Detection of early squamous metaplasia in bladder biopsies of spinal cord injury patients by immunostaining for cytokeratin 14

Study design: A prospective, immunohistochemical study of bladder biopsies taken from spinal cord injury (SCI) patients. Objectives: To investigate whether cytokeratin 14 immunostaining may be useful to detect early squamous metaplasia in bladder biopsies from patients with SCI. Setting: Southport, United Kingdom. Methods: Biopsy of bladder mucosa was taken from adults with SCI, while they underwent an elective therapeutic procedure in the urinary tract. A total of, 54 biopsies, which showed transitional epithelium only with no evidence of squamous metaplasia on routine H&E staining, formed the study group. In all, 22 biopsies, which showed squamous metaplasia on routine H&E staining, acted as controls. All biopsies were benign with no evidence of dysplasia or malignancy. Immunohistochemical staining for cytokeratin 14 was performed on all biopsies in a single batch, using a standard avidin-biotin complex method. Results: All control biopsies showed positive immunostaining for cytokeratin 14 in basal and parabasal cells in areas of squamous metaplasia. Of the 54 biopsies, which showed only transitional epithelium on H&E staining, immunohistochemistry for cytokeratin 14 showed no staining in 47 biopsies. The remaining seven biopsies showed positive immunostaining for cytokeratin 14 in the epithelium, in individual cells or clusters of basal cells, revealing unexpected early squamous metaplasia in these biopsies. Conclusion: Immunostaining for cytokeratin 14 identifies an early phenotypic switch from transitional to squamous epithelium in bladder mucosa. Cytokeratin 14 staining is sufficiently sensitive to identify early squamous metaplasia, which is not yet evident on examination of routine H&E stained sections. This early identification may be of use in alerting physicians to change bladder management regimens to prevent predisposition to recurrent urinary infection and progression of squamous metaplasia. A cost/benefit analysis should be performed to assess the feasibility of routine cytokeratin 14 immunostaining of bladder biopsies from SCI patients.