in the cytoplasm and nuclei), 3) urothelium marker p63 (expressed in the nuclei), 4) cytokeratin 7 (CK7). 5) cytokeratin 20 (CK20) and 6) high molecular weight cytokeratin (HMWCK). Invasive urothelium carcinomas showing a high grade dysplasia (invasive HG UC) comprised over the half (20 out of 32) of the investigated tumours. Microinvasion to lamina propria (seen in three HG papillary carcinomas) was regarded as an early infi ltration even when the position of muscular layer could not be determined. Classical invasion across the urinary bladder wall and/or to surrounding tissues was found in 17 cases of low-differentiated HG UCs. The rest (9 out of 32 neoplasms) were either non-invasive papillary carcinomas of high (non-invasive HG UC, 5 cases) or low malignant potential (noninvasive LG UC, 4 cases). Finally, 3 cases were papillary urothelium neoplasms of low malignant potential (PUNLMP). HMWCK was present in all invasive tumours, whereas the frequency of other urothelium markers ranged from 65 to 88 %. Nevertheless, at least two markers were expressed in each invasive tumour. Staining for Ki-67 antigen was positive in over 50 % of the nuclei of HG UCs, while in the LG UCs, the frequency of positive Ki-67 staining did not exceed 25 %. In PUNLMP, the positive rate of Ki-67 stained dysplastic cells was below 10 %. The staining for p16 antigen did not correlate with the degree of dysplasia within urothelium tumours. For routine diagnostic, we recommend to combine the Ki-67 staining with detection of HMWCK. In cases of chronic cystitis, which developed urothelial hyperplasia and/or squamous metaplasia, the presence of p63 antigen was a relevant marker confi rming the urothelial origin of the altered transitional cells (Tab. 6, Fig. 4, Ref. 69)

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“…The data show that the extent of lamina propria invasion is a clinically relevant prognostic factor for progression of pT1 TCC of the bladder (Smits et al, 1998;Younes et al, 1990). Tumors extending beyond the muscularis mucosa behave in a way similar to muscle-invasive TCC, especially if they are high-grade, reveal associated carcinoma in situ, or express nuclear TP53 (Hermann et al, 1998;Smits et al, 1998;Younes et al, 1990).…”

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confidence: 86%

Molecular Evolution and Intratumor Heterogeneity by Topographic Compartments in Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder

Díaz‐Cano

Blanes²,

Rubio³

et al. 2000

Laboratory Investigation

122

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SUMMARY:Superficial transitional cell carcinomas (TCC) of the urinary bladder have been shown to be monoclonal. However, no combined study of clonality and tumor suppressor genes (TSG) is available to date for muscle-invasive TCC. Forty-four muscle-invasive TCC of the urinary bladder selected from women were included in this study. Tumor cells located above and below the muscularis mucosa zone were systematically microdissected and used for DNA extraction. Hha-I digested and undigested samples were used to study the methylation pattern of androgen receptor alleles and undigested samples were used for microsatellite analysis of TSG (TP53, RB1, WT1, and NF1). Both loss of heterozygosity (LOH) and single nucleotide polymorphism (SNP) analyses were performed using optimized denaturing gradient gel electrophoresis. The expression of p53, pRB, and p21 WAF1 was assessed by immunohistochemistry. Appropriate controls were run in every case. All except two TCC showed a monoclonal pattern with the same allele inactivated in both compartments. Microsatellite analysis of TSG revealed the same LOH/SNP pattern in both tumor compartments in 30 cases (involving more than 1 TSG locus in 8) and genetic heterogeneity in 14 cases. From the latter group, 9 cases expressed more genetic changes in the deep compartment (involving TP53 gene in all cases, WT1 gene in 2, and NF1 in 1), whereas in 4 cases the superficial compartment showed more genetic changes (three involving NF1 and one involving both RB and TP53). No statistical difference in the immunoexpression was detected, although it tended to be higher in the superficial compartment than in the deep compartment. These concordant data in polymorphic DNA regions indicate that bladder-muscle-invasive TCC are monoclonal proliferations with homogeneous tumor cell selection. Heterogeneous tumor cell selection by topography defined two different genetic compartments: superficial, NF1-defective, and deep, TP53-defective. No differences in the immunohistochemical expression were observed, precluding a more extensive clinical application. (Lab Invest 2000, 80:279-289).

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Microstaging of pT1 transitional cell carcinoma of the bladder: identification of subgroups with distinct risks of progression

Cited by 110 publications

References 15 publications

The Prognostic Value of T1 Bladder Cancer Substaging: A Single Institution Retrospective Study

The Prognostic Value of T1 Bladder Cancer Substaging: A Single Institution Retrospective Study

Immunohistochemical characterization of urothelial carcinoma

Molecular Evolution and Intratumor Heterogeneity by Topographic Compartments in Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder

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