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Biomedical subjects

S Dirnhofer

Publications and source records attributed to S Dirnhofer.

At least 19 recordsLinked to original sources
PubMed2006

Human chorionic gonadotropin (hCG) in the male reproductive tract.

Normal hypothalamic-pituitary testicular and prostatic functions are essential for maintenance of male fertility, whereby glycoprotein hormones (GPH) as well as androgens are major endocrine and local regulators. We have investigated whether the GPH human chorionic gonadotropin (hCG) and the free alpha and beta subunits thereof are produced in the target organs themselves and potentially act as auto/paracrine modulators of fertility. Immunofluorometric assays (IFMAs) based on our panel of highly selective monoclonal antibodies, immunohistochemistry (IHC), confocal laser scanning microscopy (CLSM) and 1- and 2D gel electrophoreses with subsequent western blotting have been utilized for the detection of hCGalpha, hCGbeta and its metabolite hCGbeta core fragment (cf) in human testis, prostate and seminal plasma. Both organs synthesize hCGalpha and hCGbeta, which are subsequently detectable at high concentrations in seminal plasma of healthy probands (n=17): hCGalpha 2630+/-520 ng/mL (mean+/-S.E.M.), hCGbeta 2+/-0.28 ng/mL, hCGbetacf and hCG 0.19+/-0.039 ng/mL. These parameters significantly exceed physiological values, e.g. ten thousand-fold in the case of hCGalpha, in serum of young men (n=20): hCGalpha 0.142+/-0.054 ng/mL (mean+/-S.E.M.), hCGbeta 0.05 ng/mL and hCG 0.004+/-0.003 ng/mL. Levels of these markers were not correlated with sperm counts. Of all body fluids including those of pregnant women seminal plasma is the richest physiological source for genuine free i.e. non-dissociated GPHalpha (M(r,app) 23k) which may even appear as di- or tetramers. Its concentration is similar to that observed in maternal serum (weeks 10-12 of gestation) and in extra-embryonic coelomic fluid. In contrast to those fluids where ratios of free subunits to hCG are in the range of 1:100 highly inverse ratios in the range of 10.000:1.000:1 were observed for hCGalpha:hCGbeta:hCG in seminal plasma. hCGalpha is not derived from heterodimeric GPH suggesting hCG-independent functions of hCGalpha and hCGbeta in male and female fertility.

Blotting, Western↗
PubMed2006

Epidemiology of non-Hodgkin lymphomas in Tyrol/Austria from 1991 to 2000.

AIMS: To analyse the entity specific incidence and disease specific survival (DSS) of non-Hodgkin lymphomas (NHLs) in Tyrol/Austria, 1991-2000. METHODS: Data from 1307 NHLs (excluding primary cutaneous lymphomas and monoclonal gammopathies of undetermined significance) were obtained. Current status was available for all patients. Except for 29 cases of small lymphocytic (CLL/SLL), lymphoblastic leukaemia (ALL), and myeloma (MM), which were diagnosed cytologically, diagnoses were reclassified on paraffin wax embedded archival material according to new World Health Organisation criteria. Sex specific age adjusted standardised incidence rates were computed using Segi's population weighting. Annual incidence changes were calculated by weighted least square regression analysis. Survival was estimated by the Kaplan-Meier method and compared by log rank test. RESULTS: NHL more frequently affected men (male/female ratio, 1.52). Mean age of occurrence was 61 and 66 years for men and women, respectively. The incidence rate of 14.3 remained constant. There was a significant increase in diffuse large B cell lymphoma (DLBCL) and decrease in CLL/SLL in men, and a decrease in MM in women. Overall DSS was 64% during the mean follow up (43 months). Age, T-NHL, lambda light chain restriction in MM, and male sex in CLL/SLL were associated with poor prognosis. In B-NHL, DSS decreased in the following order: hairy cell leukaemia, marginal zone lymphoma, follicular lymphoma, Burkitt lymphoma, ALL, DLBCL, CLL, MM, and mantle cell lymphoma. CONCLUSIONS: The incidence of NHL in Tyrol has changed in the past decade, with a significant increase in DLBCL, decrease in CLL/SLL in men, and decrease in MM in women.

Adolescent↗
PubMed2006

High predictive value of epidermal growth factor receptor phosphorylation but not of EGFRvIII mutation in resected stage I non-small cell lung cancer (NSCLC).

AIMS: Overexpression and mutation of epidermal growth factor regulator (EGFR) are frequently found in the carcinogenesis of non-small cell lung cancer (NSCLC). Because targeting of this receptor has proven therapeutic efficacy, studying EGFR has become a matter of particular scientific interest. The present study analysed the EGFR receptor, rate of EGFRvIII mutations, and rate of activated phosphorylated EGFR (pEGFR) by immunohistochemistry on cryostat sections. METHODS: Surgically obtained tumour specimens of a series of 78 NSCLC patients and 66 adjacent tumour free specimens were examined immunohistochemically using monoclonal antibodies to stain EGFR, pEGFR, and EGFRvIII. RESULTS: EGFRvIII and pEGFR expression was found in 42% and 26% of the tumours respectively and both were increased significantly compared with tumour free samples. EGFR, pEGFR, and EGFRvIII expression did not correlate with any of the previously tested markers (c-erbB-2, c-erbB-3, p53, ki-67, and microvessel density). Similar distributions of immunohistochemical profiles were seen, regardless of histological subtype, age, or sex. In stage I patients, EGFR phosphorylation at tyrosine residue 845 proved to be an independent prognostic factor. CONCLUSION: Because pEGFR correlated with poor prognosis, it can be speculated that it plays a crucial biological role in the pathogenesis of NSCLC.

Biomarkers, Tumor↗
PubMed2006

Plasma cell quantification in bone marrow by computer-assisted image analysis.

BACKGROUND: Minor and major criteria for the diagnosis of multiple meloma according to the definition of the WHO classification include different categories of the bone marrow plasma cell count: a shift from the 10-30% group to the > 30% group equals a shift from a minor to a major criterium, while the < 10% group does not contribute to the diagnosis. Plasma cell fraction in the bone marrow is therefore critical for the classification and optimal clinical management of patients with plasma cell dyscrasias. The aim of this study was (i) to establish a digital image analysis system able to quantify bone marrow plasma cells and (ii) to evaluate two quantification techniques in bone marrow trephines i.e. computer-assisted digital image analysis and conventional light-microscopic evaluation. The results were compared regarding inter-observer variation of the obtained results. MATERIAL AND METHODS: Eighty-seven patients, 28 with multiple myeloma, 29 with monoclonal gammopathy of undetermined significance, and 30 with reactive plasmocytosis were included in the study. Plasma cells in H&E- and CD138-stained slides were quantified by two investigators using light-microscopic estimation and computer-assisted digital analysis. The sets of results were correlated with rank correlation coefficients. Patients were categorized according to WHO criteria addressing the plasma cell content of the bone marrow (group 1: 0-10%, group 2: 11-30%, group 3: > 30%), and the results compared by kappa statistics. RESULTS: The degree of agreement in CD138-stained slides was higher for results obtained using the computer-assisted image analysis system compared to light microscopic evaluation (corr.coeff. = 0.782), as was seen in the intra- (corr.coeff. = 0.960) and inter-individual results correlations (corr.coeff. = 0.899). Inter-observer agreement for categorized results (SM/PW: kappa 0.833) was in a high range. CONCLUSIONS: Computer-assisted image analysis demonstrated a higher reproducibility of bone marrow plasma cell quantification. This might be of critical importance for diagnosis, clinical management and prognostics when plasma cell numbers are low, which makes exact quantifications difficult.

Algorithms↗
PubMed2005

A case of post-transplant lymphoproliferative disease presenting as CD20-expressing, Epstein-Barr-virus positive Hodgkin lymphoma.

Classical Hodgkin lymphoma (HL) is a rare complication after solid organ transplantation. We describe the first case of a patient developing CD20-positive HL after renal transplantation treated with the monoclonal antibody rituximab. Treatment with single agent rituximab led to partial remission. Subsequent combined modality treatment consisting of chemotherapy (adriamycin, bleomycin, vindesin and dacarbacin), immunotherapy (rituximab) and involved field irradiation achieved complete remission. Different therapeutic strategies in the treatment of patients developing lymphoproliferative disease - and particularly HL - after solid organ transplantation are discussed.

Adult↗
PubMed2004

[Expression profile and prognostic significance of CD24, p53 and p21 in lymphomas. A tissue microarray study of over 600 non-Hodgkin lymphomas].

