Aberrant gene expression in epithelial cells of mixed odontogenic tumors.

Comparative investigations of odontogenic cells in normally forming teeth and tumors may provide insights into the mechanisms of the differentiation process. The present study is devoted to late phenotypic markers of ameloblast and odontoblast cells, i.e., proteins involved in biomineralization. The in situ expression of amelogenins, keratins, collagens type III and IV, vimentin, fibronectin, osteonectin, and osteocalcin was performed on normal and tumor odontogenic human cells. The pattern of protein expression showed some similarities between ameloblasts and odontoblasts present in normally developing human teeth and cells present in neoplastic tissues of ameloblastic fibroma, ameloblastic fibro-odontomas, and complex odontomas. Amelogenins (for ameloblasts) and osteocalcin (for odontoblasts) were detected in cells with well-organized enamel and dentin, respectively. In contrast, "mixed" cells located in epithelial zones of mixed odontogenic tumors co-expressed amelogenins and osteocalcin, as shown by immunostaining. The presence of osteocalcin transcripts was also demonstrated by in situ hybridization in these cells. Keratins and vimentin were detected in the same epithelial zones. Tumor epithelial cells were associated with various amounts of polymorphic matrix (amelogenin- and osteocalcin-immunoreactive), depending on the types of mixed tumors. No osteocalcin labeling was found in epithelial tumors. This study confirms that the differentiation of normal and tumor odontogenic cells is accompanied by the expression of some common molecules. Furthermore, the gene products present in normal mesenchymal cells were also shown in odontogenic tumor epithelium. These data may be related to a tumor-specific overexpression of the corresponding genes transcribed at an undetectable level during normal development and/or to an epithelial-mesenchymal transition proposed to occur during normal root formation. A plausible explanation for the results is that the odontogenic tumor epithelial cells are recapitulating genetic programs expressed during normal odontogenesis, but the tumor cells demonstrate abnormal expression patterns for these genes.

Molecular cloning of novel leucine-rich repeat proteins and their expression in the developing mouse nervous system.

It is well established that leucine-rich repeat (LRR) proteins such as connectin, slit, chaoptin, and Toll have pivotal roles in neuronal development in Drosophila as cell adhesion molecules. However, to date, little information concerning mammalian LRR proteins has been reported. In the present study, we sought LRR proteins of the mouse brain, based on the assumption that fundamental mechanisms are conserved between different species. We screened a neonatal mouse brain cDNA library with a human partial cDNA encoding LRR protein as a probe. We obtained two independent cDNAs encoding LRR proteins, designated NLRR-1 and NLRR-2 (Neuronal Leucine-Rich Repeat proteins). We analyzed the whole sequence of NLRR-1 and partial sequence of NLRR-2. Sequence analysis showed that these two clones are about 60% homologous to each other, and that NLRR-1 protein is a transmembrane protein. Northern blot analysis and in situ hybridization histochemistry showed that both NLRR-1 and NLRR-2 mRNAs were expressed primarily in the central nervous system (CNS); NLRR-1 mRNA was also detected in the non-neuronal tissues such as cartilage, while NLRR-2 mRNA expression was confined to the CNS at all developmental stages. These results suggest that there is at least one LRR protein family in the mouse and that these molecules may play significant but distinct roles in neural development and in the adult nervous system.

Non-Hodgkin's lymphoma of the pleural cavity developing from long-standing pyothorax. Summary of clinical and pathological findings in thirty-seven cases.

Our previous study suggested a close relation between a preceding chronic tuberculous pyothorax and the development of non-Hodgkin's lymphoma (NHL) in the pleural cavity. To confirm this further, 37 cases were collected from Japanese hospitals, and their clinical and pathological findings summarized. The age at first admission for lymphoma of patients ranged from 46 to 81 (mean 63) years, the male to female ratio being 5.2:1. All patients were admitted after a 22-55 (mean 33) year history of pyothorax resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis (29 cases) or tuberculous pleuritis (seven cases). The most common presenting symptom was chest pain. The main tumor mass, detected by chest roentgenogram and computed tomographic scans, was situated in the pleura (28 patients), the lung near the pleura (five patients) and the pleura and lung (four patients). The diagnosis of pleural NHL was made by biopsy for 31 of the patients and at autopsy for the other six. Histologically 30 (81%) of the 37 cases were of the diffuse large cell type, and of these the immunoblastic type was the most common (22 cases). Immunological and immunohistologic studies revealed a B-cell nature of the proliferating cells in all but one tumor. Thirty-two patients received chemotherapy and/or radiotherapy. Twenty-seven patients died between one and 144 (median eight) months of diagnosis. Autopsies carried out in 23 cases revealed the disease to have been localized to the thorax in 11 patients. These findings indicated that malignant B-cell lymphoma arose as a monoclonal growth from a pool of proliferating polyclonal B lymphocytes in tissues affected by the chronic tuberculous pyothorax.