An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms.

OBJECTIVE: Our purpose was to evaluate the use of transvaginal ultrasonography for the detection of endometrial disease in a population of postmenopausal women who were without symptoms. STUDY DESIGN: Postmenopausal women were screened for potential inclusion in 2 multicenter, double-blind, placebo-controlled studies of 2 years' duration to evaluate the safety and efficacy of idoxifene in the prevention of osteoporosis. Baseline endometrial evaluation was performed by transvaginal ultrasonography and aspiration biopsy of the endometrium. RESULTS: A total of 1926 women were screened by transvaginal ultrasonography, and 1833 of them had endometrial thickness < or =6 mm. Five cases of endometrial abnormality (adenocarcinoma [n = 1] and atypical hyperplasia [n = 4]) were detected in the 1750 women from this cohort who underwent biopsy. The negative predictive value was >99%. One case of adenocarcinoma was detected in the 42 women who had endometrial thickness >6 mm and underwent biopsy. However, the sampling rate (45%) of women with endometrial thickness >6 mm was too low for confidence in the positive predictive value of 2%. CONCLUSIONS: Despite a high negative predictive value, transvaginal ultrasonography may not be an effective screening procedure for detection of endometrial abnormality in untreated postmenopausal women who are without symptoms.

FrzB-2: a human secreted frizzled-related protein with a potential role in chondrocyte apoptosis.

OBJECTIVE: To characterize a novel secreted frizzled-related protein (SFRP) and determine its tissue distribution at the mRNA and protein level. METHODS: The FrzB-2 gene was identified by expressed sequence tag (EST) analysis of human tissue-derived libraries. Tissue distribution of FrzB-2 mRNA was determined by Northern blot analysis and in situ hybridization. FrzB-2 protein reactivity was localized in human OA articular cartilage by immunocytochemistry, using a polyclonal antibody against a peptide sequence unique to FrzB-2. Apoptosis was detected in articular cartilage sections using Tunel staining. RESULTS: ESTs corresponding to FrzB-2 were found in osteoblast, chondrosarcoma, osteosarcoma, osteoclastoma and synovial fibroblast libraries. FrzB-2 mRNA is expressed in a number of tissues and cell types including bone-related cells and tissues such as primary human osteoblasts and osteoclastoma. In situ hybridization studies showed strong FrzB-2 mRNA expression in human chondrocytes in human osteoarthritic (OA) cartilage but negligible levels in normal cartilage chondrocytes. The FrzB-2 cDNA encodes a secreted 40 kDa protein consisting of 346 amino acids. FrzB-2 is 92. 5% identical to the rat orthologue, DDC-4, which has been shown to be associated with physiological apoptosis. FrzB-2 protein was selectively detected in human OA articular cartilage by immunocytochemistry, using a polyclonal antibody. Consistent with its potential role in apoptosis, positive FrzB-2 staining and Tunel positive nuclei staining were detected in chondrocyte clones in sections of human OA cartilage. CONCLUSION: These data suggest that FrzB-2 may play a role in apoptosis and that the expression of this protein may be important in the pathogenesis of human OA.