Protein expression of matriptase and its cognate inhibitor HAI-1 in human prostate cancer: a tissue microarray and automated quantitative analysis.

Recent studies have suggested that matriptase, a transmembrane serine protease and its cognate inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1) are important in the progression of many cancers. Limited quantitative data are available on these proteins in prostate cancer. To validate the roles of matriptase and HAI-1 in prostate cancer and its progression, a prostate cancer tissue microarray was constructed. The tissue microarray includes 41 localized prostate cancers (Pca_local), 18 aggressive prostate cancers, 18 metastatic prostate cancers, 24 benign prostate hyperplasias, 18 high-grade intraepithelial neoplasias (HGPIN), and 41 benign prostate tissues. The cellular expression levels of matriptase and HAI-1 were quantified using automated quantitative analysis. We found that matriptase expression levels were significantly higher in Pca_local (P<0.0001) and HGPIN (P<0.05) compared with benign prostate tissue. Matriptase levels were significantly decreased in metastatic cancer when compared with all other tissue types (P<0.05). Compared with benign prostate tissue, HAI-1 expression levels were significantly higher in all proliferative prostate diseases (benign prostate hyperplasia, HGPIN, localized and aggressive cancers, and metastases) (P<0.001); yet, no significant differences were found in HAI-1 expression levels among the diseased tissue types. These results suggest that an increase of matriptase may be useful as a marker for detection of Pca_local, whereas a decrease of matriptase expression may signal prostate cancer progression. HAI-1 seems to be a marker of prostate epithelial cell proliferation.

Fraser syndrome: affected siblings born to nonconsanguineous parents and diagnosed at autopsy.

Fraser syndrome (MIM 219000) is a rare genetic disorder with major features including cryptophthalmos, syndactyly, and genital anomalies. We report 2 independently autopsied children of the same nonconsanguineous parents. The siblings exhibit similar clinical features, all of which are consistent with a diagnosis of Fraser syndrome. The gross and microscopic findings provide insight into the highly variable clinical presentation of Fraser syndrome. Molecular diagnostic studies of the index case failed to identify one of the known gene mutations in the FRAS1 and FREM2 genes associated with Fraser syndrome. This raises the possibility that other genes or undetected mutations in the FRAS1/FREM2 genes may cause Fraser syndrome.