Clinical molecular pathology最新文献

{"title":"Tumour infiltrating lymphocytes: insights into tumour immunology and potential therapeutic implications.","authors":"K F Yoong, D H Adams","doi":"10.1136/mp.49.5.m256","DOIUrl":"https://doi.org/10.1136/mp.49.5.m256","url":null,"abstract":"","PeriodicalId":87395,"journal":{"name":"Clinical molecular pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.49.5.m256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26022025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amphotericin B induced abnormalities in human platelets.","authors":"K B Pastakia,&nbsp;N E Brownson,&nbsp;D A Terle,&nbsp;B J Poindexter","doi":"10.1136/mp.49.5.m301","DOIUrl":"https://doi.org/10.1136/mp.49.5.m301","url":null,"abstract":"<p><p>Aims-To investigate in vitro the effect of amphotericin B on platelets in order to understand poor platelet recovery in patients receiving platelet transfusions and amphotericin B simultaneously.Methods-Washed platelets were isolated from platelet concentrates and exposed to amphotericin B (4 mug/ml) for one hour. Platelet function was assessed by aggregation response to thrombin (0-0.6 U/ml), serotonin release, response to hypotonic stress, and mean platelet volume. The expression of surface membrane glycoprotein (GP) Ib-IX complex, GPIIb-IIIa complex and CD62P (P-selectin) was examined by flow cytometry using fluorescence labelled monoclonal antibodies. Heterotypic cell adhesion was measured in amphotericin B treated platelets coincubated with isolated, autologous polymorphonuclear leucocytes (PMN) by flow cytometric analysis.Results-Amphotericin B induced platelet dysfunction. The rate of aggregation by thrombin, serotonin uptake and thrombin induced release of serotonin, and the response of platelets to hypotonic stress were inhibited. There was up to a two-fold increase in the mean platelet volume. The expression of platelet surface GPIb-IX and GPIIb-IIIa was not affected. P-selectin, normally expressed only on the surface of activated platelets, was also expressed on unactivated platelets. Amphotericin B increased platelet adherence to PMN and the number of platelets bound per PMN.Conclusions-In vitro, amphotericin B induces P-selectin expression on the surface of unactivated platelets and increases platelet adhesion to PMN, which is exacerbated by storage. Platelet dysfunction resulting from exposure to amphotericin B may contribute to poor platelet recovery in vivo when amphotericin B is administered concomitantly with platelet transfusion.</p>","PeriodicalId":87395,"journal":{"name":"Clinical molecular pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.49.5.m301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26020849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of intra-tumoral karyotypic heterogeneity by interphase cytogenetics in paraffin wax sections.","authors":"S A Southern,&nbsp;C S Herrington","doi":"10.1136/mp.49.5.m283","DOIUrl":"https://doi.org/10.1136/mp.49.5.m283","url":null,"abstract":"<p><p>Aim-To analyse the effect of sectioning on the assessment of karyotypic heterogeneity by interphase cytogenetics in paraffin wax embedded normal squamous epithelium and to apply the principles derived to invasive cervical carcinoma.Methods-Normal male (n = 5) and female (n = 5) squamous epithelia were hybridised with peri-centromeric repeat probes specific for chromosomes X (DXZ1) and 17 (D17Z1) individually and in combination to assess the effect of sectioning on mono-, di-, tri-, and tetrasomic populations. Section thickness, interobserver variation and variation between different areas of the epithelium were evaluated. Invasive squamous carcinomas of the cervix (n = 5) were then hybridised with the DXZ1 probe and intratumoral heterogeneity was assessed by comparison of signal distributions obtained from different areas.Results-The optimum section thickness for the assessment of normal epithelium was 6 mum. Variation in the expected signal number in the range 1-4 did not introduce artefactual heterogeneity at this section thickness. The sensitivity of this approach for the detection of minor subpopulations was calculated to be 13-16%, 17-18% and 10-11% for mono-, tri- and tetrasomic populations, respectively. Karyotypic heterogeneity was detected in two of the five tumours and, in one case where the populations where clustered morphologically, a minor population representing 18% was identified.Conclusions-Interphase cytogenetic analysis of sections from paraffin wax embedded material can be used for the detection of minor subpopulations in tumours. This approach will be of particular value in the assessment of the relation between human papillomavirus infection and tumour karyotype and in the analysis of intraepithelial neoplasia.