(1/527) Frequent loss of heterozygosity for chromosome 10 in uterine leiomyosarcoma in contrast to leiomyoma.
Distinction of malignant uterine leiomyosarcomas from benign leiomyomas by morphological criteria is not always possible. Leiomyosarcomas typically have complex cytogenetic abnormalities; in contrast, leiomyomas have simple or no cytogenetic abnormalities. To understand better the biological distinction(s) between these tumors, we analyzed two other potential markers of genomic instability, loss of heterozygosity (LOH) and microsatellite instability. We examined archival materials from 16 leiomyosarcomas and 13 benign leiomyomas by polymerase chain reaction for 26 microsatellite polymorphisms. Markers were selected based on previous reports of cytogenetic or molecular genetic abnormalities in leiomyosarcomas or leiomyomas and surveyed chromosomes 7, 9, 10, 11, 12, 14, 15, 16, 18, 21, and X. LOH for markers on chromosomes 15, 18, 21, and X was infrequent in leiomyosarcomas (1 of 6 tumors for each chromosome) and not observed for markers on chromosomes 7, 9, 11, 12, 14, or 16. Interestingly, 8 of 14 (57.2%) informative leiomyosarcomas had LOH for at least one marker on chromosome 10 and involved both chromosomal arms in 45.5% (5 of 11). In contrast to leiomyosarcomas, LOH for chromosome 10 was not found in 13 benign leiomyomas. Microsatellite instability was found infrequently in leiomyosarcomas and not detected in leiomyoma. Clinicopathological features (eg, atypia, necrosis, and clinical outcome) did not appear to correlate with LOH for chromosome 10. In contrast to other chromosomes studied, LOH on chromosome 10 was frequent in leiomyosarcomas and absent in benign leiomyomas. (+info)
(2/527) Morphological, histochemical, immunohistochemical, and ultrastructural characterization of tumors and dysplastic and non-neoplastic lesions arising in BK virus/tat transgenic mice.
To study the role in AIDS pathogenesis of the human immunodeficiency virus type 1 (HIV-1) Tat protein, a transactivator of viral and cellular genes, we generated transgenic mice with a recombinant DNA containing BK virus (BKV) early region and the HIV-1 tat gene, directed by its own promoter-enhancer. DNA hybridization revealed that the transgene is stably maintained in all organs of transgenic mice as a tandem insertion in a number of copies ranging from 5 to 20 per cell. In addition, tat and BKV RNA were expressed in all tissues. Transgenic mice developed three types of lesions: 1) tumors, 2) hyperplastic and dysplastic lesions, and 3) non-neoplastic lesions. Tumors of different histotypes, such as lymphomas, adenocarcinomas of skin glands, leiomyosarcomas, skin squamous cell carcinomas, hepatomas, hepatocarcinomas, and cavernous liver hemangiomas, developed in 29% of transgenic animals. The majority of tumors were malignant, invasive, and producing metastases. Conversely, tumors of only two histotypes (lymphomas and adenocarcinomas of skin glands) appeared in control mice. Hyperplastic and dysplastic lesions were more frequent in transgenic than in control mice and involved the skin or its adnexes, the liver and the rectum, indicating multiple targets for the activity of the transgene. Pyelonephritis, frequently complicated with hydronephrosis, inflammatory eye lesions, and amyloid depositions represented the most frequent non-neoplastic lesions detected in transgenic mice. Many of the pathological findings observed in this animal model are comparable to similar lesions appearing in AIDS patients, suggesting a relevant role for Tat in the pathogenesis of such lesions during the course of AIDS. (+info)
(3/527) Possible role of calponin h1 as a tumor suppressor in human uterine leiomyosarcoma.
BACKGROUND: Calponin h1, a basic actin-binding protein capable of inhibiting smooth muscle contraction, is a constitutive element of smooth muscle cells. However, in leiomyosarcoma (a type of smooth muscle neoplasm of the uterus), reduced expression of calponin h1 is observed, as we have reported previously. In this study, we sought to assess the effects (in vitro and in vivo) of increasing calponin h1 expression in leiomyosarcoma cells. METHODS: A plasmid containing a human calponin h1 complementary DNA and a bacterial neomycin-resistance gene was transfected into the human leiomyosarcoma cell lines SKN and SK-LMS-1 by electroporation. Southern blotting, reverse transcription-polymerase chain reaction analysis, western blotting, and immunohistochemistry were used to confirm DNA transfer and expression of the calponin h1 protein in neomycin-resistant clones. We characterized the morphology of calponin h1-transfected cells, and we evaluated their proliferative activity and tumorigenicity by use of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, an anchorage-independent growth assay, and a nude mouse tumorigenicity assay. RESULTS: The morphology of calponin h1-transfected cells in culture resembled that of cultured normal myometrial smooth muscle cells. With SK-LMS-1 cells, proliferation of calponin h1-transfection cells was reduced to 69% of control; with SKN cells, calponin h1 transfection reduced proliferation to 70% of control. In assays of anchorage-independent growth and in vivo tumorigenicity, both growth and tumorigenicity were statistically significantly reduced in calponin h1-transfected leiomyosarcoma cells. CONCLUSIONS: Calponin h1 may function as a tumor suppressor in leiomyosarcoma. Clinically, transfer of a calponin h1 complementary DNA into poorly differentiated leiomyosarcoma cells may be of potential therapeutic value through induction of a normal, differentiated cellular phenotype. (+info)
(4/527) Cerebral metastasis of a uterine leiomyosarcoma--case report.
