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

OBJECTIVE: To 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 METHODS: Clinical 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. RESULTS: Increased 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, ß- 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 ß-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. CONCLUSIONS: Our 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.

EUS-FNA of the left adrenal gland is safe and useful

<p><b>INTRODUCTION</b>There are limited data on the use of endosonography-guided fine-needle aspiration (EUS-FNA) to determine the nature of left adrenal lesions. We described our experience in performing EUS-FNA of left adrenal lesions.</p><p><b>CLINICAL PICTURE</b>During a 20-week period, data on consecutive patients who underwent EUS with or without EUS-FNA were prospectively captured. Patients with a left adrenal mass and who underwent EUS-FNA formed our study population.</p><p><b>TREATMENT</b>EUS-FNA.</p><p><b>OUTCOME</b>A total of 119 consecutive patients underwent diagnostic EUS +/- FNA, during which the left adrenal gland was routinely examined. Twelve of these patients underwent EUS as part of lung cancer staging and among these 12 lung cancer patients, 2 had left adrenal masses detected by computed tomography (CT). EUS detected left adrenal nodules in 2 other patients which were not visualised by CT. The overall prevalence of a left adrenal mass was 3.4%; in the subgroup with confirmed lung cancer, the prevalence was 33.3%. All 4 patients were male, with a mean age of 76.3 years (range, 67 to 87). The mean size of the left adrenal lesion was 30.4 mm (range, 9 to 84.8). EUS-FNA of the left adrenal lesions was performed under Doppler guidance. The mean number of needle passes was 2 (range, 1 to 4). A cellular aspirate was obtained in all patients. No procedural complications occurred. Metastatic non-small cell lung cancer was diagnosed in 2 patients, including a lesion missed on CT. For the other 2 cases, EUS-FNA revealed benign adrenal cells.</p><p><b>CONCLUSIONS</b>EUS-FNA appears safe and useful for the evaluation of left adrenal masses.</p>