</p>","PeriodicalId":87395,"journal":{"name":"Clinical molecular pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.49.5.m283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26022028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p53 protein expression in non-Hodgkin's lymphoma. Comparative study with the wild type p53 induced proteins mdm2 and p21/waf1.","authors":"M Tzardi,&nbsp;C Kouvidou,&nbsp;I Panayiotides,&nbsp;K Stefanaki,&nbsp;D Rontogianni,&nbsp;E Zois,&nbsp;K Koutsoubi,&nbsp;G Eliopoulos,&nbsp;G Delides,&nbsp;P Kanavaros","doi":"10.1136/mp.49.5.m278","DOIUrl":"https://doi.org/10.1136/mp.49.5.m278","url":null,"abstract":"<p><p>Aims-To investigate the pattern of expression of p53 protein and two wild type p53 induced proteins (mdm2 and p21/waf1) as an indirect way of assessing p53 gene status in non-Hodgkin's lymphoma.Methods-Formalin fixed, paraffin wax embedded tissue from 87 cases of nodal non-Hodgkin's lymphoma, comprising 52 high grade and 35 low grade tumours, was stained by immunohistochemistry for p53, mdm2 and p21/waf1 proteins.Results-p53, mdm2 and waf1/p21 proteins were expressed in 36/52, 21/52 and 31/52 high grade and 3/35, 21/35 and 3/35 low grade non-Hodgkin's lymphomas, respectively. Parallel p53/mdm2 protein expression was found in 23 cases (21 high grade and two low grade). These 23 cases were also positive for p21/waf1 protein expression. Discordant p53 positive/mdm2 negative protein expression was found in 16 cases (15 high grade and one low grade). Eleven (10 high grade and one low grade) of these 16 cases were p21/waf1 positive and the remaining five high grade non-Hodgkin's lymphomas were p21/waf1 negative. Mdm2 and p21/waf1 proteins were not expressed in the absence of p53 protein expression.Conclusions-p53, mdm2 and waf1/p21 protein expression is more frequently associated with aggressive histotypes of non-Hodgkin's lymphoma. Parallel expression of p53, mdm2 and p21 proteins may represent non-Hodgkin's lymphomas with a wild type p53 gene as mdm2 and p21 proteins can be induced by the wild type gene. In these cases p53 protein expression may result from stabilisation via complex formation with the mdm2 protein. This could be important in the pathogenesis of these cases as mdm2 may deregulate the p53 dependent growth suppressive pathway. Discordant p53 positive/mdm2 negative/p21 negative protein expression may represent non-Hodgkin's lymphoma with p53 gene mutations unable to activate expression of mdm2 and p21 proteins. Non-Hodgkin's lymphoma with p53 positive/mdm2 negative/p21 positive protein expression may have either wild type p53 with deregulated mdm2 gene expression or mutated p53 gene with p53 independent p21 expression.</p>","PeriodicalId":87395,"journal":{"name":"Clinical molecular pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.49.5.m278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26022027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased expression of CD44v6 in endocrine pancreatic tumours but not in midgut carcinoid tumours.","authors":"B Terris,&nbsp;J F Fléjou,&nbsp;S Dubois,&nbsp;P Ruszniewski,&nbsp;J Y Scoazec,&nbsp;J Belghiti,&nbsp;F Potet,&nbsp;P Bernades,&nbsp;M Mignon,&nbsp;D Hénin","doi":"10.1136/mp.49.4.m203","DOIUrl":"https://doi.org/10.1136/mp.49.4.m203","url":null,"abstract":"<p><p>Aims/background-To analyse the different isoforms of CD44 in various types of endocrine pancreatic and gut carcinoid tumours and to investigate the relation between their expression and tumour dissemination. This study was prompted by the recent observation that inappropriate splicing of the CD44 gene was correlated with tumour progression and metastasis formation in a number of human cancers.Methods-Expression of CD44 isoforms was studied in 38 endocrine pancreatic tumours and gut neuroendocrine tumours using antibodies directed against products of exons v3, v4-v5, v6, v7-v8 as well as against the standard CD44 molecule (CD44H). CD44 gene expression was also analysed by reverse