Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties.

Alpha B-crystallin (CRYAB) maps within the nasopharyngeal carcinoma (NPC) tumor-suppressive critical region 11q22-23 and its downregulation is significantly associated with the progression of NPC. However, little is known about the functional impact of CRYAB on NPC progression. In this study we evaluated the NPC tumor-suppressive and progression-associated functions of CRYAB. Activation of CRYAB suppressed NPC tumor formation in nude mice. Overexpression of CRYAB affected NPC progression-associated phenotypes such as loss of cell adhesion, invasion, interaction with the tumor microenvironment, invasive protrusion formation in three dimensional Matrigel culture, as well as expression of epithelial-mesenchymal transition-associated markers. CRYAB mediates this ability to suppress cancer progression by inhibition of E-cadherin cytoplasmic internalization and maintenance of ß-catenin in the membrane that subsequently reduces the levels of expression of critical downstream targets such as cyclin-D1 and c-myc. Both ectopically expressed and recombinant CRYAB proteins were associated with endogenous E-cadherin and ß-catenin, and, thus, the cadherin/catenin adherens junction. The CRYAB α-crystallin core domain is responsible for the interaction of CRYAB with both E-cadherin and ß-catenin. Taken together, these results indicate that CRYAB functions to suppress NPC progression by associating with the cadherin/catenin adherens junction and modulating the ß-catenin function.

Oncogenic osteomalacia associated with an occult phosphaturic mesenchymal tumour: clinico-radiologico-pathological correlation and ultrastructural studies.

A middle-aged man presented with bone pain at multiple sites due to tumour-induced osteomalacia. The underlying occult phosphaturic mesenchymal tumour was identified by octreotide scan 5 years after presentation and confirmed by computed tomography. Tumour resection resulted in normalisation of blood chemistry and bone densitometry. Clinico-radiologico-pathological correlation and ultrastructural studies of the tumour threw light on the pathogenesis and pathophysiology of this rare disease.

Nasopharyngeal intraepithelial lesion: latent Epstein-Barr virus infection with malignant potential.

AIMS: To study the morphology and immunohistochemical expression of nasopharyngeal intraepithelial lesions and to understand their place in nasopharyngeal carcinogenesis. METHODS AND RESULTS: Nine cases of nasopharyngeal intraepithelial lesion (NPIL) were diagnosed during nasopharyngeal biopsy screening for nasopharyngeal carcinoma (NPC). Two cases were associated with early invasion. All cases demonstrated specific histological features and consistent positivity on in-situ hybridization for Epstein-Barr virus (EBV)-encoded RNA. Pure NPIL lesions showed low-grade morphology while lesions associated with early invasion were high grade. Immunohistochemical studies showed increased expression of bcl-2 and essentially negative findings for BZLF1 and LMP1. High-grade lesions had relatively stronger expression of bcl-2 and p53. CONCLUSIONS: NPIL harbours latent EBV infection and has malignant potential. Multiple steps are involved in its occurrence and progression. Low-grade and high-grade lesions should be managed differently.

Venous thromboembolism in the Chinese population--experience in a regional hospital in Hong Kong.

OBJECTIVE: To estimate the incidence and determine the characteristic features of venous thromboembolism in the Hong Kong Chinese population. DESIGN: Retrospective study. SETTING: Regional hospital, Hong Kong. SUBJECTS AND METHODS: Data were collected during a period of four years (1997-2000). Patients with duplex doppler ultrasonography or venography-documented venous thromboembolism and new episodes of deep vein thrombosis were identified from Department of Diagnostic Radiology records. Patients with high-probability ventilation-perfusion scans were identified from Department of Nuclear Medicine records and these scans were taken as evidence of pulmonary embolism. Patients with intermediate-probability ventilation-perfusion scans, with pulmonary embolism documented by either pulmonary angiography or spiral computed tomography scan, were also included in the study. Patients with autopsy-verified fatal pulmonary embolism were identified from Department of Pathology records. Patients with deep vein thrombosis at other sites were sought from patient discharge diagnostic coding data. Medical records were reviewed for patient characteristics and conditions associated with the development of venous thromboembolism. RESULTS: Three hundred and seventy-six Chinese patients had venous thromboembolism during the study period. Of these, 352 had peripheral deep vein thrombosis, five had deep vein thrombosis at other sites (cerebral sinus and portal vein thrombosis), 40 had pulmonary embolism (26 had concomitant deep vein thrombosis), and six had fatal pulmonary embolism shown at autopsy. CONCLUSION: The calculated annual incidence of venous thromboembolism in Hong Kong Chinese people was estimated at 16.6 events per 100,000 population, which is lower than incidence rates reported in Caucasians. The four conditions most commonly associated with venous thromboembolism were medical illness, malignancy, orthopaedic surgery, and intravenous drug use. Conditions associated with venous thromboembolism in patients younger than 45 years included intravenous drug use, thrombophilia, pregnancy, and the use of oral contraceptives.