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

Hum Pathol. 2009 Jan;40(1):108-16. doi: 10.1016/j.humpath.2008.06.022. Epub 2008 Sep 11.

Abstract

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, beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Signet Ring Cell / genetics
  • Carcinoma, Signet Ring Cell / pathology*
  • Carcinoma, Signet Ring Cell / surgery
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Cystectomy
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / surgery

Substances

  • Biomarkers, Tumor