Leukocyte-specific phosphoprotein-1 and PU.1: two useful markers for distinguishing T-cell-rich B-cell lymphoma from lymphocyte-predominant Hodgkin's disease.

BACKGROUND AND OBJECTIVES: T-cell-rich B-cell lymphoma is a rare variant of diffuse large B-cell lymphoma. It shows morphologic, phenotypic and molecular similarities to lymphocyte predominant Hodgkin's disease, and in consequence the two diseases may sometimes be difficult to distinguish. In this paper, we have evaluated the usefulness of the pan-leukocyte marker LSP1 and the transcription factor PU.1 for resolving such diagnostic problems. DESIGN AND METHODS: Immunohistochemical techniques were used to investigate the expression of LSP1 and PU.1 in 34 tumors, comprising typical examples of T-cell-rich B-cell lymphoma (15 cases), lymphocyte-predominant Hodgkin's disease (13 cases), and lymphocyte-rich classical Hodgkin's disease (6 cases). RESULTS: The neoplastic cells of T-cell-rich B-cell lymphoma were LSP1-positive and PU.1-negative, whereas the lymphocytic and/or histiocytic (L&H) cells of lymphocyte-predominant Hodgkin's disease were mostly LSP1-negative, with variable PU.1 expression. The two markers did not discriminate between T-cell-rich B-cell lymphoma and lymphocyte-rich classical Hodgkin's disease, whilst they concurred to the distinction between lymphocyte-predominant and lymphocyte-rich classical Hodgkin's disease by integrating the already available tools. INTERPRETATION AND CONCLUSIONS: Antibodies to LSP1 and PU.1 may represent useful reagents for the differential diagnosis between T-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin's disease.

Detection of the human organic anion transporters SLC21A6 (OATP2) and SLC21A8 (OATP8) in liver and hepatocellular carcinoma.

Transport proteins mediating the selective uptake of organic anions into human hepatocytes include the organic anion transporters SLC21A6 (also termed OATP2, OATP-C, or LST-1) and SLC21A8 (OATP8). Both transporters are localized to the basolateral membrane of human hepatocytes. Because of the importance of these transporters for hepatobiliary elimination, including the removal of bilirubin and its conjugates from the blood circulation, we have generated monoclonal antibodies for studies on the expression and localization of these transport proteins. We describe two antibodies, designated monoclonal antibody MDQ (mMDQ) and monoclonal antibody ESL (mESL), directed against the amino terminus and the carboxyl terminus of human SLC21A6, respectively. Both antibodies have been characterized by immunoblot analysis, immunoprecipitation, and immunofluorescence microscopy. While mESL reacted specifically with SLC21A6, mMDQ detects both SLC21A6 and SLC21A8. Neither of the two antibodies reacted with other human, or with dog, rat, or mouse liver SLC21A family members. Antibody mMDQ may be used for the simultaneous detection of SLC21A6 and SLC21A8 in immunoblotting because of its immunoreactivity with both molecules and because of the different molecular masses of both glycosylated proteins in human hepatocytes. This is exemplified in hepatocellular carcinomas where SLC21A6 and SLC21A8 were differentially synthesized and showed an irregular staining pattern. Both transport proteins have not been detected in human hepatoma HepG2 cells. In routine paraffin sections, 10 of 12 hepatocellular carcinomas were focally positive with antibody mMDQ. In contrast, cholangiocarcinomas and liver metastases of colorectal and pancreatic adenocarcinoma were negative without exception. This suggests the usefulness of SLC21A6/SLC21A8 within a panel of tumor markers for hepatocellular carcinomas. Moreover, both antibodies should be useful in studies on the expression and localization of two important uptake transporters of human hepatocytes under physiologic and pathophysiologic conditions.