KLHL6 Is Preferentially Expressed in Germinal Center-Derived B-Cell Lymphomas.

OBJECTIVES: KLHL6 is a recently described BTB-Kelch protein with selective expression in lymphoid tissues and is most strongly expressed in germinal center B cells. METHODS: Using gene expression profiling as well as immunohistochemistry with an anti-KLHL6 monoclonal antibody, we have characterized the expression of this molecule in normal and neoplastic tissues. Protein expression was evaluated in 1,058 hematopoietic neoplasms. RESULTS: Consistent with its discovery as a germinal center marker, KLHL6 was positive mainly in B-cell neoplasms of germinal center derivation, including 95% of follicular lymphomas (106/112). B-cell lymphomas of non-germinal center derivation were generally negative (0/33 chronic lymphocytic leukemias/small lymphocytic lymphomas, 3/49 marginal zone lymphomas, and 2/66 mantle cell lymphomas). CONCLUSIONS: In addition to other germinal center markers, including BCL6, CD10, HGAL, and LMO2, KLHL6 immunohistochemistry may prove a useful adjunct in the diagnosis and future classification of B-cell lymphomas.

Changes of gene expression in gastric preneoplasia following Helicobacter pylori eradication therapy.

Helicobacter pylori causes gastric preneoplasia and neoplasia. Eradicating H. pylori can result in partial regression of preneoplastic lesions; however, the molecular underpinning of this change is unknown. To identify molecular changes in the gastric mucosa following H. pylori eradication, we used cDNA microarrays (with each array containing approximately 30,300 genes) to analyze 54 gastric biopsies from a randomized, placebo-controlled trial of H. pylori therapy. The 54 biopsies were obtained from 27 subjects (13 from the treatment and 14 from the placebo group) with chronic gastritis, atrophy, and/or intestinal metaplasia. Each subject contributed one biopsy before and another biopsy 1 year after the intervention. Significant analysis of microarrays (SAM) was used to compare the gene expression profiles of pre-intervention and post-intervention biopsies. In the treatment group, SAM identified 30 genes whose expression changed significantly from baseline to 1 year after treatment (0 up-regulated and 30 down-regulated). In the placebo group, the expression of 55 genes differed significantly over the 1-year period (32 up-regulated and 23 down-regulated). Five genes involved in cell-cell adhesion and lining (TACSTD1 and MUC13), cell cycle differentiation (S100A10), and lipid metabolism and transport (FABP1 and MTP) were down-regulated over time in the treatment group but up-regulated in the placebo group. Immunohistochemistry for one of these differentially expressed genes (FABP1) confirmed the changes in gene expression observed by microarray. In conclusion, H. pylori eradication may stop or reverse ongoing molecular processes in the stomach. Further studies are needed to evaluate the use of these genes as markers for gastric cancer risk.