摘要:

From the Department of Cancer Biology, Harvard School of Public Health, and the Department of Ophthalmology, Harvard Medical School, Boston, U.S.A. (D.W.Y.); the Department of Pathology, Harvard Medical School, and the James Homer Wright Pathology Laboratories of Massachusetts General Hospital, Boston. U.S.A. (A.D.T.).

ISSN:1052-9551    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We set out to define the alterations of chromosome 17 in human bladder tumors and to correlate p53 nuclear over-expression with 17p deletions in those neoplasms. We studied 60 bladder tumors by restriction fragment-length polymorphism analysis directed at five different loci on chromosome 17. The same tumors were studied with a panel of mouse monoclonal antibodies (PAb1801, PAb240, and PAb1620) to mutant and wild-type p53 proteins using immunohistochemistry. Deletion of 17p correlated with grade (p = 0.039), stage (p = 0.004). and the presence of vascular invasion (p = 0.056). None of the pathologic parameters correlated with 17q deletions. p53 nuclear overexpression correlated with grade (p = 0.027), stage (p = 0.008), vascular invasion (p = 0.021), and the presence of nodal metastases (p = 0.007). In superficial (Ta) lesions, 17p was not deleted, whereas 557c of T1 and T2-T4 tumors showed a loss of heterozygosity. Mutations of p53 as detected by immunohistochemistry were seen in superficial as well as invasive tumors, whereas loss of heterozygosity was seen only in invasive tumors. A strong correlation was found between the presence of mutation and the loss of heterozygosity of the remaining allele (p = 0.0003). Additional follow-up and further studies are required to better define the role of p53 nuclear overexpression and 17p deletions as markers of tumor progression in human bladder cancer.

ISSN:1052-9551    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Mutations in the p53 tumor suppressor gene occur in >50% of human malignancies, but are exceedingly rare in benign tumors. The malignant potential of fibrous tumors of children may be unpredictable at microscopic examination. We therefore sought to determine whether malignant fibrous tumors could be distinguished from their benign counterparts by the presence of mutations in p53. We screened 27 fibrous tumor samples from 20 young patients. Tumors were classified as benign, borderline, or malignant by conventional microscopic criteria. RNA extracted from each specimen was used as the template for reverse transcription followed by polymerase chain reaction (PCR) amplification, with six pairs of primers covering the whole coding region of the p53 gene. All PCR products were screened for the presence of mutations using single-strand conformation polymorphism analysis. In addition. PCR products encompassing exons 5–9. the sites of the most frequent mutations in human tumors, were sequenced directly. Both methods detected a single point mutation in a highly malignant tumor (malignant fibrous histiocytoma). The mutation was a silent one at codon 36 (CCG-CCA, Pro-Pro). We conclude that p53 mutations are infrequent in childhood fibrous tumors. consistent with previous observations of low malignant potential (<10%) and better prognosis in this tumor group. Therefore, screening for p53 mutations is not a useful prognostic indicator in fibrous tumors with borderline pattern at microscopic examination.

ISSN:1052-9551    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Medulloblastoma (MB), the most common malignant tumor of the CNS in children, bears a loss of the short arm of chromosome 17 in almost half of the cases. The tumor suppressor gene p53 is located on this chromosome and its role in the pathogenesis of this primitive tumor is controversial. Twenty-two MBs were analyzed by single-strand conformation polymorphism (SSCP) of polymerase chain reaction-amplified conserved exons. Fragments displaying a gel mobility shift were subsequently analyzed by direct sequencing. Immunohistochemistry for p53 was performed in all cases; three had cytogenetic analysis. Two cases (9%) were found to harbor a mutation: one homozygous and one heterozygous. The latter showed focal p53 immunostaining. None of the cases with chromosome 17p abnormality by cytogenetic analysis were found to have a mutation in the remaining allele. Loss of heterozygosity (LOH) of 17p, however, was found in four cases (one by SSCP and three by cytogenetic analysis). Together with the homozygous deletion in one case, the overall incidence of p53 allelic involvement in MB is 23% Although LOH for the p53 gene may confer a selective advantage to tumor cells harboring mutations with dominant negative oncogenic effect, the infrequent occurrence of p53 mutations in face of frequent LOH for this gene supports the previously formulated hypothesis of a novel tumor-related locus distal to p53 on chromosome 17p.