A 38-year-old female presented with sudden neurological deterioration 6 years after an operation and chemotherapy for uterine leiomyosarcoma. An extremely rare metastasis of the uterine leiomyosarcoma to the brain was identified and totally resected. Whole brain irradiation (50 Gy) was given. A recurrence of the metastasis was resected 10 weeks later. She ultimately died of a second recurrence. Aggressive surgical management of cerebral metastasis of uterine leiomyosarcoma may achieve an improved outcome. (+info)
(5/527) Leiomyosarcoma of the esophagus in a patient with chagasic megaesophagus: case report and literature review.
Leiomyosarcoma constitutes approximately 0.5% of the malignant neoplasias of the esophagus and its association with megaesophagus has not been described. We report on a case of a woman with dysphagia that was slowly progressive from the age of 19 due to chagasic megaesophagus. The woman was subjected to cardiomyotomy at the age of 49. She presented a rapid worsening of the dysphagia due to leiomyosarcoma at the age of 61, and was subjected to subtotal esophagectomy with cervical esophagogastroplasty. She developed pulmonary and hepatic metastases 14 months after surgery and died six months later. (+info)
(6/527) "Mesenchymal tumor" or "decidual-like reaction"?
For more than 40 yr, an unusual urinary bladder lesion has been known to occur in certain strains of mice, but no consensus has been obtained regarding its etiology, pathogenesis, biology, or classification. The lesion was first assumed to be epithelial and non-neoplastic, then it was called a smooth muscle cell tumor or leiomyosarcoma because of ultrastructural characteristics for smooth muscle cells. Later, the nonspecific term "mesenchymal tumor" was introduced due to histomorphologic differences from all smooth muscle tumors known. Recently, a proposal was made to name it "decidual-like reaction" because of the histomorphologic similarity to the rare spontaneous decidual reaction in the uterus of aging mice. Both lesions are characterized by spindle and large pleomorphic epithelioid cells with large bizarre nuclei; these characteristics mimic anaplasia of malignant tumors and led pathologists to assume a neoplastic nature. The decidual hypothesis is supported by the regular presence of nuclear progesterone receptors, the occasional occurrence of eosinophilic cytoplasmic granules, the rare finding of cells morphologically resembling granulated metrial gland cells (all also observed in the uterine decidual reaction), and the reproducibility through long-term feeding of combinations of estrogens and progestogens. It appears that the new decidual hypothesis can explain many detailed facets of the lesion, with the exception of the reported smooth muscle cell characteristics. The controversy of "mesenchymal tumor versus decidual-like reaction" should be resolved soon, not only as a scientific issue, but also because of consequences for risk assessment. (+info)
(7/527) Correlation between clinicopathological features and karyotype in spindle cell sarcomas. A report of 130 cases from the CHAMP study group.
Soft-tissue tumors have proved to be a fruitful area for the identification of reproducible cytogenetic aberrations, especially among pediatric round-cell sarcomas and lipomatous tumors. Thus far, however, data regarding sarcomas of monomorphic spindle cell type have been limited and somewhat disappointing, with the notable exception of synovial sarcoma. As part of an ongoing international collaborative study, 130 karyotyped spindle-cell sarcomas were reviewed and classified histologically, without knowledge of the clinical and karyotypic data, with the aim of identifying objective correlations between morphology, karyotype, and clinical parameters. Clonal chromosomal abnormalities were identified in 82 cases studied (63%), but only in the group of synovial sarcomas was there clear correlation between the cytogenetic findings, in the form of a consistent t(X;18)(p11;q11), and morphology. Among leiomyosarcomas (41 cases) and malignant peripheral nerve sheath tumors (MPNSTs; 27 cases) as well as in individual examples of rarer entities, there was a general tendency for karyotypic complexity associated with frequent loss or rearrangement of chromosome arms 1p, 10p, 11q, 12q, 17p, and 22q. Rearrangements of 17q (the region of the NF1 gene) were seen in 9/27 (33%) of MPNSTs. Among nine cases of solitary fibrous tumor (in which previous cytogenetic data are very limited) no consistent aberrations were identified. We conclude that, with the exception of synovial sarcoma, most spindle-cell sarcomas share with pleomorphic sarcomas the tendency for karyotypic complexity. There was no indication (in most of these lesions) that detectable cytogenetic aberrations could either facilitate their diagnosis or help to determine prognosis. There is a clear need to further study and understand the significance of multiple chromosomal abnormalities in this group of mesenchymal neoplasms with the particular goal of determining their role in the process of tumor development. (+info)
(8/527) Prognostic significance of bcl-2 expression in leiomyosarcoma of the uterus.
We examined bcl-2 expression as well as p53 expression and mutation in human uterine smooth muscle tumours to determine the influence of bcl-2 expression on prognosis in patients with uterine leiomyosarcomas. bcl-2 protein was expressed in nearly all benign smooth muscle tumours but in only 57% of leiomyosarcomas. Benign smooth muscle tumours were usually negative for p53 protein, but 16 out of 21 (76%) leiomyosarcomas were positive. A p53 gene mutation was detected in nine of the 16 leiomyosarcomas that showed p53-positive staining. A significant positive correlation was observed between p53 mutation and p53 expression, between the number of mitoses and the Ki-67 labelling index, and between clinical stage and p53 mutation. A significant negative correlation was observed between bcl-2 expression and p53 mutation, and between bcl-2 expression and p53 overexpression. Univariate survival analysis revealed that bcl-2 expression, p53 mutation and clinical stage (stage 1 vs stages 2-4) all showed a significant correlation with prognosis. In a multivariate stepwise regression analysis, positive bcl-2 expression and stage 1 disease were the independent predictors of a favourable prognosis. Our results suggest that bcl-2 is frequently expressed in human uterine smooth muscle tumours, and that its expression may correlate with a favourable prognosis in patients with uterine leiomyosarcoma. (+info)