1/8. Expression of Cdx1 and Cdx2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa--with special emphasis on participation in intestinal metaplasia of the human stomach.BACKGROUND: The caudal-type homeobox genes, Cdx1 and Cdx2, are candidates for directing intestinal development, differentiation, and maintenance of the intestinal phenotype. The aims of this study were: (1) to assess the normal tissue expression patterns of Cdx1 and Cdx2 in the human gastrointestinal tract and (2) to ascertain levels in intestinal metaplasia (IM) of the stomach associated with gastritis. methods: Fresh human tissues were collected by surgical resection from 39 patients after informed consent had been received. RNAs were extracted from 11 distinct sites in the gastrointestinal mucosa (gastric body, gastric antrum, duodenum, jejunum, ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum), and Northern hybridization was performed for Cdr1 and Cdx2 mRNAs. In addition, RNAs were also extracted from normal gastric mucosa, and gastric mucosa with mild to severe IM, confirmed histopathologically. Reverse-transcriptase polymerase chain reaction (RT-PCR) was then carried out for Cdx1 and Cdx2. RESULTS: The expression of Cdx1 mRNA increased gradually from the duodenum to the distal colon, with no expression detected in the stomach. Compared with the distribution of Cdx1 mRNA in the mouse gastrointestinal tract, the expression of Cdr1 mRNA in the human gastrointestinal tract showed greater predominance in the jejunum and ileum. The expression of Cdx2 mRNA increased gradually from the duodenum to the proximal colon and decreased from the ascending colon to the rectum. Compared with the expression pattern of Cdx2 mRNA in the mouse gastrointestinal tract, the expression of Cdx2 mRNA in the human gastrointestinal tract showed greater predominance in the ileum. By RT-PCR, both Cdx1 and Cdx2 mRNAs were detected in the mild and severe types of IM. However, neither of these mRNAs was identified in normal gastric mucosa without IM. CONCLUSIONS: Cdr1 and Cdx2 mRNAs are widely present in the human intestinal and colonic mucosae, but not in the gastric mucosa, suggesting that their expression may contribute to the intestinal phenotype. The high levels of these mRNAs in IM mucosa associated with chronic atrophic gastritis point to an association with this phenotypic shift in the gastric mucosa.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/8. Gastrointestinal stromal tumor in an XYY/XY male.A 32-year-old patient was diagnosed with a gastrointestinal stromal tumor of the small bowel. The pathologic diagnosis was confirmed by positive immunochemistry against CD34, and against CD117, the tyrosine-kinase c-kit. We performed a karyotypic analysis on the basis of the patient's tall stature and speech difficulties. One hundred thirty-two metaphases were obtained on PHA-stimulated peripheral blood; 123 of them presented an extra chromosome Y. fluorescence in situ hybridization using a Y satellite III probe showed the presence of a sole copy of chromosome Y in the tumor cells precluding a direct relationship between the extra chromosome Y and the initiation of the tumor. This is, to our knowledge, the second occurrence of a nonhematologic malignancy reported in this genetic disorder. A review of the malignancies observed in men with the XYY constitution is presented.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/8. Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma.Genetic alterations in enteropathy-type T-cell lymphoma (ETL) are unknown so far. In this series, 38 cases of ETL were analyzed by comparative genomic hybridization (CGH). CGH revealed chromosomal imbalances in 87% of cases analyzed, with recurrent gains of genetic material involving chromosomes 9q (in 58% of cases), 7q (24%), 5q (18%), and 1q (16%). Recurrent losses of genetic material occurred on chromosomes 8p and 13q (24% each), and 9p (18%). In this first systematic genetic study on ETL, chromosomal gains on 9q (minimal overlapping region 9q33-q34) were found to be highly characteristic of ETL. fluorescence in situ hybridization analysis on four cases of ETL, using a probe for 9q34, indicated frequent and multiple gains of chromosomal material at 9q34 (up to nine signals per case). Among 16 patients with ETL who survived initial disease presentation, patients with more than three chromosomal gains or losses (n = 11) followed a worse clinical course than those with three or less imbalances (n = 5). The observation of similar genetic alterations in ETL and in primary gastric (n = 4) and colonic (n = 1) T-cell lymphoma, not otherwise specified, is suggestive of a genetic relationship of gastrointestinal T-cell lymphomas at either localization.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
4/8. Natural killer cell lymphoma of small intestine with features of enteropathy but lack of association with celiac disease.A primary small intestinal natural killer (NK) cell lymphoma with pathologic features of enteropathy but lack of association with celiac disease is reported. A 37-year-old man presented with tarry stool, coffee-ground vomitus, and mild fever. He did not have chronic diarrhea or malabsorption. Segmental resection of the duodenum and jejunum showed multicentric transmural infiltration by medium-sized lymphoma cells expressing CD3, CD8, cytotoxic granules, and Epstein-Barr virus by in situ hybridization. The nontumorous mucosa away from the main tumor revealed enteropathy with villous blunting and increased intraepithelial lymphocytes sharing the same immunophenotype as the lymphoma cells. Both lymphoma and nontumorous areas were germline for T-cell receptor-gamma and immunoglobulin heavy chain gene rearrangement. Serologic test by ELISA was negative for anti-transglutaminase. The patient died of repeated gastrointestinal bleeding and sepsis at 2 months. Differential diagnosis of this unique nasal-type NK-cell lymphoma with enteropathy-associated t-cell lymphoma is discussed.