transcription PCR (RT-PCR) in nine endocrine and seven carcinoid tumours.Results-All gastrinomas except one (nine of 10) and about half of the other endocrine pancreatic tumours (seven of 15) expressed CD44v6. Most (10/11) midgut carcinoid tumours were CD44v6 negative, with no detectable immunostaining. CD44v3, CD44v4-v5 and CD44v7-v8 were not expressed in any of these tumours. CD44 mRNA analysis illustrated a complex splice pattern and expression of large CD44 isoforms in CD44v6 positive endocrine tumours, whereas the standard form only was detected in midgut carcinoid tumours. No correlation between CD44 variant expression and tumour metastasis was observed.Conclusions-CD44 variants encoding exon v6 are preferentially expressed both in gastrinomas and in most pancreatic endocrine tumours. In contrast to other tumours, the expression of CD44v6 in pancreatic neuroendocrine tumours does not seem to be correlated with tumour dissemination.</p>","PeriodicalId":87395,"journal":{"name":"Clinical molecular pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.49.4.m203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26016850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of human papillomavirus in vulval carcinoma using semi-nested PCR and restriction enzyme typing: a rapid and sensitive technique.","authors":"N H Cartwright,&nbsp;L J Cassia,&nbsp;A J Easton,&nbsp;A G Morris","doi":"10.1136/mp.49.4.m236","DOIUrl":"https://doi.org/10.1136/mp.49.4.m236","url":null,"abstract":"<p><p>Aims-To develop a highly sensitive technique for the reliable detection and typing of human papillomavirus (HPV) DNA in clinical tissue.Methods-A two step, semi-nested PCR was used with primers spanning the L1 region of the HPV genome and capable of detecting HPV DNA of all known HPV types. The clinical samples were typed by digestion of the 412 base pair PCR product with Rsa I, generating unique fragments for each HPV type. Thirteen samples were screened by this method, including nine vulval carcinoma samples and four wart samples from the penis and vulva.Results-Experiments using DNA extracted from HPV DNA positive cell lines-that is, CaSki (HPV type 16) and HeLa (HPV type 18) established that the technique could detect as few as 50 HPV copies and that the predicted Rsa I fragments from HPV types 16 and 18 were generated. The predicted 412 base pair fragment was observed for all 13 clinical samples subjected to semi-nested PCR. Rsa I digestion of the product of the second round of PCR permitted the positive identification of the HPV type in most cases.Conclusions-This technique provides an effective and rapid means of detecting HPV DNA, in most cases providing the HPV type. High risk HPV types were always detected in the nine vulval carcinoma samples analysed. The amount of tissue available from the biopsy specimens was small, confirming the sensitivity of the method.</p>","PeriodicalId":87395,"journal":{"name":"Clinical molecular pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.49.4.m236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26016857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphotropic herpes virus (EBV, HHV-6, HHV-8) DNA sequences in HIV negative Castleman's disease.","authors":"P Barozzi,&nbsp;M Luppi,&nbsp;L Masini,&nbsp;R Marasca,&nbsp;M Savarino,&nbsp;M Morselli,&nbsp;M G Ferrari,&nbsp;M Bevini,&nbsp;G Bonacorsi,&nbsp;G Torelli","doi":"10.1136/mp.49.4.m232","DOIUrl":"https://doi.org/10.1136/mp.49.4.m232","url":null,"abstract":"<p><p>Aim-To evaluate the possible involvement of lymphotropic herpes viruses in Castleman's disease.Methods-Archival formalin fixed, paraffin wax embedded biopsy specimens from 16 HIV negative patients (11 with localised and five of multicentric disease) were studied. Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6) and human herpes virus-8 (HHV-8) DNA was detected using PCR. PCR was also used to characterise the EBV genomes and the clonal status of the lesions.Results-EBV sequences were identified in nine (56%) cases. The main EBV genotype detected was type 1. Two (12%) cases were positive for both HHV-6 and EBV sequences. HHV-8 sequences were detected in one case of localised Castleman's disease, the sequence of which differed from that of the HHV-8 prototype. No clonal immunoglobulin gene rearrangements were found.Conclusions-EBV DNA was detected in a substantial proportion of cases, suggesting that it may have a role in the pathogenesis of Castleman's disease, unlike HHV-6 which was detected rarely. This is the first report of HHV-8 specific sequences in the localised from of the disease.