Telomerase Activity and Cytokeratin 20 as Markers for the Detection and Followup of Transitional Cell Carcinoma: An Unfulfilled Promise

Cassel, Aliza; Rahat, Michal A.; Lahat, Nitza; Lindenfeld, Noemi; Mecz, Yoel; Stein, Avi

doi:10.1016/s0022-5347(05)65848-x

Cited by 36 publications

(18 citation statements)

References 24 publications

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“…These results are in accord with the fi ndings that this antigen used to be expressed in tumours of epithelial origin with the exception of cervical carcinomas, renal carcinomas, prostate and colon carcinomas (8,9). Cytokeratin 20 was reported to occur in 70-80 % of transitional cell carcinomas (6). In accord with this, we have not found this antigen in 6 out 17 low differentiated carcinomas and in 2 out 12 papillary carcinomas (regardless of the grade of dysplasia), which means 27.5 % of negative UCs.…”

Section: Discussionsupporting

confidence: 89%

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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Section: Discussionsupporting

confidence: 89%

Immunohistochemical characterization of urothelial carcinoma

Rajčáni¹,

Kajo²,

Adamkov³

et al. 2013

BLL

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“…Despite promising preliminary results, diagnostic tests such as telomerase activity detection or cytokeratin 20 have shown to be technically complicated, and their mean sensitivity is no higher than that of urinary cytology (Ramakumar et al, 1999). Moreover, these tests are not specific for malignancy (Cassel et al, 2001;Konety and Getzenberg, 2001). Other assays such as Bard BTA Stat test and NMP22 assay have shown a 67% and 70% sensitivity, respectively, with approximately 70% specificity for both tests (Giannopoulos et al, 2001;Sarosdy et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Improved Detection of Urothelial Carcinomas with Fluorescence Immunocytochemistry (uCyt+ Assay) and Urinary Cytology: Results of a French Prospective Multicenter Study

Piaton

Daniel

Verrièle³

et al. 2003

Laboratory Investigation

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SUMMARY:The aim of the study was to assess the sensitivity and specificity of fluorescence immunocytochemistry (uCytϩ assay) as combined with urinary cytology for detection of primary and recurrent urothelial carcinomas. We analyzed 694 urinary samples from 236 new symptomatic patients and 458 patients followed after transurethral resection (TUR) for bladder tumor. Lesions suspicious for cancer at cystoscopy were sampled by biopsies or TUR. Sensitivity and specificity of tests were calculated using cystoscopy and histopathology, whether or not combined as gold standards. In new symptomatic patients, sensitivity of uCytϩ was 40%, 88.2%, and 76.7%, whereas that of urinary cytology was 30%, 70.6%, and 83.3%, respectively, in G1, G2, and G3 tumors. In follow-up cases, sensitivity of uCytϩ was 61.9%, 66.7%, and 76.9%, whereas that of urinary cytology was 38.1%, 58.3%, and 64.1%, respectively, in G1, G2, and G3 tumors. The combination of uCytϩ and urinary cytology significantly increased mean sensitivity in newly diagnosed cases (86.4% versus 71.2% with urinary cytology only, p Ͻ 0.05), as well as in patients followed after TUR (79.3% versus 55.2%, p Ͻ 0.001). Specificity of uCytϩ and urinary cytology was identical in new patients (83.3%) and was 81.9% and 86.2%, respectively, in patients followed after TUR. In patients with negative cystoscopy, positive uCytϩ tests had a strong predictive value for tumor recurrence at 1 year (47.0% versus 11.9% in patients with negative assay, p Ͻ 0.01). We conclude that combining uCytϩ with urinary cytology improves the detection of urothelial carcinomas as well in patients with symptoms suggesting bladder cancer as in those followed after treatment. (Lab Invest 2003, 83:845-852).

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“…This opinion, ®rst postulated by us as early as 1996 (MuÈ ller et al, 1996) and thereafter controversially discussed in the literature, has, in the meantime, been generally accepted (Arai et al, 2000;Cassel et al, 2001;de Kok et al, 2000a;Wu et al, 2000). Furthermore, the TRAP-assay, despite the assertions of certain authors (Gelmini et al, 2000), is not truly quantitative, but only semiquantitative at best (Yokota et al, 1998) Due to the instability of the enzyme in urine samples and the resulting poor sensitivity of the detection of telomerase activity, alternatives to the TRAP-assay were sought.…”

Section: Urine Samplesmentioning

confidence: 97%

Telomerase: Its clinical relevance in the diagnosis of bladder cancer

Müller

2002

Oncogene

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More than 50 years ago, Papanicolaou recognized the importance of a non-invasive technique for the diagnosis and follow-up of patients with carcinoma of the urinary bladder. Cystoscopy, however, has remained the`gold standard' since no currently available non-invasive method can compete with cystoscopy's sensitivity and speci®city. The detection of the ribonucleoprotein telomerase or the telomerase subunits human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) in urine samples o er new diagnostic perspectives. The present article presents a review of publications in the literature and evaluates their clinical relevance. The experimental studies reported to date are very promising and show that telomerase exactly ful®ls the requirements for a good diagnostic marker for carcinoma of the urinary bladder. The diagnostic application remains in an experimental stage and telomerase is still several steps away for routine use as a clinical parameter. The remaining steps leading to its routine clinical application will be discussed.

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Telomerase Activity and Cytokeratin 20 as Markers for the Detection and Followup of Transitional Cell Carcinoma: An Unfulfilled Promise

Abstract: Telomerase activity and cytokeratin 20 expression are not specific for malignancy and may be detected in many nonmalignant pathological conditions. Therefore, their use as potential markers of bladder carcinoma should be carefully reevaluated.

Cited by 36 publications

References 24 publications

Immunohistochemical characterization of urothelial carcinoma

Immunohistochemical characterization of urothelial carcinoma

Improved Detection of Urothelial Carcinomas with Fluorescence Immunocytochemistry (uCyt+ Assay) and Urinary Cytology: Results of a French Prospective Multicenter Study

Telomerase: Its clinical relevance in the diagnosis of bladder cancer

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