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/8. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma--association with gastrointestinal location and absence of melanocytic differentiation.PURPOSE: Clear cell sarcoma (CCS) usually arises in the lower extremities of young adults and is typically associated with a t(12;22) translocation resulting in the fusion of EWS (EWSR1) with ATF1, a gene encoding a member of the cyclic amp-responsive element binding protein (CREB) family of transcription factors. CCS arising in the gastrointestinal tract is rare and its pathologic and molecular features are not well defined. EXPERIMENTAL DESIGN: We report a novel variant fusion of EWS to CREB1, a gene at 2q32 encoding another CREB family member highly related to ATF1, detected in three women with gastrointestinal CCS. All three cases contained an identical EWS-CREB1 fusion transcript that was shown by reverse transcription-PCR. In two of the cases tested, EWS gene rearrangement was also confirmed by fluorescence in situ hybridization and the EWS-CREB1 genomic junction fragments were isolated by long-range dna PCR. RESULTS: Morphologically, all three tumors lacked melanin pigmentation. By immunohistochemistry, there was a strong and diffuse S100 protein reactivity, whereas all melanocytic markers were negative. Ultrastructurally, two of the cases lacked melanosomes. The melanocyte-specific transcript of MITF was absent in two cases, and only weakly expressed in the third case. The Affymetrix gene expression data available in one case showed lower expression of the melanocytic genes MITF, TYR, and TYRP1, compared with four EWS-ATF1-positive CCSs of non-gastrointestinal origin. CONCLUSIONS: EWS-CREB1 may define a novel subset of CCS that occurs preferentially in the gastrointestinal tract and shows little or no melanocytic differentiation. Thus, evidence of melanocytic lineage or differentiation is not a necessary feature of sarcomas with gene fusions involving CREB family members.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/8. Malignant lymphoma presenting as Kaposi's sarcoma in a homosexual man with the acquired immunodeficiency syndrome.A homosexual man had Kaposi's sarcoma of the skin and lymph nodes. After a brief response to interferon, the patient developed new skin lesions. Massive bleeding in the gastrointestinal tract prompted endoscopy, which showed tumor involvement of the stomach, believed to be Kaposi's sarcoma. At autopsy, a diffuse lymphoma was found involving the skin and gastrointestinal tract, forming collision tumors in regions that contained Kaposi's sarcoma. Lymphomatous tissue, but not uninvolved lymph node or spleen, contained Epstein-Barr virus dna, as shown by dna hybridization studies. Epstein-Barr virus may play a role in the development of lymphoma in immunosuppressed patients. Unusual manifestations of tumors, such as the massive gastrointestinal bleeding seen in this case, may indicate the development of a second neoplasm.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/8. A possible role for Epstein-Barr virus in tumorigenesis after immunosuppression in cases of renal transplantation.Eight secondary malignancies developing after renal transplantation were investigated in terms of a possible role of the Epstein-Barr virus (EBV). In five cases, four gastric cancers and one colonic cancer, the presence of EBV was proven by the polymerase chain reaction (PCR), all four gastric lesions being confirmed to have a massive EBV infection by in situ hybridization. Two cases demonstrated monoclonal infection with EBV, as indicated by a single band of the lymphocyte-defined membrane antigen tandem-repeat gene using PCR, and were immunohistochemically positive for the latent membrane protein 1. Our series suggests that gastrointestinal cancer predominates as a secondary malignancy in states of induced severe immunosuppression, and that EBV may play an important role in tumorigenesis as an oncovirus.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/8. Different patterns of dna copy number changes in gastrointestinal stromal tumors, leiomyomas, and schwannomas.It is not uniformly agreed whether gastrointestinal stromal tumors (GISTs) are phenotypical variants of leiomyomas (cellular leiomyomas) or whether they represent a separate, genotypically definable entity. In an attempt to solve this question, we examined immunohistochemically defined leiomyomas from the esophagus and uterus, gastric schwannomas, and benign gastrointestinal stromal tumors (GIST) by comparative genomic hybridization (CGH). All 14 leiomyomas (nine esophageal, five uterine) were actin- and desmin-positive but negative for CD34 and S100-protein. Changes in dna copy numbers were seen only in three esophageal leiomyomas. Gains were observed in chromosomes 3, 4, 5, 8, and 17, whereas losses were seen in 16p. All schwannomas were positive for S100-protein and negative for actin, desmin, and CD34. In schwannomas, the only change by CGH was a gain in 11q in one case. The benign GISTs, all from the stomach, were positive for CD34 but negative for desmin and S100-protein; two cases were positive for actin. The CGH findings in the GISTs differed markedly from those in leiomyomas and schwannomas. Ten of the 13 cases (77%) showed dna copy number losses in 14q, and additional or other losses were found in eight cases, most often in chromosome 22 (seven cases), 15 (three cases), and 1p (two cases). Furthermore, two of the GISTs showed gains in 5q. These results indicate that phenotypically undifferentiated GISTs are also genetically different from leiomyomas and schwannomas and support their classification apart from leiomyomas.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |