ISSN:0022-3417    

DOI:10.1002/path.1711750202

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

ISSN:0022-3417    

DOI:10.1002/path.1711750203

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractAccumulation of p53 protein was determined by immunohistochemisty in archival material of biopsy specimens from 102 patients with Barrett's oesophagus with different grades of dysplasia, in 24 oesophageal adenocarcinomas associated with Barrett's oesophagus, and in 23 cases of metaplatic epithelium adjacent to these carcinomas. Immunostaining for the p53 protein was found in 23/102 (23 per cent) cases of the Barrett's oesophagus biopsies and in 12/23 (52 per cent) cases of Barrett's oesophagus adjacent to adenocarcinoma. Significant correlations were found between the grade of dysplasia and p53 immunoreactivity in both Barrett's biopsies without adenocarcinoma (P<0.001) and Barrett's oesophagus adjacent to adenocarcinoma (P<0.05). In the adenocarcinomas, intense nuclear immunohistochemical staining for p53 was diffusely or focally present in 20/24 (83 per cent) of the specimens. In Barrett's oesophagus, p53 is a progression marker with high expression in high‐grade dysplasia (89 per cent) and adenocarcinoma (83 per cent

ISSN:0022-3417    

DOI:10.1002/path.1711750204

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

Abstractp53 expression has been examined in 89 squamous cell carcinomas of the larynx (34 glottic, 28 supraglottic, 18 transglottic, 8 pyriform sinus, and 1 subglottic) obtained from 88 patients surgically treated in our centre. In addition, 59 laryngeal samples including normal respiratory epithelium and non‐invasive squamous cell lesions were also tested. Frozen sections were immunostained with PAb 1801 and the results were correlated with pathological features, DNA ploidy and S‐phase of the tumours, disease‐free interval, and survival of the patients. p53 immunoreactivity was observed in 57 (64 per cent) carcinomas. None of the eight samples of normal respiratory epithelium was positive. p53‐positive cells were seen in 8 of 23 (35 per cent) squamous cell metaplasias, 6 of 19 (32 per cent) low‐grade dysplasias and 5 of 10 (50 per cent) high‐grade dysplasias. No correlation was found between p53 expression in carcinomas and their clinical and pathological characteristics, DNA ploidy, or proliferative activity. Neither disease‐free nor overall survival showed differences between p53‐positive and p53‐negative cases. These findings indicate that p53 may play a role in an early stage of malignant transformation of a subset of squamous cell carcinomas of the larynx, but seems not to be associated with further progressi

ISSN:0022-3417    

DOI:10.1002/path.1711750205

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractExpression of the p53 protein can be detected by immunohistochemistry in Reed‐Sternberg (RS) cells, the presumed neoplastic component of Hodgkin's disease (HD) lesions. At present, there is no clear molecular evidence that p53 positive immunostaining in HD correlates with the presence of mutations or other structural alterations of the p53 gene. To address this question, 49 cases of HD have been investigated for p53 expression by immuno‐histochemistry, using the DO1 monoclonal antibody on paraffin sections. Thirty‐seven out of 49 cases (75 per cent) exhibited positive immunostainining restricted to RS cells and variants. Among these 37 positive cases, ten cases were selected on the basis of a rich content of RS cells showing virtually 100 per cent DO1 positivity. A PCR‐mismatch strategy was chosen for the detection of p53 mutations. The threshold level of sensitivity was assessed on positive cell‐line controls. A proportion of 10–15 per cent p53 mutated cells mixed in a normal population could be identified. Total genomic DNA was extracted from the ten selected HD cases and PCR amplification of exons 5–8 of the p53 gene was performed. Heteroduplex mismatch analysis revealed no structural alterations of the p53 gene in any case. In view of these findings, it appears unlikely that the sensitivity of the method by itself can fully explain the negative results, although this possibility cannot be completely ruled out. Thus, it is conceivable that p53 positive immunostaining in HD may not necessarily imply genomic alterations in the classic ‘hot spot’ regions and may be related to another mechanism of p53 prot

ISSN:0022-3417    

DOI:10.1002/path.1711750206

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractLoss of heterozygosity (LOH) at loci reported to show allele loss in invasive breast cancers was examined in ductalin situcarcinomas of the breast using polymorphic short tandem repeats and the polymerase chain reaction (PCR). LOH was detected at all loci examined in at least 11 per cent of the samples examined. The proportion of cases ofin situcarcinoma showing LOH at these loci was similar to that previously reported in invasive cancers. Cases of purein situcancer without an invasive component exhibited an overall lower frequency of allele loss. LOH at more than one locus was observed in some intraductal cancers. In a small number of cases, LOH was present in the invasive but not in the intraductal component of the tumour, suggesting that mutation at the locus concerned was associated with development of invasive behaviour.

