Telomerase reverse transcriptase (TERT) promoter mutation analysis of benign, malignant and reactive urothelial lesions reveals a subpopulation of inverted papilloma with immortalizing genetic change

Liang Cheng, Darrell Davidson, Mingsheng Wang, Antonio Lopez-Beltran, Rodolfo Montironi, Lisha Wang, Puay Hoon Tan, Gregory T. MacLennan, Sean R. Williamson, Shaobo Zhang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Aims: To understand more clearly the genetic ontogeny of inverted papilloma of urinary bladder, we analysed telomerase reverse transcriptase (TERT) promoter mutation status in a group of 26 inverted papillomas in comparison with the mutation status of urothelial carcinoma with inverted growth (26 cases), conventional urothelial carcinoma (36 Ta non-invasive urothelial carcinoma, 35 T2 invasive urothelial carcinoma) and cystitis glandularis (25 cases). Methods and results: TERT promoter mutations in inverted papilloma, urothelial carcinoma with inverted growth, urothelial carcinoma and cystitis glandularis were found in 15% (four of 26), 58% (15 of 26), 63% (45 of 71) and 0% (none of 25), respectively. C228T mutations were the predominant mutations (97%) found in bladder tumours, while C250T aberrations occurred in approximately 3% of bladder tumours. In the inverted papilloma group, TERT mutation occurred predominantly in female patients (P = 0.006). Among urothelial carcinomas, TERT promoter mutation status did not correlate with gender, histological grade or pathological stage. Conclusions: TERT promoter mutations were found in 15% of inverted papillomas. Our data suggest that there is a subpopulation of inverted papilloma that shares a carcinogenetic pathway with urothelial carcinoma with inverted growth and conventional urothelial carcinomas. Caution is warranted in exploring TERT promoter mutation status as a screening or adjunct diagnostic test for bladder cancer.

Original languageEnglish (US)
Pages (from-to)107-113
Number of pages7
JournalHistopathology
Volume69
Issue number1
DOIs
StatePublished - Jul 1 2016

Fingerprint

Inverted Papilloma
Telomerase
Carcinoma
Mutation
Urinary Bladder Neoplasms
Cystitis
Growth
Routine Diagnostic Tests
Urinary Bladder

Keywords

  • carcinogenesis
  • differential diagnosis
  • inverted papilloma
  • inverted urothelial carcinoma
  • molecular genetics
  • TERT promoter mutation
  • urinary bladder

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

Telomerase reverse transcriptase (TERT) promoter mutation analysis of benign, malignant and reactive urothelial lesions reveals a subpopulation of inverted papilloma with immortalizing genetic change. / Cheng, Liang; Davidson, Darrell; Wang, Mingsheng; Lopez-Beltran, Antonio; Montironi, Rodolfo; Wang, Lisha; Tan, Puay Hoon; MacLennan, Gregory T.; Williamson, Sean R.; Zhang, Shaobo.

In: Histopathology, Vol. 69, No. 1, 01.07.2016, p. 107-113.

Research output: Contribution to journalArticle

Cheng, Liang ; Davidson, Darrell ; Wang, Mingsheng ; Lopez-Beltran, Antonio ; Montironi, Rodolfo ; Wang, Lisha ; Tan, Puay Hoon ; MacLennan, Gregory T. ; Williamson, Sean R. ; Zhang, Shaobo. / Telomerase reverse transcriptase (TERT) promoter mutation analysis of benign, malignant and reactive urothelial lesions reveals a subpopulation of inverted papilloma with immortalizing genetic change. In: Histopathology. 2016 ; Vol. 69, No. 1. pp. 107-113.
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abstract = "Aims: To understand more clearly the genetic ontogeny of inverted papilloma of urinary bladder, we analysed telomerase reverse transcriptase (TERT) promoter mutation status in a group of 26 inverted papillomas in comparison with the mutation status of urothelial carcinoma with inverted growth (26 cases), conventional urothelial carcinoma (36 Ta non-invasive urothelial carcinoma, 35 T2 invasive urothelial carcinoma) and cystitis glandularis (25 cases). Methods and results: TERT promoter mutations in inverted papilloma, urothelial carcinoma with inverted growth, urothelial carcinoma and cystitis glandularis were found in 15{\%} (four of 26), 58{\%} (15 of 26), 63{\%} (45 of 71) and 0{\%} (none of 25), respectively. C228T mutations were the predominant mutations (97{\%}) found in bladder tumours, while C250T aberrations occurred in approximately 3{\%} of bladder tumours. In the inverted papilloma group, TERT mutation occurred predominantly in female patients (P = 0.006). Among urothelial carcinomas, TERT promoter mutation status did not correlate with gender, histological grade or pathological stage. Conclusions: TERT promoter mutations were found in 15{\%} of inverted papillomas. Our data suggest that there is a subpopulation of inverted papilloma that shares a carcinogenetic pathway with urothelial carcinoma with inverted growth and conventional urothelial carcinomas. Caution is warranted in exploring TERT promoter mutation status as a screening or adjunct diagnostic test for bladder cancer.",
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AU - Cheng, Liang

