Micropapillary urothelial carcinoma of urinary bladder displays immunophenotypic features of luminal and p53-like subtypes and is not a variant of adenocarcinoma

Yu Yang, Hristos Z. Kaimakliotis, Sean R. Williamson, Michael O. Koch, Kun Huang, Marcelo P. Barboza, Shaobo Zhang, Mingsheng Wang, Muhammad T. Idrees, David J. Grignon, John N. Eble, Lee Ann Baldridge, Liang Cheng

Research output: Contribution to journalArticle

Abstract

Objectives: Micropapillary urothelial carcinoma of the urinary bladder (MPUC) is a rare variant of urothelial carcinoma which has aggressive clinical characteristics. The objective is to investigate the molecular subtypes of MPUC and the impact to the clinical outcome and determine whether MPUC represents a variant of adenocarcinoma. Materials and Methods: We evaluated surrogate immunohistochemical markers of luminal, basal, and p53-like subtypes and correlated with prognosis and the expression of markers related to bladder adenocarcinoma and glandular differentiation in 56 cases of MPUC (10 cases of transurethral resection and 46 cases of radical cystectomy). Biomarker expression in co-existing conventional urothelial carcinoma was also analyzed. Cox regression analysis was performed to study the impact of molecular subtype on the clinical outcome. Results: Thirty-four cases (61%) met criteria for the luminal subtype. Twenty-two cases (39%) displayed a p53-like subtype. In contrast, 40/56 (71%) cases of coexisting conventional urothelial carcinoma were classified as luminal subtype and 16/56 (29%) cases were designated as p53-like subtype. There was no significant survival difference between luminal subtype and p53-like subtype. CDX2, villin, and cadherin 17 were negative in all cases. MUC1 was strongly and diffusely expressed in the stroma-facing surface of MPUC tumor cells in all the cases. Conclusions: Our findings suggest that MPUC possesses characteristics of luminal and p53-like subtypes, and does not harbor phenotypic features of the basal subtype. There is no significant difference in the prognosis between luminal and p53-like subtype MPUC. MPUC is not a variant of adenocarcinoma and does not represent a form of glandular differentiation, in contrast to other organ sites.

Original languageEnglish (US)
JournalUrologic Oncology: Seminars and Original Investigations
DOIs
StateAccepted/In press - Jan 1 2019

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Urinary Bladder
Adenocarcinoma
Carcinoma
Biomarkers
Cystectomy
Cadherins
Regression Analysis
Neoplasms

Keywords

  • Basal/luminal subtype
  • Micropapillary variant
  • Molecular classification
  • Molecular genetics
  • Urinary bladder

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

@article{d247148a564f4cdda3fa691072395d0f,
title = "Micropapillary urothelial carcinoma of urinary bladder displays immunophenotypic features of luminal and p53-like subtypes and is not a variant of adenocarcinoma",
abstract = "Objectives: Micropapillary urothelial carcinoma of the urinary bladder (MPUC) is a rare variant of urothelial carcinoma which has aggressive clinical characteristics. The objective is to investigate the molecular subtypes of MPUC and the impact to the clinical outcome and determine whether MPUC represents a variant of adenocarcinoma. Materials and Methods: We evaluated surrogate immunohistochemical markers of luminal, basal, and p53-like subtypes and correlated with prognosis and the expression of markers related to bladder adenocarcinoma and glandular differentiation in 56 cases of MPUC (10 cases of transurethral resection and 46 cases of radical cystectomy). Biomarker expression in co-existing conventional urothelial carcinoma was also analyzed. Cox regression analysis was performed to study the impact of molecular subtype on the clinical outcome. Results: Thirty-four cases (61{\%}) met criteria for the luminal subtype. Twenty-two cases (39{\%}) displayed a p53-like subtype. In contrast, 40/56 (71{\%}) cases of coexisting conventional urothelial carcinoma were classified as luminal subtype and 16/56 (29{\%}) cases were designated as p53-like subtype. There was no significant survival difference between luminal subtype and p53-like subtype. CDX2, villin, and cadherin 17 were negative in all cases. MUC1 was strongly and diffusely expressed in the stroma-facing surface of MPUC tumor cells in all the cases. Conclusions: Our findings suggest that MPUC possesses characteristics of luminal and p53-like subtypes, and does not harbor phenotypic features of the basal subtype. There is no significant difference in the prognosis between luminal and p53-like subtype MPUC. MPUC is not a variant of adenocarcinoma and does not represent a form of glandular differentiation, in contrast to other organ sites.",
keywords = "Basal/luminal subtype, Micropapillary variant, Molecular classification, Molecular genetics, Urinary bladder",
author = "Yu Yang and Kaimakliotis, {Hristos Z.} and Williamson, {Sean R.} and Koch, {Michael O.} and Kun Huang and Barboza, {Marcelo P.} and Shaobo Zhang and Mingsheng Wang and Idrees, {Muhammad T.} and Grignon, {David J.} and Eble, {John N.} and Baldridge, {Lee Ann} and Liang Cheng",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.urolonc.2019.10.013",
language = "English (US)",
journal = "Urologic Oncology",
issn = "1078-1439",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Micropapillary urothelial carcinoma of urinary bladder displays immunophenotypic features of luminal and p53-like subtypes and is not a variant of adenocarcinoma

