Expression of Telomerase Catalytic Subunit (hTERT) mRNA Does Not Predict Survival in Patients with Transitional Cell Carcinoma of the Upper Urinary Tract

Nakanishi, Kuniaki; Hiroi, Sadayuki; Kawai, Toshiaki; Aida, Shinsuke; Kasamatsu, Hiroyasu; Aurues, Takashi; Ikeda, Tomosumi

doi:10.1038/modpathol.3880439

Cited by 15 publications

(8 citation statements)

References 18 publications

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“…There are only a few published reports of the expression of these genes in UTUC. Nakanishi et al [24] showed, in 125 cases of UTUC, no relationship between HTERT and clinicopathological findings, using in situ hybridization. Jeong et al [25] reported, from 112 patients, that BIRC5 expression assessed by immunohistochemistry was a poor prognostic factor for survival in patients with UTUC.…”

Section: Discussionmentioning

confidence: 99%

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Molecular characterization of upper urinary tract tumours

et al. 2010

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transcriptase-polymerase chain reaction (qRT-PCR) in all samples. RESULTSSix genes were over-expressed ( BIRC5, FGFR3, KRT20, UPK2 , FXYD3 and hTERT ) and three under-expressed ( AGR2, TP53 and VEGF ) in the tumour group ( P < 0.05). For four genes ( IGF2, EBF1, CDH1 and HER2 ) there was no statistically significant difference between the tumour and control groups. Overall, 21 patients developed tumour progression and 13 died from UTUC after a mean follow-up of 35.24 months. The 5-year disease-free progression and cancer-specific survival rates were 65.8% and 72.9%, respectively. In a multivariate regression analysis, the independent predictive variable for tumour progression and cancer-specific survival was pathological stage (hazard ratio 3.60, P < 0.001; and 3.73, P < 0.005, respectively), but none of the studied genes were identified as prognostic factors of tumour progression or cancer-specific survival.

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Section: Discussionmentioning

confidence: 99%

“…Nakanishi et al. [24] showed, in 125 cases of UTUC, no relationship between HTERT and clinicopathological findings, using in situ hybridization. Jeong et al.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of upper urinary tract tumours

et al. 2010

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“…To our knowledge, only one previous study has investigated hTERT and PCNA expression in malignancy, that of Nakanishi et al who also found no relationship between the two in urothelial cancers using in situ hybridisation and immunohistochemistry[27]. The correlation between PCNA and telomerase activity has been investigated in gastric carcinoma [28] and cervical intraepithelial neoplasia [29], and again no relationship found.…”

Section: Discussionmentioning

confidence: 99%

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BackgroundTelomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalisation. hTERT (human telomerase reverse transcriptase) is the rate-limiting determinant of telomerase reactivation. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any correlation between hTERT and the negative prognostic indicators VEGF and PCNA by quantitatively measuring the mRNA expression of these genes in human breast cancer and in adjacent non-cancerous tissue (ANCT).Materials and methodsRNA was extracted from 38 breast carcinomas and 40 ANCT. hTERT and VEGF165, VEGF189 and PCNA mRNA expressions were estimated by reverse transcriptase-PCR (RT-PCR) and Taqman methodology.ResultsThe level of expression of VEGF-165 and PCNA was significantly higher in carcinoma tissue than ANCT (p = 0.02). The ratio of VEGF165/189 expression was significantly higher in breast carcinoma than ANCT (p = 0.025). hTERT mRNA expression correlated with VEGF-189 mRNA (p = 0.008) and VEGF165 (p = 0.07).ConclusionshTERT mRNA expression is associated with the expression of the VEGF189 and 165 isoforms. This could explain the poorer prognosis reported in breast tumours expressing high levels of hTERT. The relative expression of the VEGF isoforms is significantly different in breast tumour to ANCT, and this may be important in breast carcinogenesis.

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“…UTUC is less frequent and comprises approximately 5% of urothelial carcinomas [23]. Like other human malignancies, most RCCs and UTUCs exhibit telomerase activation [24,25], which suggests a possibility that TERT promoter mutations occur in these tumors. However, Vinagre et al analyzed 26 RCC tumors including 12 ccRCCs, 4 chRCCs and 10 PRCCs, and did not find any mutation-positive cases [8].…”

Section: Introductionmentioning

confidence: 99%

TERT promoter mutations in renal cell carcinomas and upper tract urothelial carcinomas

Wang

Liu

et al. 2014

Oncotarget

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TERT promoter mutations are identified in many malignancies including bladder cancer (BC) and upper tract urothelial carcinoma (UTUC). In contrast, no mutations were found in renal cell carcinoma (RCC) as reported in a recent study. Because the mutant TERT promoter in urine DNA was recently tested as a marker for BC, it is important to ascertain whether these mutations are truly absent in RCCs. Here we determined TERT promoter mutations in 109 patients with RCC and 14 patients with UTUC. The mutations were found in 9/96 (9.3%) clear cell RCC (ccRCC) tumors and 1/8 (13%) chromophobe RCC tumors. Among ccRCC patients, the mutation was correlated with the advanced stages and metastasis, and higher TERT expression. Among UTUCs, the mutation was detected in tumors from 3/5 (60%) patients with renal pelvic cancer and 1/9 (11%) patients with ureter cancer. The mutation was also detected in 1 of 4 urine samples from patients with mutation+ UTUC. Collectively, TERT promoter mutations do occur in RCCs and are associated with aggressive disease. The mutation is more frequent in renal pelvic cancer. Thus, the mutant TERT promoter found in urine may come from not only BC, but also RCC or UTUC.

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Expression of Telomerase Catalytic Subunit (hTERT) mRNA Does Not Predict Survival in Patients with Transitional Cell Carcinoma of the Upper Urinary Tract

Cited by 15 publications

References 18 publications

Molecular characterization of upper urinary tract tumours

Molecular characterization of upper urinary tract tumours

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TERT promoter mutations in renal cell carcinomas and upper tract urothelial carcinomas

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