AU - Davidson, Darrell

AU - Wang, Mingsheng

AU - Lopez-Beltran, Antonio

AU - Montironi, Rodolfo

AU - Wang, Lisha

AU - Tan, Puay Hoon

AU - MacLennan, Gregory T.

AU - Williamson, Sean R.

AU - Zhang, Shaobo

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Aims: To understand more clearly the genetic ontogeny of inverted papilloma of urinary bladder, we analysed telomerase reverse transcriptase (TERT) promoter mutation status in a group of 26 inverted papillomas in comparison with the mutation status of urothelial carcinoma with inverted growth (26 cases), conventional urothelial carcinoma (36 Ta non-invasive urothelial carcinoma, 35 T2 invasive urothelial carcinoma) and cystitis glandularis (25 cases). Methods and results: TERT promoter mutations in inverted papilloma, urothelial carcinoma with inverted growth, urothelial carcinoma and cystitis glandularis were found in 15% (four of 26), 58% (15 of 26), 63% (45 of 71) and 0% (none of 25), respectively. C228T mutations were the predominant mutations (97%) found in bladder tumours, while C250T aberrations occurred in approximately 3% of bladder tumours. In the inverted papilloma group, TERT mutation occurred predominantly in female patients (P = 0.006). Among urothelial carcinomas, TERT promoter mutation status did not correlate with gender, histological grade or pathological stage. Conclusions: TERT promoter mutations were found in 15% of inverted papillomas. Our data suggest that there is a subpopulation of inverted papilloma that shares a carcinogenetic pathway with urothelial carcinoma with inverted growth and conventional urothelial carcinomas. Caution is warranted in exploring TERT promoter mutation status as a screening or adjunct diagnostic test for bladder cancer.

AB - Aims: To understand more clearly the genetic ontogeny of inverted papilloma of urinary bladder, we analysed telomerase reverse transcriptase (TERT) promoter mutation status in a group of 26 inverted papillomas in comparison with the mutation status of urothelial carcinoma with inverted growth (26 cases), conventional urothelial carcinoma (36 Ta non-invasive urothelial carcinoma, 35 T2 invasive urothelial carcinoma) and cystitis glandularis (25 cases). Methods and results: TERT promoter mutations in inverted papilloma, urothelial carcinoma with inverted growth, urothelial carcinoma and cystitis glandularis were found in 15% (four of 26), 58% (15 of 26), 63% (45 of 71) and 0% (none of 25), respectively. C228T mutations were the predominant mutations (97%) found in bladder tumours, while C250T aberrations occurred in approximately 3% of bladder tumours. In the inverted papilloma group, TERT mutation occurred predominantly in female patients (P = 0.006). Among urothelial carcinomas, TERT promoter mutation status did not correlate with gender, histological grade or pathological stage. Conclusions: TERT promoter mutations were found in 15% of inverted papillomas. Our data suggest that there is a subpopulation of inverted papilloma that shares a carcinogenetic pathway with urothelial carcinoma with inverted growth and conventional urothelial carcinomas. Caution is warranted in exploring TERT promoter mutation status as a screening or adjunct diagnostic test for bladder cancer.

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KW - differential diagnosis

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KW - inverted urothelial carcinoma

KW - molecular genetics

KW - TERT promoter mutation

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