AU - Yang, Yu

AU - Kaimakliotis, Hristos Z.

AU - Williamson, Sean R.

AU - Koch, Michael O.

AU - Huang, Kun

AU - Barboza, Marcelo P.

AU - Zhang, Shaobo

AU - Wang, Mingsheng

AU - Idrees, Muhammad T.

AU - Grignon, David J.

AU - Eble, John N.

AU - Baldridge, Lee Ann

AU - Cheng, Liang

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objectives: Micropapillary urothelial carcinoma of the urinary bladder (MPUC) is a rare variant of urothelial carcinoma which has aggressive clinical characteristics. The objective is to investigate the molecular subtypes of MPUC and the impact to the clinical outcome and determine whether MPUC represents a variant of adenocarcinoma. Materials and Methods: We evaluated surrogate immunohistochemical markers of luminal, basal, and p53-like subtypes and correlated with prognosis and the expression of markers related to bladder adenocarcinoma and glandular differentiation in 56 cases of MPUC (10 cases of transurethral resection and 46 cases of radical cystectomy). Biomarker expression in co-existing conventional urothelial carcinoma was also analyzed. Cox regression analysis was performed to study the impact of molecular subtype on the clinical outcome. Results: Thirty-four cases (61%) met criteria for the luminal subtype. Twenty-two cases (39%) displayed a p53-like subtype. In contrast, 40/56 (71%) cases of coexisting conventional urothelial carcinoma were classified as luminal subtype and 16/56 (29%) cases were designated as p53-like subtype. There was no significant survival difference between luminal subtype and p53-like subtype. CDX2, villin, and cadherin 17 were negative in all cases. MUC1 was strongly and diffusely expressed in the stroma-facing surface of MPUC tumor cells in all the cases. Conclusions: Our findings suggest that MPUC possesses characteristics of luminal and p53-like subtypes, and does not harbor phenotypic features of the basal subtype. There is no significant difference in the prognosis between luminal and p53-like subtype MPUC. MPUC is not a variant of adenocarcinoma and does not represent a form of glandular differentiation, in contrast to other organ sites.

AB - Objectives: Micropapillary urothelial carcinoma of the urinary bladder (MPUC) is a rare variant of urothelial carcinoma which has aggressive clinical characteristics. The objective is to investigate the molecular subtypes of MPUC and the impact to the clinical outcome and determine whether MPUC represents a variant of adenocarcinoma. Materials and Methods: We evaluated surrogate immunohistochemical markers of luminal, basal, and p53-like subtypes and correlated with prognosis and the expression of markers related to bladder adenocarcinoma and glandular differentiation in 56 cases of MPUC (10 cases of transurethral resection and 46 cases of radical cystectomy). Biomarker expression in co-existing conventional urothelial carcinoma was also analyzed. Cox regression analysis was performed to study the impact of molecular subtype on the clinical outcome. Results: Thirty-four cases (61%) met criteria for the luminal subtype. Twenty-two cases (39%) displayed a p53-like subtype. In contrast, 40/56 (71%) cases of coexisting conventional urothelial carcinoma were classified as luminal subtype and 16/56 (29%) cases were designated as p53-like subtype. There was no significant survival difference between luminal subtype and p53-like subtype. CDX2, villin, and cadherin 17 were negative in all cases. MUC1 was strongly and diffusely expressed in the stroma-facing surface of MPUC tumor cells in all the cases. Conclusions: Our findings suggest that MPUC possesses characteristics of luminal and p53-like subtypes, and does not harbor phenotypic features of the basal subtype. There is no significant difference in the prognosis between luminal and p53-like subtype MPUC. MPUC is not a variant of adenocarcinoma and does not represent a form of glandular differentiation, in contrast to other organ sites.

KW - Basal/luminal subtype

KW - Micropapillary variant

KW - Molecular classification

KW - Molecular genetics

KW - Urinary bladder

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U2 - 10.1016/j.urolonc.2019.10.013

DO - 10.1016/j.urolonc.2019.10.013

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SN - 1078-1439

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