BACKGROUND AND OBJECTIVE: Tissue microarrays allow the simultanous, rapid and standardized in-situ analysis of up to 1000 different tissue samples on a single glass slide. We investigated the expression profil and the prognostic significance of CD24, p53 and p21 using a Non-Hodgkin-Lymphoma tissue microarray. METHODS: Over 600 well documented Non-Hodgkin-Lymphomas, consisting of 341 diffuse large B-cell lymphomas, 86 follicular lymphomas, 81 chronic lymphatic leukemias/small lymphocytic lymphomas, 51 primary mediastinal diffuse large B-cell lymphomas, 26 mantle cell lymphomas, 8 lymphoplasmocytic lymphomas, 8 T-cell-lymphomas NOS und 2 Burkitt lymphomas were brought into array format. The expression of CD24, p53 and p21 was analysed semiquantitatively by immunohistochemistry. The immunophenotype p53+/p21- (Deltap53) was used as a surrogat for p53 gene mutations. The expression profile was compared to clinical data and the overall survival in the subgroup of diffuse large B-cell lymphomas. RESULTS: 91% of the analyzed Non-Hodgkin-lymphomas (473 of 522 cases) showed CD24 positivity. CD24 Expression was not associated with survival. Deltap53 was found in thirteen percent of all lymphomas (70 of 539 cases), the subgroup of the diffuse large B-cell lymphomas demonstrated the highest Deltap53 (21%). In a multivariate cox regression analysis, a high international prognostic index and Deltap53 were independent markers of bad survival. CONCLUSION: The TMA-technology allows also in lymphoma research the simultanous, cost-effective and standardized analysis of large patient cohorts. Deltap53 revealed as an independent negative prognostic factor in diffuse large B-cell lymphomas. It can easily be determined in daily routine practice.

Adolescent↗
PubMed2004

Biomarkers in non-small cell lung cancer prevention.

Identification of biomarkers is one of the most promising approaches for the detection of early malignant or even premalignant lesions with the chance of diagnosing early stages of non-small cell lung cancer that could be treated curatively. Alterations of chromosomes (3p, 5q, 9p), genes (Rb, C-myc, C-mos, hTERT), proteins (p16, p53, K-ras, hnRNP A2/B1, MCM2, EGFR, erbB-2, erbB-3, erbB-4) and others can be found in lung cancer. Some of these occur at early stages of the disease and few could serve as potential screening markers. The actual literature is reviewed and the relevance of the different biomarkers for early lung cancer detection is discussed.

Biomarkers, Tumor↗
PubMed2004

Rare expression of KIT (CD117) in lymphomas: a tissue microarray study of 1166 cases.

AIMS: Imatinib mesylate specifically inhibits KIT tyrosine kinase activity, and has been proven to be effective in the treatment of gastrointestinal stromal tumours. Because other KIT-expressing malignancies might benefit from Imatinib therapy, we evaluated the distribution and expression of KIT in 1166 cases of malignant lymphoma. MATERIALS AND RESULTS: Tissue microarrays (TMAs) containing 824 non-Hodgkin's lymphoma (NHL) and 342 Hodgkin's lymphoma (HL) cases were immunohistochemically analysed for the expression of the KIT protein. Two KIT-positive NHLs were sequenced using polymerase chain reaction analysis. One T-cell lymphoma and one follicular lymphoma of the 747 NHL cases (0.3%) were positive for KIT. All HLs were Kit-negative. None of the KIT-positive cases showed a kit gene mutation. CONCLUSIONS: KIT expression is a very rare event in NHL and virtually absent in HL. In the few positive cases, the aberrant expression is not caused by a mutation in the 'hot-spots' of the kit gene, indicating that treatment of these tumours with Imatinib may be ineffective.

Adolescent↗
PubMed2004

Unfavourable prognosis of patients with trisomy 18q21 detected by fluorescence in situ hybridisation in t(11;18) negative, surgically resected, gastrointestinal B cell lymphomas.

BACKGROUND: The most frequent cytogenetic alteration in gastrointestinal (GI) B cell lymphoma (BCL) is t(11;18)(q21;q21). GI B cell non-Hodgkin lymphomas lacking this translocation vary in their biology and clinical outcome. The t(11;18) negative subgroup shows increased numerical changes of chromosome 18, although its clinical relevance remains unknown. METHODS: Thirty surgically resected primary GI BCLs were examined-11 low grade marginal zone mucosa associated lymphoid tissue (MALT) lymphomas, four marginal zone lymphomas with diffuse large BCL (DLBCL), and 15 de novo DLBCLs. Chromosome 18 aberrations were examined using interphase fluorescence in situ hybridisation. Trisomy 18 was studied applying a centromere 18 probe and a dual colour probe for the MALT1 gene at 18q21. RESULTS: Using the MALT1 probe, only one marginal zone MALT lymphoma had a break apart pattern, indicating t(11;18) or variants. In the GI BCLs lacking MALT1 breaks, trisomy 18q21 was seen in seven patients (four with complete trisomy 18 and three with partial trisomy of 18q21). Trisomy 18q21 was found in two of 10 low grade MALT lymphomas and five of 19 GI BCLs with large cell component. Six of 17 patients with trisomy 18q21 presented with >/= stage II and one of 12 with stage I disease. Trisomy 18q21 was associated with significantly shorter disease specific survival in the whole group and GI BCLs with large cell component, but not in the low grade group. CONCLUSIONS: Trisomy 18q21, including MALT1, may be associated with advanced tumour stage and may be a predictor of poor outcome in surgically resected primary GI BCLs.

