Frequent Loss of KAI1 Expression in Squamous and Lymphoid Neoplasms : An Immunohistochemical Study of Archival Tissues

The metastasis suppressor gene KAI1 was identified by its ability to inhibit the formation of pulmonary metastases in experimental models for prostatic carcinoma. Down-regulation of this gene may be correlated with the invasive phenotype in melanomas and colon and bladder carcinomas and with the metastatic phenotype in carcinomas of the lung, breast, prostate, and pancreas. The goal of our study was to establish an immunohistochemical method to detect KAI1 expression in archival tissues. Using cell lines with known KAI1 levels and paraffin-embedded KAI1 positive tissues as controls, we observed strong membrane staining in lymphoid follicular centers and squamous epithelia. We then demonstrated the utility of our assay by studying KAI1 expression in 34 lymphoid and 57 squamous lesions. All eight reactive lymph nodes were KAI1 positive. In contrast, three of 13 follicular small cleaved and five of 13 diffuse large cell lymphomas were KAI1 negative. Seventy-nine percent (37 of 47) of invasive squamous cell carcinomas from the lung (n = 15), head and neck (n = 18), and cervix (n = 14) showed extensive KAI1 down-regulation. Loss of KAI1 expression was also found in a subset of 10 high-grade cervical dysplasias. Our data show that (i) immunohistochemistry is a suitable technique for evaluating KAI1 expression in archival tissues; (ii) KAI1 was not expressed in a subset of both low-grade and high-grade lymphomas; and (iii) there was extensive down-regulation of KAI1 in squamous cell carcinomas, suggestive of an important role of the gene in the suppression of invasion in these malignancies.     

An Investigation of Immunological Tolerance Based on Chimaera Analysis

Newborn mice of strain A were injected intravenously at birth with 9–15 million spleen cells from adult CBA donors. The recipients exhibited splenomegaly and other signs of graft-versus-host reaction during the first 3 weeks of life. Adult survivors were uniformly tolerant of CBA skin. They showed no sign of a continuing graft-versus-host reaction. The spleens of the treated mice were tested for the presence of immunologically competent donor and host cells by Simonsen's discriminant spleen assay. From the age of 7 days onwards the spleens were found to contain a small percentage of donor cells which were immunologically active against antigens of a third strain. In spleens from adult survivors activity, attributable to the host component, against third-party antigens was undiminished as compared with that of untreated A-strain mice. But activity against the CBA donor strain was absent.     

Lymphoid adenohypophysitis

A rare case of lymphoid adenohypophysitis in a 28-year-old woman with temporal relation to pregnancy is described. A CT scan disclosed a round, contrast-enhancing sellar mass simulating pituitary adenoma, and endocrine evaluation showed mild hypopituitarism. Histological examination of the specimen obtained by transsphenoidal hypophysectomy after uneventful natural labour showed marked diffuse infiltration of mature lymphocytes with many germinal centers within lymphoid follicles. This finding was the same as previously reported. The present case makes a total of 15 cases reported in the world literature up to date. To our knowledge, no report has been documented in Japan.     

Lymphoid neoorganogenesis

Lymphoid organ development and inflammation have previously been considered as distinct mechanistically and functionally. In recent years, it has been realized that these phenomena have much in common. This insight has been gained from the recognition that cytokines of the lymphotoxin (LT)/tumor necrosis factor (TNF) family are involved in both processes. The members of the family, LT-α, LT-Β, and TNF-α, and their multiple receptors participate combinatorially in lymphoid organ development and chronic inflammation. When inflammation that arises in microbial infection or autoimmune disease becomes chronic, it can take on the appearance of organized lymphoid tissue and has been called a tertiary lymphoid organ. Data with transgenic and knockout mice suggest that the process is cytokine-mediated and could be called “lymphoid neo-organogenesis.” LT as LT-α₃ and LT-α₁Β₂ plays a key role in these processes. Data obtained in vitro in an endothelial cell line and in vivo in transgenic and knockout mice indicate that LT influences these events through induction of adhesion molecules such as E-selectin adhesion molecule (ELAM), vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), mucosal addressin cellular adhesion molecule (MAdCAM), and peripheral node addressin (PNAd), and chemokines.     

Lymphoid precursors

Lymphopoiesis of mature and diverse populations of T, B and NK (natural killer) cells from multipotent hematopoietic stem cells is an ideal model of tissue generation and regeneration. Identification and isolation of hematolymphoid stem and progenitor cells in several laboratories over the past several years have provided populations that can be studied biologically for lineage commitment and biochemically for receptor function, signal transduction and selective gene expression. These studies may ultimately provide candidate genes involved in lineage commitment, cell death or survival, self-renewal and migratory capacities of progenitors.     

Organization of the Invading Lymphoid Tissue in Human Lymphoid Thyroiditis

The structural pattern of lymphoid tissue in lymphoid thyroiditis was analyzed by thin-section histology in ten thyroidectomy specimens representing focal and massive thyroiditis. Special attention was devoted to the identification of high-endo-thelium postcapillary venules, which were found in eight cases, they were absent only in two of the 'focal' cases. These specific vessels were always found immediately outside secondary nodules ('cortex'), in a narrow zone obviously analogous to the paracortical zone of lymph nodes Thyroiditic tissue thus presented a three-zonal stratification similar to that seen in lymph nodes, with the medullary zone represented by the lymphoid invasion zone within still preserved thyroid parenchyma. It appeared still more akin, however, to the subepithelial zone of gut-associated lymphoid tissue. A striking finding in all cases was the predominance of mature plasma cells among the lymphoid cells invading still preserved thyroid follicles     

Electrophoresis of Lymphoid Cells

The electrophoretic mobility of small lymphoid cells in the thymus, lymph nodes, and spleen was measured. The distribution patterns were organ specific. The majority of the thymic cells were slow with a small 'tail' of faster cells. Both lymph node and spleen cells showed a fast and a slow cell population with a difference in mean electrophoretic mobility of about 40%. The percentage of cells to the fast and slow groups was similar to the percentage of T- and B-cells in these organs It is therefore suggested that T-and B-cells may be characterized by their different electrophoretic mobilities and also that there may be a change in the net surface charge during maturation from thymocyte to T-lymphocyte.