ISSN:0022-3417    

DOI:10.1002/path.1711750207

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractArchival biopsy specimens from transitional cell bladder tumours (n=185) were analysed immunohistochemically for expression of c‐mycprotein. The results were compared with compared with histopathological and clinical parameters and survival. Forty‐three per cent of the tumours were negative for c‐mycprotein and weak, moderate, or strong cytoplasmic expression was found in 34, 14, and 9 per cent of cases, respectively. Nuclear positivity for c‐mycprotein was detected in 35 per cent of tumours and nuclear opositivity was related to overexpression ofc‐erbB‐2 (P=0.01) and a high proportion of nuclei were also positive for p53 oncoprotein (p<0.05). Cytoplasmic expression of c‐mycprotein was related to histological grade (P=0.005), papillary status (P=0.007), the S‐phase fraction (P=0.008), the mitotic index (P=0.021), overexpression of epidermal growth factor receptor (P=0.045), andc‐erbB‐2 (P=0.17). Expression of c‐mycprotein was not significantly related to the progression of tumours and it had no prognostic value in survival analysis. Independent predictors were the T‐category (P<0.001), papillary status. (P=0.001), and S‐phase fraction (P=0.061). The results show that while c‐mycgene product participates in growth regulation of human bladder cancer cells, it has no independ

ISSN:0022-3417    

DOI:10.1002/path.1711750208

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractAmplification of theMDM2gene, which maps to chromosome band 12q13 and encodes a p53‐binding protein, may result in functional inactivation of p53 and has been observed in various bone and soft tissue sarcomas. Published studies have included few cases of Ewing's sarcoma (ES) or peripheral neuroectodermal tumour (PNET), a tumour group in which alterations of the p53 pathway have so far not been extensively studied. We examined two ES cell lines, RD‐ES and SK‐ES‐1, and 30 specimens from 27 patients (24 ES, 6 PNET; 19 primary, 4 local recurrence, 7 metastasis) forMDM2gene amplification by Southern blot analysis. All 30 clinical specimens had been confirmed to contain sufficient ES/PNET DNA by the demonstration of a rearrangement of the t(11;22)‐associatedEWSgene using anEWScDNA probe on the same blots.MDM2gene amplification was detected in 3 of 30 specimens (10 per cent), including two ES and one PNET, but in neither of the cell lines. The three cases with amplification were morphologically typical primary tumours. Two of the three cases also showed co‐amplification of theCDK4gene, which endoces a cyclin‐dependent kinase and also maps to band 12q13. Clinically, all three cases had metastatic disease at diagnosis, compared with only 1 of 15MDM2‐negative cases where the primary tumour was studied. The difference was statistically significant (P=0.005), suggesting an association ofMDM2amplification with advanced stage. Further accural and multivariate analysis of ES/PNET cases withMDM2gene amplification will be necessary to confirm the clinical significance of these findings. The results suggest that the prevalence ofMDM2gene amplification in ES/PNET is comparable to other sarcomas, and implicate dysfunction of the p53 pathway in a subset of ES/PNET. The biological significance ofCDK4co‐amplification remains

ISSN:0022-3417    

DOI:10.1002/path.1711750209

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractAnin situhybridization (ISH) study on paraffin sections of 13 malignant mesotheliomas was performed to detect numerical chromosomal aberrations with biotin‐labelled DNA probes specific for the centromeric regions of chromosomes 1, 3, 6, 7, 11, and 17. All chromosomes contributed to numerical changes, which can be summarized as follows: first, a monosomy for chromosome 6 was found in one case; second, in five cases a trisomy for at least one chromosome was detected; and third, in seven cases a pentasomy or a higher polysomy was found for at least one chromosome. Although these data have to be confirmed on a larger group of patients, survival analysis of this group showed no significant difference between the first and second groups taken together and the third group. In this study no specific numerical chromosomal aberrations were identified. Nevertheless, numerical gains appear to be more frequent than has previously been shown by karyotype analysi

ISSN:0022-3417    

DOI:10.1002/path.1711750210

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to evaluate the distribution of parathyroid hormone‐related peptide (PTHrP) in human thyroid tissues. The presence of PTHrP was studied immunohistochemically in 107 consecutive patients with human thyroid tumours. PTHrP expression was revealed in 97.6 per cent of carcinomas, but not in paranodal normal thyroid epithelial cells. Although there were no differences in the incidence of PTHrP positivity among papillary, follicular, and anaplastic carcinoma cases, PTHrP expression levels were correlated with the growth pattern of thyroid cancer. Strong immunopositivity was detected in 67.3 per cent of papillary growth tissues in papillary carcinomas. A tissue growth pattern consisting of colloid‐absent follicles had a high incidence of strong immunopositivity irrespective of the histological type of tumour. Anaplastic carcinoma without colloid production also showed strong immunoreactivity in all cases. In contrast, a growth pattern of colloid‐rich follicles did not show strong immunopositivity in either papillary or follicular carcinomas. Follicular adenomas showed positive immunostaining in only one case, and no adenomatous goitres showed PTHrP antigens.In situhybridization and reverse transcription‐polymerase chain reaction (RT‐PCR) revealed strong PTHrP mRNA in thyroid cancer tissues, but not in normal thyroid tissues. PTHrP expression was not associated with metastasis, calcification, or hypercalcaemia in thyroid cancers. These results suggest that the expression of PTHrP in human thyroids is closely related to the malignant alteration of normal thyroid epithelial cells, especially in the growth pattern of thyroid carcinom

ISSN:0022-3417    

DOI:10.1002/path.1711750211

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY