1/9. Clonal analysis of a case of multifocal oesophageal (Barrett's) adenocarcinoma by comparative genomic hybridization.Oesophageal adenocarcinomas arising in Barrett's epithelium occasionally present as multiple lesions. This could be due to either a multifocal presentation of the same tumour, or different neoplasms arising simultaneously in a dysplastic Barrett's oesophagus ('field cancerization'). This is a report of the genetic analysis of multiple neoplastic sites in a Barrett's oesophagus with an extensive area of dysplasia. In addition, the dysplastic Barrett's epithelium was evaluated. For the genetic screening, comparative genomic hybridization (CGH) allowed evaluation of the whole genome of each specimen. Five cancerous regions were selected and subsequently dissected from paraffin-embedded tissue blocks. The use of archival materials enabled a targeted collection of representative tumour locations. Multiple genetic aberrations were detected by CGH in all cancer sites. Losses on 3p, 4, 7q, 18q, and Y, as well as gains on 8q, 9q, 12p, 13q, 17q, 20p and X, were found in each specimen. In four out of the five lesions, simultaneous losses on 9p, 15q, and 16q, with concomitant gains on 5p, 7q, and 10p, were disclosed by CGH. Adjacent high-grade dysplastic Barrett's mucosa shared the losses on 3p, 4, 7q, 9p, 18, and Y, as well as the gains on 5p, 7q, 13q, 17q, and X, thereby confirming its precursor status. Within this single and rare case of multifocal Barrett's adenocarcinoma, a monoclonal genotype was present. This must have been caused by an extensive outgrowth of a single tumour.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/9. Deletion of the NF2 region in both meningioma and juxtaposed meningioangiomatosis: case report supporting a neoplastic relationship.We report a case of juxtaposed atypical meningioma and meningioangiomatosis (MA) in an 8-year-old boy with no clinical stigmata or family history of neurofibromatosis. We studied the proliferative activity and genetic changes in the two lesions in an attempt to define their biologic and pathogenetic relationships. The MIB-1 index was 11% in the meningioma and <1% in the MA, indicating increased proliferative activity in the meningioma. fluorescence in situ hybridization was done for two chromosomal regions commonly deleted in meningiomas. There was loss of the neurofibromatosis 2 locus (22q12) in both the meningioma and MA. Conversely, the region of 1p32 was not deleted. Our results indicate that both the meningioma and MA arose from the same clonal process, with the meningioma probably undergoing additional, but undefined, genetic alterations that confer upon it a more proliferative potential. This loss of 22q12 in the MA raises doubt about the presumed hamartomatous nature of MA.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
3/9. Using fluorescence-activated cell sorting followed by fluorescence in situ hybridization to study lineage relationships: the 8;21 translocation is present in neutrophils but not monocytes in a patient with severe congenital neutropenia and a granulocyte colony-stimulating factor-responsive clonal abnormality.Severe congenital neutropenia (Kostmann syndrome) is a disorder that presents in the neonatal period, but predisposes to leukemia later in life. This report describes a 4-y-old female with a history of severe congenital neutropenia, who developed a clonal abnormality associated with the translocation (7;21;8) (q32;q22;q22) (AML-1/ETO). She had circulating peripheral blasts and bone marrow blast counts as high as 64% when she received recombinant granulocyte colony-stimulating factor (rG-CSF). Her marrow blasts decreased to 4-20% when rG-CSF was discontinued. fluorescence in situ hybridization analysis was performed on bone marrow cell populations sorted by flow cytometry to determine which cell populations had the AML-1/ETO translocation. The translocation was found in mature neutrophils and blasts, but not in monocytes, lymphocytes or stem cells. CONCLUSION: These findings suggest that the translocation occurred in a neutrophil progenitor, past the point in ontogeny where monocytes and neutrophils separate. The techniques described may be useful in understanding lineage relationships and leukemogenesis in other clonal abnormalities associated with myelodysplasia and leukemia.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/9. Genetic evaluation of the dysplasia-carcinoma sequence in chronic viral liver disease: a detailed analysis of two cases and a review of the literature.Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies, especially in Asia and africa, but also in the western world its incidence is increasing. HCC is a complication of chronic liver disease with cirrhosis as the most important risk factor. Viral co-pathogenesis due to hepatitis b virus (HBV) and hepatitis c virus (HCV) infection seems to be an important factor in the development of HCC. Curative therapy is often not possible due to the late detection of HCC. Thus, it is attractive to find parameters which predict malignant transformation in HBV- and HCV-infected livers. In the past decade, preneoplastic lesions, i.e. dysplastic foci or nodules, have gained interest as possible markers for imminent malignancy. Noteworthy, dysplastic liver lesions are increasingly detected by imaging techniques. We describe here two cases of chronic viral liver disease, one HBV-and one HCV-related, in which dysplastic lesions were present adjacent to HCC. In the HBV case, a (smaller) satellite of HCC was present as well. The neoplastic specimens were investigated by comparative genomic hybridization (CGH) and in situ hybridization (ISH). Both methods revealed multiple genetic alterations in the HCCs. The genetic patterns of the HBV-related HCC and the satellite tumor showed many shared alterations suggesting a clonal relationship. A subset of genetic changes were already present in dysplasias illustrating their preneoplastic nature. Surrounding liver cirrhosis samples did not display chromosomal aberrations. A literature survey illustrates the relative paucity of information concerning genetic alterations in preneoplastic liver lesions. However, all the data strongly suggests a role for liver cell dysplasia as a precursor condition of liver cell cancer.- - - - - - - - - - ranking = 0.4keywords = hybridization (Clic here for more details about this article) |
