Clinicopathologic features and utility of immunohistochemical markers in signet-ring cell adenocarcinoma of the bladder

Anil A. Thomas, Andrew J. Stephenson, Steven C. Campbell, J. Stephen Jones, Donna E. Hansel

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Signet-ring adenocarcinoma is an aggressive form of primary bladder adenocarcinoma that has been associated with poor outcomes. The utility of immunohistochemical markers in tumors with signet-ring morphology may vary from more typical adenocarcinomas arising at the same location, although this has not been examined in bladder adenocarcinoma. We examined a series of bladder adenocarcinomas to determine the impact of signet-ring cell features on clinical outcomes and immunohistochemical findings. We identified 25 patients with bladder adenocarcinoma, ranging in age from 28 to 78 years (mean, 57 years) and with a male-female ratio of 18:7. Six cases were urachal in origin. Signet-ring cells occurred in 19 of 25 bladder adenocarcinomas (76%) and ranged from 5% to 100% of tumor volume, with most tumors demonstrating more than 60% signet-ring cell differentiation (15/19), when present. Regional lymph node metastases were present in 8 of 19 patients (42%) who underwent cystectomy. The percentage of tumor containing signet-ring cells was significantly associated with the presence of adverse pathologic features (defined as unresectable primary tumor or regional lymph node metastasis, P = .013) and decreased overall survival (P = .034), and the latter remained significant in multivariable analysis after adjusting for positive soft tissue margins (P = .026). A comparison between immunohistochemical markers frequently used to analyze bladder adenocarcinoma demonstrated decreased expression of several markers in signet-ring (n = 9) versus colonic-type (n = 8) morphology, including CDX-2, β-catenin, and E-cadherin, although these results did not reach statistical significance. In summary, the extent of signet-ring differentiation in bladder adenocarcinoma is associated with worsened survival and higher stage disease; the utility of immunohistochemical analysis in foci consisting of predominant signet-ring cells may be limited, although further studies that address this finding are needed.

Original languageEnglish (US)
Pages (from-to)108-116
Number of pages9
JournalHuman Pathology
Issue number1
StatePublished - Jan 2009
Externally publishedYes


  • Adenocarcinoma
  • Bladder neoplasms
  • Clinicopathologic
  • Cystectomy
  • Immunohistochemistry
  • Signet-ring cell carcinoma
  • Treatment outcome
  • Urachus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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