Adult↗
PubMed2004

CD133 positive endothelial progenitor cells contribute to the tumour vasculature in non-small cell lung cancer.

AIMS: Recent results generated in a mouse model suggest that tumour angiogenesis/vasculogenesis can be initiated and maintained by bone marrow derived endothelial progenitor cells. This present study investigated the distribution and frequency of CD133 positive endothelial progenitor cells in patients with non-small cell lung cancer (NSCLC) (tumour tissue and tumour free lung regions) and healthy controls using fresh frozen specimens. The novel marker CD133 identifies human haemopoetic precursor cells, in addition to human endothelial progenitor cells. METHODS: Seventy nine lung cancer specimens and 66 adjacent histologically tumour free tissues of the same patient cohort were analysed; 11 postmortem specimens from control patients who did not suffer from malignant disease served as controls. Cryostat sections were stained for CD133, CD31, vascular endothelial growth factor receptor 2 (VEGFR-2; KDR), p53, and the proliferation marker Ki-67, and the correlations were analysed. RESULTS: Forty three of 63 evaluable tumour specimens had increased numbers of CD133 positive cells and in some cases capillary forming CD133 positive structures were detectable. In addition, 30 of 63 specimens had raised expression of KDR and 29 of 63 had increased MVD. Increased CD133 expression marginally correlated with raised KDR expression but not with p53 and Ki-67. CONCLUSION: A significant increase in CD133 positive cells was documented in patients with NSCLC, suggesting an involvement of endothelial progenitor cells in tumour vasculogenesis and tumour growth in these patients.

AC133 Antigen↗
PubMed2004

Cutaneous plasmablastic lymphoma in an HIV-positive male: an unrecognized cutaneous manifestation.

Plasmablastic lymphoma (PBL) is a rare and relatively new entity originally described in HIV-infected individuals. This subset of Epstein-Barr-virus (EBV)-related non-Hodgkin lymphomas is now regarded as a distinct clinicopathological category of AIDS-associated lymphomas occurring preferentially in the oral cavity and showing a poor prognosis. We describe for the first time an EBV-associated PBL with an isolated cutaneous distribution on the lower extremities in an HIV-infected heterosexual male and point to the unique clinical, morphological and immunophenotypic characteristics of this lymphoma. The patient presented with fast growing solid and livid nodules on both legs. The large, blastic tumor cells showed the following immunophenotype: CD138+, CD45+, CD20-, CD10-, CD3-, CD30-, bcl-2-, bcl-6-, LMP-1- and EMA-. The proliferation fraction (Mib-1) was >90%. EBV association was demonstrated by in situ hybridization (EBV-encoded RNAs 1/2). Polymerase-chain-reaction-based DNA analysis demonstrated a clonal IgH rearrangement in the absence of a bcl-2/IgH translocation. PBL in HIV patients may occur not only in the oral cavity, but can probably involve any other organs including the skin.

Adult↗
PubMed2003

Rare KIT (CD117) expression in multiple myeloma abrogates the usefulness of imatinib mesylate treatment.

BACKGROUND: Imatinib mesylate blocks the tyrosine kinase activity of KIT (CD117) and is an effective treatment for gastrointestinal stromal tumors. In multiple myeloma, KIT expression has been detected by flow cytometry in about 33% of specimens, but no previous immunohistochemical assessment has yet been made of the expression pattern of KIT. MATERIALS AND METHODS: We performed immunohistochemical analyses of 100 patients, including 72 with multiple myeloma (MM), 8 with lymphoplasmacytic lymphoma (LPL), 10 with monoclonal gammopathy of undetermined significance (MGUS) and 10 with reactive plasmocytosis. One KIT-positive MM was sequenced using polymerase chain reaction analysis. RESULTS: In MM, only 2 cases (2.8%) were KIT positive. The great majority of the cases (97, 2%) did not express the KIT receptor tyrosine kinase. No mutation of the c-kit gene was detected. CONCLUSIONS: KIT expression is a rare event in MM and not detectable in MGUS and LPL. Therefore, treatment with imatinib is unlikely to be effective in these patients.