ISSN:1052-9551    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The p53 gene mutation pattern was used as a diagnostic marker of multiple and second primary lung carcinomas. Nine cases of multiple carcinoma, which were suspected clinicopathologically to be double or triple primary carcinomas. were examined for p53 protein expression by immunohistochemistry and for genetic abnormality of the p53 gene by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Nine tumors from four cases gave a positive result upon both immunostaining for the p53 protein and PCR-SSCP analysis of the p53 gene. These nine tumors showed different mobility shifts between exons 5 and 8. The four cases were diagnosed genetically as multiple primary carcinomas. To confirm the results of PCR-SSCP analysis, five tumors from two cases that showed different mobility shifts were further analyzed for their nucleotide sequences, and it was found that all of them had point mutations at different codons in exons 5 and 8. These findings suggest that the p53 gene mutation pattern is an effective marker for diagnosis of tumor multiplicity.

ISSN:1052-9551    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Accumulation of p53 protein resulting in levels detectable by immunohistochemistry (IHC) has been proposed as an indicator of mutation of the p53 gene. We have investigated a panel of 23 fresh-frozen breast cancers by IHC (PAb 1801). Southern and Northern blot analysis, and direct sequencing of the mutation hot spot regions (exons 5–8) of the p53 gene. Three tumors (13%) showed an intense nuclear staining in the majority of malignant cells, but only one of these showed a mutation of the p53 gene (codon 237, Arg to His). Furthermore, a mutation (5-bp deletion) was identified in a tumor that showed no p53 immunoreactivity. Our results indicate that accumulation of p53 protein, as detectable by IHC, is not a reliable indicator for p53 gene mutation in human breast cancer.

ISSN:1052-9551    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Formalin-fixed, paraffin-embedded tissue from B-cell malignant lymphomas (26), reactive lymphadenopathies (8), non-B-cell malignancies (5), and atypical lymphoprolifer-ative lesions (7) were analyzed for clonal immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction (PCR), using consensus primers for the variable and joining regions of the gene. By employing a high-resolution gel electrophoresis technique, we were able to demonstrate one or two dominant bands, indicating a clonal population, in 15 of the 23 cases (65%) of B-cell lymphoma in which amplification occurred. Six of six reactive lymph nodes in which amplification occurred produced a multibanded pattern indicative of a polyclonal population. This improved PCR technique allows a clearer distinction between clonal and polyclonal patterns than other previously proposed methods. It also works well in paraffin-embedded tissue and may therefore be a useful adjunct to the diagnostic armamentarium applied to archival material.

ISSN:1052-9551    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We determined the DNA ploidy and the centromeric copy number of chromosomes 7, 12, 18, and X in four cases of ovarian dysgerminoma using DNA flow cytometry and fluorescence in situ hybridization (FISH) with chromosome-specific alpha-satellite probes. The analyses were performed on nuclei isolated from paraffin-embedded tissue. The DNA index of the tumors ranged from 1.75 to 2.08 (near tetraploid). The FISH analysis demonstrated five copies of chromosome 7 and four copies of chromosome 12 in most tumors. The copy number of chromosome 18 ranged from two to four. The X chromosome was present in three copies in most tumors. These data show that the aneuploidy profile of dysgerminoma is similar to that of testicular seminoma. Overrepresentation of chromosomes 7 and 12 and underrepresentation of chromosome 18 are characteristic cytogenetic features of seminoma. Seminoma and dysgerminoma share the same chromosomal marker, an isochromosome i(12p). Our data suggest that these tumors are also characterized by a similar, nonrandom pattern of chromosome gains and losses.

ISSN:1052-9551    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We describe the pathologic, molecular, and clinical features of a 52-year-old man who had a 7-year history of widely disseminated, persistent lymphoid hyperplasia. Exuberant follicular and interfollicular lymphoid hyperplasia with some histologic features of Castleman's disease were present at various times in the submental and cervical lymph nodes, lacrimal and parotid glands, right and left orbits, mediastinum, and hard palate of this patient. Flow cytometric and immunoperoxidase studies of two of the specimens indicated a slight predominance of cells expressing-immunoglobulin light chain. In one specimen, there were clonal rearrangements of DNA coding for immunoglobulin heavy chain and for the T-cell (3-receptor. When DNA from this specimen was also examined by the polymerase chain reaction technique. Epstein-Barr viral DNA was detected. This case suggests that Epstein-Barr virus may be associated with an unusual form of aggressive and persistent lymphoid hyperplasia that contains clonal rearrangements of DNA.

ISSN:1052-9551    

出版商:OVID    

年代:1993

数据来源: OVID