Correlation of cyclin D1 and E1 expression with bladder cancer presence, invasion, progression, and metastasis

Shahrokh F. Shariat, Raheela Ashfaq, Arthur I Sagalowsky, Yair Lotan

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

The objective of this study was to determine the correlation of the expression of cyclin D1 and E1 with the expression of commonly altered cell cycle regulators and bladder cancer presence, staging, and clinical outcomes. We performed immunohistochemical staining for cyclin D1, cyclin E1, p53, p21, p27, and retinoblastoma protein (pRB) on serial cuts from normal urothelium from 9 controls, radical cystectomy specimens from 226 consecutive patients with advanced transitional cell carcinoma, and lymph nodes with metastasis from 50 of the 226 cystectomy patients. Cyclin D1 and E1 immunoreactivity were considered low when samples demonstrated less than 10% and 30% nuclear reactivity, respectively. Normal bladder urothelium from all 9 control patients showed uniformly intense expression of cyclin D1 and E1. Cyclin D1 expression was low in 99 (43.8%) of 226 cystectomy specimens and 25 (50.0%) of 50 metastatic lymph node specimens. Cyclin D1 immunoreactivity was not associated with any pathologic characteristics or clinical outcomes. Cyclin E1 expression was low in 125 (55.3%) of 226 cystectomy specimens and 22 (44.0%) of 50 metastatic lymph node specimens. Low cyclin E1 expression was significantly associated with advanced pathologic stage, lymphovascular invasion, and lymph node metastases. In multivariate analyses, low cyclin E1 expression was significantly associated with bladder cancer-specific mortality (P = .048), but not disease recurrence (P = .056). Low cyclin E1 expression was significantly associated with altered expression of pRB, p27, and cyclin D1. Low cyclin D1 expression was significantly associated with altered expression of pRB, p21, and cyclin E1. Cyclin E1 expression stratifies patients with bladder transitional cell carcinoma into those with more "indolent" behavior and those with features of biologically and clinically aggressive disease.

Original languageEnglish (US)
Pages (from-to)1568-1576
Number of pages9
JournalHuman Pathology
Volume37
Issue number12
DOIs
StatePublished - Dec 2006

Fingerprint

Cyclin D1
Cyclins
Urinary Bladder Neoplasms
Neoplasm Metastasis
Cystectomy
Retinoblastoma Protein
Lymph Nodes
Urothelium
Transitional Cell Carcinoma
Urinary Bladder
Neoplasm Staging
Cell Cycle
Multivariate Analysis
Staining and Labeling
Recurrence
Mortality

Keywords

  • Cyclin D1
  • Cyclin E1
  • p21
  • p27
  • p53
  • Retinoblastoma
  • Transitional cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Correlation of cyclin D1 and E1 expression with bladder cancer presence, invasion, progression, and metastasis. / Shariat, Shahrokh F.; Ashfaq, Raheela; Sagalowsky, Arthur I; Lotan, Yair.

In: Human Pathology, Vol. 37, No. 12, 12.2006, p. 1568-1576.

Research output: Contribution to journalArticle

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