Adult↗
PubMed2003

Cytokine-regulated expression of collagenase-2 (MMP-8) is involved in the progression of ovarian cancer.

Matrix metalloproteinases (MMPs) have been implicated in ovarian cancer progression. Among them, MMP-8 that degrades type I collagen may play a crucial role. The aim of our study was to determine MMP-8 expression and regulation in ovarian cancer and its association with other MMPs and tissue inhibitors of metalloproteinases (TIMPs). Tissue microarrays (TMAs) containing tissue cylinders from 302 patients were used for immunohistochemical studies. In addition, MMP-8 expression in vitro was analysed by a specific immunoassay and PCR-analysis. MMP-7 (81%), MMP-8 (95%), MT3-MMP (100%), TIMP-2 (100%), and TIMP-3 (96%) were expressed in all the OVCAs, but the staining intensities varied. MMP-3 (6%), MMP-9 (57%) and TIMP-1 (43%) expressions were more rarely detected. Only MMP-8 expression levels correlated with tumour grade (P<0.01), tumour stage (P<0.01), and a poor prognosis (P<0.05). MMP-8 protein and gene expression in vitro was found to be significantly upregulated by interleukin-1beta (IL-1beta, P<0.01). The data indicate that MMP-8 overexpression in OVCAs is regulated by IL-1beta and that pro-inflammatory cytokines may promote the invasive potential of ovarian cancer.

Adult↗
PubMed2003

Heparanase-1 gene expression in normal, hyperplastic and neoplastic prostatic tissue.

Heparanase-1 (Hpa-1) has been implicated in tumour invasion and metastasis. In the present study, we evaluated the clinicopathological significance of Hpa-1 mRNA expression in prostate cancer and non-cancerous prostatic tissue by one-step polymerase chain reaction (PCR) of laser microdissected prostatic gland cells. In addition, cell type-specific expression of Hpa-1 mRNA in prostatic tissue was analysed by in situ hybridisation. Hpa-1 mRNA expression was found in 50% of normal and 40% of hyperplastic prostatic tissue. In situ hybridisation showed that Hpa-1 mRNA was strongly expressed in prostate gland cells. Of the 26 prostate carcinomas tested, 42% were positive for Hpa-1 mRNA. However, in non-cancerous prostatic tissue, Hpa-1 mRNA was significantly more often expressed than in less differentiated or more invasive prostate cancers (P<0.05). In situ hybridisation revealed only focal Hpa-1 mRNA expression in the neoplastic gland cells. Hpa-1 mRNA expression in the tumours significantly correlated with tumour differentiation and tumour stage (P<0.05). Our data indicate that Hpa-1 gene expression may be lost during dedifferentiation of prostatic gland cells.

Adult↗
PubMed2003

The expression pattern of CD56 (N-CAM) in human bone marrow biopsies infiltrated by acute leukemia.

In hematological neoplasms CD56 (N-CAM) is expressed by T/natural killer (NK) cell lymphoma, by most neoplastic plasma cells in multiple myeloma and also in a subset of acute myelogenous leukemias (AML). In the latter, it is an indicator of poor clinical outcome. Most of the data on CD56 expression in acute leukemia have been obtained by flow cytometric analysis. Up to now, no systematic analysis of the expression pattern of CD56 in formalin fixed paraffin embedded bone marrow biopsies of acute leukemias has been performed. We immunohistochemically studied the expression of CD56 in a series of 141 bone marrow biopsies fixed in Sublimat Mercury II Chloride (SUSA) including 100 cases of AML FAB M0-M7, 11 cases of AML not further specified, 3 cases of biphenotypical leukemia, 20 cases of acute lymphoblastic leukemia (ALL) and 7 cases of reactive bone marrow biopsies. Overall, 14 of 134 (10%) leukemia cases were positive for CD56. Detail analysis revealed positivity in 5/13 cases of AML M5 (38%), 3/9 AML M1 (33%), 1/8 AML M0 (13%), 1/11 AML not specified (9%), 2/31 AML M2 (7%) and 2/26 AML M4 (8%). All cases of ALL and biphenotypic leukemias were CD56 negative. The CD56 expression in AML M5 was statistically significant (p = 0.003). On paraffin embedded bone marrow biopsies CD56 expression occurs in de novo AML with an overall frequency of 13%. It is significantly correlated with AML M5, which is positive in 38% of the cases. Cases of ALL are consistently CD56 negative.

Adult↗