5/9. Molecular evidence for progression of nephrogenic metaplasia of the urinary bladder to clear cell adenocarcinoma.Nephrogenic metaplasia or nephrogenic adenoma of the urinary tract may present a diagnostic challenge in surgical pathology practice. Previous case reports suggest the possibility of nephrogenic metaplasia progressing to clear cell adenocarcinoma, but a malignant potential of nephrogenic metaplasia is generally not acknowledged. A case of a 70-year-old female patient with multiple recurrences of nephrogenic metaplasia of the urinary bladder and subsequent development of clear cell adenocarcinoma is described. Immunohistochemical studies help to differentiate the 2 entities. Results of molecular studies, particularly comparative genomic hybridization analysis, suggest clonal evolution of nephrogenic metaplasia to clear cell adenocarcinoma in this case.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
6/9. Study of preneoplastic changes of liver cells by immunohistochemical and molecular hybridization techniques.The status of hepatitis b virus dna was investigated by in situ hybridization in multifocal areas of a noncancerous hepatitis b virus-associated cirrhosis. This liver exhibited a marked degree of dysplasia and adenomatous hyperplasia. The results of these studies were correlated with the histopathology and immunohistochemical stains for hepatitis B core and surface antigens. There was clear evidence of a marked reduction to absence of hepatitis B viral dna by in situ hybridization and absence of HBc and HBsAg in the foci of liver cell dysplasia and adenomatous hyperplasia. These results support the hypothesis that liver cell dysplasia and adenomatous hyperplasia are preneoplastic in nature.- - - - - - - - - - ranking = 1.2keywords = hybridization (Clic here for more details about this article) |
7/9. Persistent active Epstein-Barr virus infection and atypical lymphoproliferation. Report of two cases.Two cases of what is apparently Epstein-Barr virus (EBV)-associated atypical lymphoproliferation which clinically suggested malignant lymphoma are discussed. Immunohistology revealed polyclonal T- and B-cell proliferation resembling progressive infectious mononucleosis. Giant cell formation and marked plasmacytosis was suggestive of Hodgkin's disease. EBV serology was initially not diagnostic, but during the course of the disease, elevated titers against early antigens and EBV-associated nuclear antigen suggested virus replication. EBV dna was demonstrated in lymphoid cells of both cases by in situ hybridization. One case progressed to overt monoclonal B-cell malignant lymphoma. Atypical polyclonal lymphoproliferation in persistent active EBV infection may thus be considered a prelymphomatous condition.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
8/9. Continuity of human papillomavirus (HPV) type between neoplastic precursors and invasive cervical carcinoma. An in situ hybridization study.infection by the human papillomaviruses (HPV) represents an important risk factor in squamous lesions of various sites. More recently, data suggest that the glandular components of some tumors may also contain human papillomaviruses. This association may implicate HPVs in the genesis of these lesions as well. We present a longitudinal in situ hybridization study of HPV expression within a single patient, showing viral mRNA in squamous dysplasia, squamous and adenocarcinoma in situ, and in invasive adenosquamous carcinoma. There was continuity of the viral type (HPV 16) in the preinvasive and invasive portions of the lesions, and HPV mRNA was clearly demonstrable in the glandular components. The case illustrates the utility of in situ hybridization for the microscopic localization of viral gene expression, in addition to providing information about the viral type and perhaps the biologic potential of the lesion.- - - - - - - - - - ranking = 1.2keywords = hybridization (Clic here for more details about this article) |
9/9. Characterization of a human papillomavirus from epidermodysplasia verruciformis lesions of a patient from Upper-volta.A case of epidermodysplasia verruciformis in a patient from Upper-Volta is described. Slightly elevated, flat warts were observed on hands, feet, arms and legs, and pityriasis versicolor-like lesions were found mainly on the trunk. The patient showed no malignant tumors. Histological examination revealed hyperkeratosis, granulosis and moderate acanthosis with large, foamy, basophilic keratinocytes in stratum granulosum and stratum spinosum. Papillomavirus particles could be prepared from these lesions and were differentiated from known papillomavirus types by immune electron microscopy with monospecific antisera and by dna-dna hybridization. The viral dna was characterized by cleavage with several restriction endonucleases and a physical map of the resulting fragments was established. The virus is designated as HPV 8. Preliminary seroepidemiologic studies with human sera indicate a rather wide distribution of HPV 8. Blot hybridization of dna from human carcinomas with 32P-labelled virus dna detected no HPV 8-specific sequences.- - - - - - - - - - ranking = 0.4keywords = hybridization (Clic here for more details about this article) |