Occult recurrence of monomorphic epitheliotropic intestinal T‐cell lymphoma and the role of MATK gene expression in diagnosis

Monomorphic epitheliotropic intestinal T‐cell lymphomas (MEITL), formerly Type II enteropathy‐associated T‐cell lymphomas (EATL), are rare peripheral T‐cell lymphomas. They are associated with poor survival outcomes, in part because of their late diagnosis. Although MEITLs may be reliably diagnosed based on histological and immunophenotypic findings, overlaps with other NK/T and T‐cell lymphomas may confound the diagnosis. The distinctive high‐level nuclear staining of the novel marker Megakaryocyte‐associated tyrosine kinase (MATK) in MEITLs is an invaluable tool in distinguishing MEITL from classical EATL and other NK/T or T‐cell lymphomas. 18‐Fluorine‐2‐fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG PET) has been shown to be a useful tool in the staging and follow‐up of aggressive lymphomas. Herein, we describe an unusual case of occult hepatic recurrence of MEITL that was non‐avid on ¹⁸F‐FDG PET, in which diagnosis was confirmed based on the expression of MATK in tumour cells. Copyright © 2016 John Wiley & Sons, Ltd.     

Trastuzumab-induced recruitment of Csk-homologous kinase (CHK) to ErbB2 receptor is associated with ErbB2-Y1248 phosphorylation and ErbB2 degradation to mediate cell growth inhibition

The inhibitory effect of trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of ErbB2, is associated with its ability to induce ErbB2-Y1248 phosphorylation, and the status of phosphorylated ErbB2-Y1248 (ErbB2-pY1248) may correlate with the sensitivity of breast cancers to trastuzumab. The mechanisms of which remain unclear. Here, we show that binding of trastuzumab to ErbB2 activates ErbB2 kinase activity and enhances ErbB2-Y1248 phosphorylation in trastuzumab-sensitive breast cancer cells. This in turn increases the interaction between ErbB2 and non-receptor Csk-homologous kinase (CHK), leading to growth inhibition of breast cancer cells. Overexpression of CHK mimics trastuzumab treatment to mediate ErbB2-Y1248 phosphorylation, Akt downregulation, and growth inhibition of trastuzumab-sensitive breast cancer cells. CHK overexpression combined with trastuzumab exerts an additive effect on cell growth inhibition. We further demonstrate that positive ErbB2-pY1248 staining in ErbB2-positive breast cancer biopsies correlates with the increased trastuzumab response in trastuzumab neoadjuvant settings. Collectively, this study highlights an important role for ErbB2-pY1248 in mediating trastuzumab-induced growth inhibition and trastuzumab-induced interactions between CHK and ErbB2-pY1248 is identified as a novel mechanism of action that mediates the growth inhibition of breast cancer cells. The novel mechanistic insights into trastuzumab action revealed by this study may impact the design of next generation of therapeutic monoclonal antibodies targeting receptor tyrosine kinases, as well as open new avenues to identify novel targets for the treatment of ErbB2-positive cancers.     

Primary cutaneous peripheral T-cell lymphoma with a late relapse solely in the ileum mimicking monomorphic epitheliotropic intestinal T-cell lymphoma

Background

Primary cutaneous peripheral T-cell lymphomas (PC-PTCLs) are classified into mycosis fungoides (MF) and other rare specific types; and those do not fit into any specific entities are designated as PTCL, not otherwise specified (NOS), an aggressive neoplasm. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is an aggressive primary intestinal T-cell lymphoma with enteropathy in the non-neoplastic mucosa. We report a rare case of PC-PTCL-NOS with a late relapse solely in the ileum after complete remission. We discuss the importance of evaluating enteropathy, megakaryocyte-associated tyrosine kinase (MATK) immunostaining, and the implication of clonal relationship of metachronous lymphomas.

Gene expression in giant-cell tumors

Malignant transformation is thought to be associated with changes in the expression of a number of genes, and this alteration in gene expression is considered critical to the development of the malignant phenotype. In this study, gene expression in 8 samples of giant-cell tumor (GCT) of bone, as well as in bone at the site of osteoarthritis and in a variety of normal tissues, was determined at Gene Logic Inc (Gaithersburg, Md) with the use of Affymetrix GeneChip U_133 arrays containing approximately 40,000 genes/expressed sequence tags (ESTs). Gene-expression analysis was performed with the use of the Gene Logic GeneExpress Software System. Differences in gene expression between GCTs and bone were observed. In addition, genes expressed uniquely in GCTs among these and 519 samples from 20 other tissue types were identified. Some of the genes that were found to be overexpressed in GCTs, such as tartrate-resistant acid phosphatase and the lysosomal H + -transporting ATPase, are also expressed by osteoclasts. Osteoprotegrin ligand (OPGL) was also selectively overexpressed in GCTs. The genes found to be overexpressed in GCTs appear to reflect the genetic profile of osteoclast-lineage cells and also the genetic profile of an osteoclastogenic environment. The genes identified in this study may play a role in the pathogenesis of GCTs, confirm the likely importance of OPGL in GCT pathogenesis, and may indicate other possible targets to which antitumor therapy could be directed.