Abstract
PurposeRadical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines.Material and MethodsImmunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting.ResultsMUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p≤0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9).ConclusionThe expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma.
Highlights
Bladder cancer (BCa) is the fifth common malignancy in the United States accounting for nearly 72,570 new cases and 15,210 cancer-related deaths during 2013 [1]
MUC1 staining increased from normal urothelium (n = 27, 0.3560.12) to urothelial carcinoma (UC, n = 323, H-score, 2.460.22, p#0.0001)
We explored the expression profile of transmembrane mucins (MUC1 and MUC4) in urothelial carcinoma tissue sections and three tissue tissue microarrays (TMAs)
Summary
Bladder cancer (BCa) is the fifth common malignancy in the United States accounting for nearly 72,570 new cases and 15,210 cancer-related deaths during 2013 [1]. The urothelial carcinoma (UC) is the most common histologic type of BCa that accounts for .90% of the newly diagnosed cases. UCs at the time of diagnosis range from superficial low-grade papillary lesions (associated with better prognosis) to highly invasive malignant carcinomas (highly aggressive with a low survival). 70–80% of newly diagnosed UCs are ‘‘non–muscle invasive’’ wherein the disease is confined to the bladder mucosa or lamina propria (stage Ta/T1 according to TNM classification) [2]. The cases of high grade invasive carcinoma are associated with high probability of metastasis and mortality [3,4]. Cytology is highly specific for high-grade urothelial carcinoma but not for low-grade urothelial carcinoma
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