Altered expression of cell adhesion molecules leads to differential uptake of hypericin in urothelial cancer

Abstract

ObjectiveTo elucidate the mechanism behind selective uptake of hypericin in bladder cancer after intravesical instillation for photodynamic diagnosis of urothelial cell carcinoma of bladder. Patients and methodsClinical studies were done on a series of 60 bladder cancer biopsies obtained from 28 patients who received intravesical instillations with 8 μM hypericin. Serial 5 μm cryosections were cut from 43 biopsies, and expression of the E-cadherin and associated catenins were determined using immunohistochemical and immunofluorescence staining. Hypericin was assessed using fluorescence confocal laser scanning microscopy. In addition, mRNA expression of these cell-adhesion molecules was analyzed in 17 biopsies using reverse transcription-PCR. ResultsIncreased variability in the expression of E-cadherin and associated molecules was found in high-grade, advanced stage bladder carcinoma. An inverse association was found between immunoreactivity for E-cadherin, β- and γ-catenin, and both stage and grade of cancer (P < 0.05). A positive association was observed between the hypericin fluorescence and tumor grade. There was a significant down-regulation of E-cadherin and β-catenin mRNA in grade 2 and 3 tumors. Although a small sample size was studied, it provided sufficient proof to support the hypothesis that altered expression of cell adhesion molecules would lead to preferential hypericin uptake in urothelial cell carcinoma. ConclusionsOur study has unraveled one of the many factors contributing to the selective uptake of hypericin in bladder cancer. We have thus identified the effects of alteration of E-cadherin–catenin complex and transformed intercellular junction in the modified paracellular uptake of hypericin that provides the rationale for using this photosensitizer in photodynamic diagnosis of bladder carcinoma.