</p>","PeriodicalId":87395,"journal":{"name":"Clinical molecular pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.49.4.m232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26016856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"c-erbB3 protein expression in ovarian cancer.","authors":"T Rajkumar,&nbsp;G W Stamp,&nbsp;C M Hughes,&nbsp;W J Gullick","doi":"10.1136/mp.49.4.m199","DOIUrl":"https://doi.org/10.1136/mp.49.4.m199","url":null,"abstract":"<p><p>Aims-To study the prevalence of overexpression of c-erbB3 growth factor receptor in ovarian carcinomas and to analyse its relation to histological subtype, stage and grade of the tumours.Methods-Ninety eight ovarian carcinomas were evaluated immunohistochemically using the RTJ1 monoclonal antibody raised against a synthetic peptide, the sequence of which was derived from the cytoplasmic domain of the c-erbB3 protein.Results-Of the tumours, 16% (16/98) overexpressed c-erbB3 protein relative to normal ovarian epithelium, whereas 22% (22/98) were completely negative. There was a statistically significant association between overexpression and well differentiated grade.Conclusions-These findings suggest that c-erbB3 protein overexpression occurs in a significant proportion of ovarian cancers and is correlated with differentiation. Overexpression may merit further investigation as a potential prognostic indicator and as a target for new treatment.</p>","PeriodicalId":87395,"journal":{"name":"Clinical molecular pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.49.4.m199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26018535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interphase ribosomal RNA cistron staining in thyroid epithelial cells in Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland.","authors":"N N Mamaev,&nbsp;E N Grynyeva,&nbsp;Y V Blagosklonnaya","doi":"10.1136/mp.49.4.m240","DOIUrl":"https://doi.org/10.1136/mp.49.4.m240","url":null,"abstract":"<p><p>Aim-To evaluate the expression of ribosomal cistrons in human thyroid epithelial cells (TECs) of patients with Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland.Methods-TEC nucleoli were investigated in fine needle biopsy specimens from 10 controls, 39 patients with Grave's disease, 15 with Hashimoto's thyroiditis, 56 with benign, and 15 with malignant tumours of the thyroid. A one step silver staining method was applied. In most cases serum concentrations of thyroxine and triiodothyronine as well as goitre size were determined. In every case 100 TECs were evaluated for the mean numbers of nucleoli and for the average number of argyrophilic nucleolar organiser regions (AgNORs) per nucleus.Results-NORs were activated in all patients, but not in controls. The numbers of AgNORs in patients with Grave's disease were closely correlated with thyroxine or triiodothyronine, or both, concentrations and with the size of the thyroid. In patients with Hashimoto's thyroiditis about 30% of TECs nucleoli did not contain AgNORs, whereas others were heavily impregnated with silver. Compared with controls and benign tumours, the nucleoli of carcinomatous TECs were larger and irregular in shape. The mean number of AgNORs per nucleus in malignant cells was higher than that in their benign counterparts.Conclusions-The mechanism by which NORs are activated in TECs varies depending on the type of lesion. The higher AgNOR score in TECs from malignant tumours can be used to distinguish them from their benign counterparts.</p>","PeriodicalId":87395,"journal":{"name":"Clinical molecular pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.49.4.m240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26022021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Karyotypic and molecular abnormalities in chronic lymphocytic leukaemia.","authors":"C D Fegan,&nbsp;F E Davies","doi":"10.1136/mp.49.4.m185","DOIUrl":"https://doi.org/10.1136/mp.49.4.m185","url":null,"abstract":"","PeriodicalId":87395,"journal":{"name":"Clinical molecular pathology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.49.4.m185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26018534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}