title: Clinicopathologic features and utility of immunohistochemical markers in signet-ring cell adenocarcinoma of the bladder.
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.
authors.affiliation: Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Thomas
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Stephenson
authors.forename: Steven C
authors.initials: SC
authors.lastname: Campbell
authors.forename: J Stephen
authors.initials: JS
authors.lastname: Jones
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hansel
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D015653:Cystectomy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor