ISSN:0022-3417    

DOI:10.1002/path.1711770102

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

ISSN:0022-3417    

DOI:10.1002/path.1711770103

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractIncreased and disorganised expression of CD44 variant exons has been demonstrated in biopsy samples of several types of human malignancy by many groups. This abnormality can be used to detect exfoliated tumour cells in the urine of bladder cancer patients. The present report demonstrates that the deranged activity of this gene in neoplasia also results in the accumulation of immature mRNA transcripts containing non‐coding sequences (introns) from this gene in cancer tissues and cells. There is simultaneous overexpression of a newly identified 437 bp exon (coding sequence) located in the variably active region of the gene and of many abnormal variant exon combinations. This is the first report describing the specific retention of introns in gene transcripts in clinical diagnotic samples of tumour tissues and cells. The phenomenon was seen repeatedly in samples from cancer patients and in a cancer cell line, and thus could form the basis for a unique new and specific method of cancer diagnosi

ISSN:0022-3417    

DOI:10.1002/path.1711770104

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractBCL‐6 is a novel proto‐oncogene that codes for a zinc‐finger protein sharing homologies with many transcription factors. It has recently been shown that BCL‐6 is involved in chromosome band 3q27 aberrations in non‐Hodgkin's lymphomas (NHLs) and BCL‐6 rearrangements have been detected in 34–45 per cent of diffuse large cell lymphomas with B immunophenotype. We have studied the BCL‐6 gene configuration by Southern blot analysis in 60 cases of B‐cell NHL and in 17 cases of Hodgkin's disease (HD). BCL‐6 was rearranged in 15/46 (32·6 per cent) diffuse B‐large cell lymphomas, mainly with centroblastic morphology, and in 2/11 (18·2 per cent) follicular (centroblastic‐centrocytic) lymphomas. Conversely, all cases of HD, including four cases of lymphocyte predominant, nodular type (nodular paragranuloma), had a germline configuration. These findings confirm that BCL‐6 is rearranged in a significant percentage of diffuse B‐large cell lymphomas, suggesting that this proto‐oncogene might have a pathogenetic role in this subset of NHLs, but our preliminary analysis suggests that BCL‐6 lesions are not involved in the pathogenesis of HD. However, further investigations using more sensitive techniques are r

ISSN:0022-3417    

DOI:10.1002/path.1711770105

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractMDM2 and p53 immunohistochemical protein expression was analysed in lymphocytes and in reactive and neoplastic lymphoid tissue. Phytohaemagglutinin (PHA)‐stimulated lymphocytes displayed MDM2 and p53 co‐expression. In 8 of 8 tonsils, 24 of 24 Hodgkin's disease (HD), and 10 of 24 high‐grade non‐Hodgkin's lymphoma (HG‐NHL) specimens, MDM2 paralleled p53 nuclear expression in non‐tumour and tumour cells. The number of positive cells was greater and the staining intensity was stronger for p53 than for MDM2. In another nine of the 24 HG‐NHL cases studied, dissociated expression was observed, with high p53 expression and very low or absent MDM2 expression. In five cases, both MDM2 and p53 were negative. The eight low‐grade NHL (LG‐NHL) cases were also MDM2‐ and p53‐negative. MDM2 and p53 expression in PHA‐activated lymphocytes and reactive lymphoid tissue is probably an expression of opposing biological signals regulating cell proliferation. Parallel MDM2 and p53 expression in all HD and in 10 out of 24 HG/NHL cases may indicate that this growth suppressive pathway is maintained in those cases. However, dissociated MDM2/p53 expression (nine cases) and the absence of expression of both proteins (five cases) may represent examples of deregulation of this growth control pathway. These findings are in agreement with previousin vitrostudies in cell lines regarding the role of MDM2/p53 interaction in the regulation of growth control and extend this observation to normal lymphocytes and reactive lymphoid tissue, suggesting a possible role for MDM2 deregula

ISSN:0022-3417    

DOI:10.1002/path.1711770106

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractA well‐recognized complication of Sjögren's syndrome (SS) is the development of malignant lymphoma, with a risk 44 times that of the general population. Although a few clinical signs may indicate the onset of lymphoma, there are few reliable laboratory markers which predict the development of neoplasia. A non‐isotopicin situhybridization technique has been applied to routinely processed labial salivary gland (LSG) biopsies of patients under investigation for SS. Serial sections of 70 LSGs were examined for a κ and λ immunoglobulin light chain mRNA using digoxigenin‐labelled oligonucleotide probes. As controls, 39 biopsies from non‐SS‐associated sialadenitis were also examined. Sections were analysed using computer‐assisted quantification to determine the percentage of κ‐expressing cells in each case. The range of κ expression in the SS group was 24·1–93·4 per cent and in the non‐SS group 48·3–75·4 per cent. Light chain restriction was found in 13/70 (18·6 per cent) cases from the SS group but in no cases of the control group. Of the SS cases showing restriction, 4/13 (30·7 per cent) have subsequently developed extrasalivary gland lymphoma. Two patients not showing light chain restriction in LSG have subsequently developed lymphoma. The positive predictive value of this test to identify patients at risk of lymphoma was 30·7 per cent with a detection rate (sensitivity) of 66·47 per cent and a false‐positive rate of 14·1 per cent (specificity 85·9 per cent). This study has identified a high prevalence of light chain restriction in labial gland biopsies of patients with SS and provides objective quantitative criteria to identify those patients at

