High molecular weight cytokeratin antibody (clone 34βE12):: a sensitive marker for differentiation of high-grade invasive urothelial carcinoma from prostate cancer

Aims: There is no well-established positive immunomarker for urothelial carcinoma. We evaluated the diagnostic utility of high molecular weight cytokeratin (HMWCK) antibody clone 34betaE12 in differentiating high-grade invasive urothelial carcinoma from prostate cancer. Methods and results: Formalin-fixed paraffin-embedded sections from 28 cases of high-grade invasive urothelial carcinoma (20 not otherwise specified (UC-NOS), eight with glandular differentiation) and 20 cases of poorly differentiated prostate carcinoma were immunostained with a monoclonal antibody to carcinoembryonic antigen (CEA), clone 85A12 and with HMWCK antibody clone 34betaE12 after microwave pretreatment or protease 24 predigestion. All cases of UC-NOS expressed HMWCK on 34betaE12 immunostaining after microwaving or enzyme predigestion. Immunoreactivity was intense and diffuse in all the cases after microwave pretreatment, whilst with enzyme predigestion immunoreactivity was sometimes patchy with <50% tumour cells positive in 20% of cases. In comparison with 34betaE12, 85A12 was insensitive with 15% of UC-NOS cases totally CEA-negative and <50% tumour cell immunoreactivity in 60% of cases. Rare positive cells were present in two (10%) cases of prostate cancer with monoclonal anti-CEA and 34betaE12 on microwaved sections, but all the cases were HMWCK-negative using 34betaE12 on sections pretreated by enzyme digestion. Conclusions: HMWCK antibody clone 34betaE12, particularly when used with microwave heat retrieval, is a very sensitive positive marker for high-grade invasive urothelial carcinoma.