ISSN:0022-3417    

DOI:10.1002/path.1711770107

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractHairy cell leukaemia (HCL) is a chronic lymphoproliferative disease of B‐cell lineage. One of the peculiar immunophenotypic markers is the strong expression of the p55 chain of the interleukin‐2 receptor (IL2R), recognized by anti‐CD25 (or anti‐Tac) monoclonal antibody. However, it is known that in rare cases CD25 may not be detectable, even when variant forms of HCL are excluded. The possibility has not been investigated that in these situations CD25 is present in the cytoplasm of the neoplastic cells. This paper describes a case in which the clinical, histological, and electron microscopic features were consistent with a typical HCL. Immunophenotype analysis showed the whole spectrum of markers of HCL, except for the expression of IL2R. The soluble form of the molecule was, however, increased in the patient's serum. Cytospin staining of the neoplastic B cells with anti‐CD25 clearly demonstrated the presence of IL2R in the cytoplasm of hairy cells. When the cells were cultivatedin vitroin the presence of interferon‐α2b, CD25 was detectable at the membrane level. These findings suggest that at least some cases of CD25‐negative HCL may express cy

ISSN:0022-3417    

DOI:10.1002/path.1711770108

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe expression of bcl‐2 protein was analysed immunohistochemically in 202 female breast carcinomas. The intensity of bcl‐2 expression was inversely related to tumour grade (P<0·0001), tumor necrosis (P<0·0001), mitotic index (P<0·0001), oestrogen receptor content (P<0·0001), progesterone receptor content (P=0·0007), S‐phase fraction (P=0·00047), and apoptotic index (P=0·087). A high fraction of bcl‐2‐positive cells was related to ductal or lobular type (P=0·03) and slight nuclear pleomorphism (P=0·03). Heterogeneous expression of bcl‐2 protein was associated with high grade (P=0·02), severe nuclear pleomorphism (P=0·02), DNA aneuploidy (P=0·018), high S‐phase fraction (P=0·05), and early metastasis (P=0·03). Intense expression of bcl‐2 protein was significantly related to favourable outcome in the entire cohort (P=0·0013), as well as in axillary lymph node‐negative (ANN) tumours (P=0·0124). Long recurrence‐free periods in the entire cohort (P=0·037) and in ANN tumours (P=0·08) were confined to cases with intense expression of bcl‐2 protein. In multivariate analysis, bcl‐2 expression had no independent prognostic value in the entire cohort or in axillary lymph node‐negative breast carcinomas, whereas it was a weak independent prognostic factor in axi

ISSN:0022-3417    

DOI:10.1002/path.1711770109

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe growth of newly formed vessels, or neoangiogenesis, represents an important step in both physiological and pathological situations: in particular, tumour growth and metastasis require angiogenesis. Microvessel count (MC), which represents a measure of tumour angiogenesis, has been associated with metastatic spread in cutaneous, mammary, prostatic, head and neck, and early‐stage lung cancer. In this study, the role of tumour angiogenesis as a prognostic indicator was examined in 253 primary non‐small cell lung cancer (NSCLC) patients. Microvessels were counted by highlighting endothelial cells with anti‐Factor VIII monoclonal antibody (MAb) in methacarn‐fixed tumour samples. In univariat analysis, MC (P<0·000001), sex (P=0·0036), histotype (P<0·014), tumour status (P<0·007), and vessel invasion (P<0·019) were significantly related to hilar and/or mediastinal nodal involvement. However, in the stepwise logistic regression analysis, MC (P25 vessels/field) were significantly associated with increased death risk (log‐rank testP=0·00067; Cox's testP=0·00046; Gehan's Wilcoxon testP=0·00108). In 94 patients, the development of metastatic disease during follow‐up was significantly related to MC. Indeed, patients who developed metastasis during follow‐up showed a higher MC, either as a dichotomous (P=0·01) or as a continuous (P=0·003) variable, than patients who had developed no metastasis at the time of the analysis. Moreover, in the stepwise logistic regression analysis, MC retained the most important influence on distant metastases. Microvessel count, as a method for the quantitation of tumour angiogenesis, has an important prognostic role in non

ISSN:0022-3417    

DOI:10.1002/path.1711770110

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractMutation and overexpression of p53 have been described in uterine malignant mixed Müllerian tumours and in endometrial adenocarcinoma, where it has been associated with a poor prognosis. This study examines p53 expression and mutation of the p53 gene in benign and malignant smooth muscle tumours of the uterine corpus. p53 expression was evaluated by immunohistochemistry in formalin‐fixed, paraffin‐embedded tissue from 23 leiomyo‐sarcomas, 10 tumours of uncertain malignant potential (TUMPs), and 18 leiomyomas. Single‐stranded conformational polymorphism, (SSCP) analysis of exons 5–8 of the p53 gene was performed on 13 leiomyosarcomas, nine TUMPs, and eight leiomyomas. With microwave antigen retrieval, p53 immunoreactivity was seen in 13/23 leiomyosarcomas, 6/10 TUMPs, and 1/18 leiomyomas. Normal myometrium was unstained. In the absence of microwave treatment, staining was abolished in three leiomyosarcomas, all immunoreactive TUMPs, and the single positive leiomyoma. SSCP analysis revealed mutation in three leiomyosarcomas. There was one mutation in exon 5 in a case with positive immunohistochemistry. Two cases with negative staining showed mutation, one in exon 7 and one in exon 8. Mutation was present in exon 7 in 4/9 and in exon 6 in 1/9 TUMPs. All of these cases showed positive immunohistochemistry. There was no significant difference in outcome between cases with and without positive immunohistochemistry. p53 expression is seen in a significant proportion of uterine leiomyosarcomas. Microwave antigen retrieval increases the proportion of positive cases and also results in positive staining in TUMPs. Mutation of the p53 gene occurs in only a minority of leiomyosarcomas and in a significant proportion of TUMPs. Positive immunohistochemistry does not, however, correlate with the presence of mutation and other factors may be responsible for p53 detection in

ISSN:0022-3417    

DOI:10.1002/path.1711770111

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY