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U Löhrs

Publications and source records attributed to U Löhrs.

At least 19 recordsLinked to original sources
PubMed2001

Her-2/neu analysis in archival tissue samples of human breast cancer: comparison of immunohistochemistry and fluorescence in situ hybridization.

PURPOSE: The objective of our study was to compare the methods used in the literature to analyze HER-2/neu status on archival breast cancer tissue. Therefore, a series of antibodies was evaluated to assess their immunohistochemical (IHC) sensitivity in correlation to gene amplification determined by fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: HER-2/neu overexpression was studied on paraffin sections of 85 invasive breast cancers using a panel of five monoclonal (9G6, 3B5, CB11, TAB250, GSF-HER2) and two polyclonal antibodies (A8010, A0485) in addition to the HercepTest (DAKO, Glostrup, Denmark). HER-2/neu gene amplification was determined by FISH using a dual-color probe (PathVysion; Vysis, Stuttgart-Fasanenhof, Germany). RESULTS: HER-2/neu overexpression was demonstrated in 26% (9G6, TAB250, GSF-HER2), 27% (3B5, CB11), 33% (A8010) and 42% (A0485, HercepTest) of the tumors. FISH on paraffin sections identified gene amplification in 28% of the tumors. Strongly positive IHC results (3+) were always associated with gene amplification. Among the 16 tumors presented with weakly positive IHC results (2+) using the HercepTest, 12 (75%) lacked gene amplification. CONCLUSION: The comparison of IHC and FISH demonstrated an excellent correlation of high-level HER-2/neu overexpression (3+) with gene amplification; ie, FISH does not provide further information in these tumors. However, weakly positive IHC results (2+) obtained with the HercepTest share only a minor association with gene amplification.

Antibodies, Monoclonal↗
PubMed2001

Altered distribution of beta-catenin, and its binding proteins E-cadherin and APC, in ulcerative colitis-related colorectal cancers.

The beta-catenin pathway plays a central role in transcriptional signaling and cell-cell interactions in colonic epithelium. Alterations of the expression of beta-catenin, and its binding partners E-cadherin and the adenomatous polyposis coli protein (APC), are frequent events in sporadic colorectal cancer. Ulcerative colitis (UC)-related cancers originate in a field of chronic inflammation and therefore may have different alterations in the beta-catenin pathway than sporadic cancers. To test this hypothesis, expression and subcellular localization of beta-catenin, E-cadherin, and APC were detected by immunohistochemistry in paraffin sections from 33 UC-related and 42 sporadic colorectal cancers. Although beta-catenin and E-cadherin expression were predominantly limited to the lateral cell membrane in normal colonic epithelium, both tumor groups showed an overall shift from membranous to cytoplasmic expression for these proteins. An increase in nuclear localization of beta-catenin and a decrease in cytoplasmic APC expression also were seen in both cancer groups compared with normal epithelium. Abnormal beta-catenin expression was more closely linked to E-cadherin alterations in UC-related cancers than in sporadic cancers. In contrast, abnormal beta-catenin expression was more closely linked to APC alterations in sporadic cancers than in UC-related cancers. These data suggest that alterations of the beta-catenin pathway are important in both UC-related and sporadic colorectal cancers. However, differences in the expression patterns of beta-catenin, E-cadherin, and APC between UC-related and sporadic colorectal cancers suggest that the specific alterations in this pathway may differ in these two cancer groups.

Adenomatous Polyposis Coli Protein↗
PubMed2001

Cellular chimerism of the lung after transplantation. An interphase cytogenetic study.

The present study evaluated the origin of endothelial and epithelial cells, as well as of lymphocytes and macrophages, after lung transplantation. Biopsy specimens from patients who underwent lung and heart-lung transplantation and received organs of sex-mismatched donors were studied by means of nonisotopic in situ hybridization with DNA probes of the X and Y chromosome. By means of monoclonal antibodies against leukocytes, T and B lymphocytes, and macrophages, the various infiltrating cell types were analyzed. In all allografted lungs, the endothelial cells and bronchial and alveolar epithelium retained the donor sex type. The lymphocytes of the donor were almost completely replaced by recipient cells 1 month after transplantation. Low numbers of alveolar macrophages of the donor were present during the entire period under study. Low numbers of donor lymphocytes and high numbers of donor alveolar macrophages in the allografted lung seem to be correlated with a worse clinical course.

Antibodies, Monoclonal↗
PubMed2000

20q13 and cyclin D1 in ovarian carcinomas. Analysis by fluorescence in situ hybridization.

In ovarian carcinomas, alterations of the chromosomal region 20q13 and the cyclin D1 gene have been described. This study has sought to determine their prognostic significance. Fluorescence in situ hybridization (FISH) on dissociated nuclei and paraffin sections with DNA probes for 20q13.2 and cyclin D1, as well as immunohistochemistry (cyclin D1), were applied to formalin-fixed tissue of 69 invasive ovarian carcinomas, mainly of serous type. On dissociated nuclei 33/47 cases (70%) and on tissue sections 13/66 cases (20%) demonstrated an increase of 20q13.2 copies. The presence of > or =4 copies per nucleus (isolated nuclei) and > or =3 copies per nucleus (sections) was associated with an adverse prognosis (Kaplan-Meier for FIGO stage III after stratification for residual tumour: p=0.0049 and p=0.03, respectively). Thirty-four out of 47 cases (72%) showed an increase of cyclin D1 copies. Kaplan-Meier analysis for FIGO stage III after stratification for residual tumour>2 cm or < or =2 cm revealed an unfavourable outcome for cases with more than two cyclin D1 copies (p=0.04). No correlation was seen between FISH and immunohistochemistry. Multivariate analysis identified residual tumour (p=0.0002), 20q13.2 gain (p=0.0004) and cyclin D1 gain (p=0.0343) as independent prognostic factors. It is concluded that gains of chromosomal region 20q13.2 and the cyclin D1 gene are frequent and biologically important events, with prognostic relevance, in advanced ovarian carcinomas.

Adult↗
PubMed2000

Prognostic significance of apoptosis and associated factors in oral squamous cell carcinoma.

Tumour progression is characterised by an imbalance between cell proliferation and apoptosis. The aim of our study was to estimate the importance of proliferation and apoptosis associated parameters in primary squamous cell carcinomas (SCCs) of the oral cavity and oropharynx. For determination of apoptosis, the enzymatic labelling of DNA fragmentation with a terminal transferase reaction was used in 156 tissue samples of 107 patients, including corresponding lymph-node metastases in nine cases. P53, bcl-2, and Ki-67 were determined immunohistologically. P53 was detectable in 50.5% of the cases. Positive staining was associated significantly with decreased apoptosis (P<0.003). Bcl-2 was upregulated in 31.8% of the cases depending on the tumour grading (P<0.001) and correlated negatively with apoptosis (P<0.001). Proliferation (P<0.006) and apoptosis (P<0.03) were enhanced in larger tumours, though a direct correlation between these two parameters was not proven. Nevertheless, in contrast to the conventional tumour staging and grading, neither the expression of p53 or bcl-2 nor the apoptosis or Ki-67 measurements were able to predict survival or recurrence-free survival of the patients suffering from a SCC in the oral cavity or oropharynx. Our observations suggest that the function of wild-type p53 to induce apoptosis is lost in at least half of the SCCs under study and that the physiological function of bcl-2 as potent inhibitor of apoptosis is widely preserved in oral SCC.

Adult↗
PubMed2000

[Differential diagnosis of lymphoepithelial lesions of salivary glands. With particular reference to characteristic duct lesions].

Several salivary gland diseases present with the histomorphological features of a lymphoepithelial lesion with or without cyst formation. Some of the most important differential diagnoses (Sjögren's syndrome, marginal zone B-cell lymphoma, HIV-associated cystic lymphoepithelial lesion) are systemic diseases and require further investigation and therapy. However, in small biopsy specimens and in cases without relevant clinical information an exact diagnosis may be difficult to obtain. We have recently determined that the characteristic lymphoepithelial duct lesions develop by proliferation of basal cells of striated ducts, while we could not confirm the previously postulated participation of myoepithelial cells ("epimyoepithelial lesion/sialadenitis"). Although these duct lesions are typical of Sjögren's syndrome, they manifest in several diseases of salivary glands, exhibiting characteristic patterns concerning frequency and localization. This review discusses the most important lymphoepithelial diseases of salivary glands with respect to clinical presentation and histomorphology. Particular emphasis is placed on the lymphoepithelial duct lesions.

Diagnosis, Differential↗
PubMed2000

[Melanoma inhibitory activity (MIA). Evaluation of a new tumor-associated antigen as a serum marker for uveal melanomas].

BACKGROUND: Currently no serological marker for the monitoring of uveal melanoma and its metastases is available. The novel tumor associated antigen Melanoma inhibitory activity (MIA) is expressed in the uveal melanoma and it's metastatic lesions. METHOD: We report about the serum samples of 38 patients with uveal melanomas. 4 of these patients had overt metastatic disease. A nonradioactive one step ELISA was used to quantify the MIA serum levels. RESULTS: In the 34 patients without overt metastatic disease the serum concentration of MIA was mean (+/- 1 SD) 3.6 +/- 1.0 ng/ml. In the 4 patients with overt metastatic disease the serum concentration of MIA was mean (+/- 1 SD) 27.7 +/- 3.0 ng/ml. The difference was statistically highly significant (student t test: p = 0.0001). CONCLUSION: MIA is expressed in primary and metastatic lesions of uveal melanomas. The elevation of MIA serum levels in patients with metastatic disease from melanomas suggests a promising role as a serum marker for monitoring patients with uveal melanoma.

Aged↗
PubMed2000

Impairment of genomic DNA binding to a putative dysfunctional receptor on erythrocytes independent of complement and antibodies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by a variety of autoantibodies and other immune abnormalities indicative of an immunological hyperactivity. Antibodies against native DNA, however, are a disease-specific marker and play a major role in the pathogenesis of systemic or organ-specific disease manifestations. Nevertheless, the mechanisms causing the appearance of autoantibodies and immune complexes in SLE are not yet understood. Here, we report that chromosomal DNA and other forms of nucleic acids are usually cleared from circulation by binding to a yet unidentified receptor-like protein on the surface membrane of erythrocytes, independently from complement or antibodies. The binding kinetics of DNA and other nucleic acids to erythrocytes are significantly altered in SLE patients, showing an overall reduced binding capability and presaturated binding kinetics. Significant amounts of chromosomal DNA can be isolated from erythrocytes of SLE patients but not from normal controls. Electron microscopy shows electron-dense particles on the surface of SLE erythrocytes (approximate size 20-40 nm). Comparative genomic hybridization reveals that the nucleic acid isolated from erythrocytes of SLE patients is of genomic and random origin, leading to an accumulation of "free" nucleic acids in the periphery, which eventually induces a B-cell immune response.

Antibodies↗
PubMed2000

FISH analysis of gene aberrations (MYC, CCND1, ERBB2, RB, and AR) in advanced prostatic carcinomas before and after androgen deprivation therapy.

Genetic mechanisms leading to androgen-independent growth in advanced prostatic carcinomas (PC) are still poorly understood. Analysis of genes potentially involved in the regulation of tumor cell proliferation and apoptosis might confer better insight into this process and might lead to improved therapeutic strategies. Fluorescence in situ hybridization (FISH) analysis of dissociated nuclei with DNA probes for MYC (8q24)/#8, cyclin D1 gene (CCND1; 11q13)/#11, ERBB2 (17q13)/#17, the androgen receptor gene (AR; Xq12)/#X, and the retinoblastoma gene (RB; 13q14) was applied to formalin-fixed tissue from 63 patients with advanced PC after androgen deprivation therapy (ADT); matched tumor tissue before ADT was also available in 22 of these cases. The cut-points used were: "increased copy number," > or = 30% of all nuclei with increased FISH signals (centromere and/or gene); "amplification," > or = 15% of nuclei with "increased gene copy number." CCND1 and MYC gene "amplifications" were present before ADT in 25% and 33% of the cases, respectively; the frequency of these "amplifications" increased to 37% and 57% after ADT. Loss of the RB gene was nearly four times more frequent after ADT than before therapy (22% versus 6%). AR and ERBB2 gene "amplifications" occurred only after ADT in 36% and 30% of cases, respectively. With the exception of the AR gene, the copy number increase was low. After treatment, MYC and AR gene "amplifications" correlated with the proliferation rate (Ki-67/MIB1 index; p = 0.01 and p = 0.04), whereas ERBB2 "amplifications" were associated with increased apoptotic index (PCD/TUNEL; p = 0.016). However, no correlation between FISH results and clinical follow-up could be established. FISH analysis of genes putatively involved in PC progression revealed characteristic patterns of aberrations in advanced PC before and after ADT. Distinct changes in gene copy number before and after therapy suggests possible involvement of these genes in the escape from androgen control.

Aged↗
PubMed2000

Sjögren's syndrome and MALT lymphomas of salivary glands: a DNA-cytometric and interphase-cytogenetic study.

Few and conflicting cytogenetic data are available concerning the chromosomal constitution of (mainly gastric) extranodal marginal zone B-cell non-Hodgkin's lymphoma arising from mucosa-associated lymphoid tissue (MALT)-type lymphoma. The majority of salivary gland MALT lymphomas are thought to develop from longstanding Sjögren's syndrome/benign lymphoepithelial lesion (BLEL). We tried to achieve a better comprehension of related cytogenetic alterations by comparing DNA-ploidy and numerical chromosomal (#) aberrations, assessed by different techniques of DNA cytometry (image cytometry) and interphase cytogenetics using nonradiographic in situ hybridization (centromere specific probes for #3, 7, 12, 18) on 12 cases of BLEL, 13 low-grade MALT lymphomas (LG-MALT-L) and 4 high-grade MALT lymphomas (HG-MALT-L) of salivary gland. Both techniques were applied on tissue sections preferentially, enabling a reliable measurement of histomorphologically identified areas. No case of BLEL showed cytogenetic abnormalities. Three of 4 HG- and 2 of 13 LG-MALT-L exhibited complex chromosomal gains in nonisotopic in situ hybridization, which were reflected by DNA nondiploidy in image cytometry. In 6 of 13 LG- and lof 4 HG-MALT-L, one or two numerical chromosomal aberrations were demonstrated by nonisotopic in situ hybridization, which could not be resolved by image cytometry. In the 11 DNA-diploid LG-MALT-L, trisomies 18, 3, and 12 were found in 36, 12, and 9%, respectively. In conclusion, comparing BLEL, which showed no chromosomal aberrations, with LG- and HG-MALT-L, an increase in frequency and number of numerical aberrations and DNA nondiploidy was seen. Peritetraploid DNA nondiploidy might be characteristic for HG-MALT-L of salivary gland as it is a rare finding in MALT lymphomas of other sites. It is unclear whether the documented chromosomal aberrations in LG-MALT-L, especially increased rate of trisomy 18, indicate a pathogenic impact or merely reflect genetic instability.

Adult↗
PubMed1999

Microsatellite instability and loss of heterozygosity in prostatic carcinomas: comparison of primary tumors, and of corresponding recurrences after androgen-deprivation therapy and lymph-node metastases.

BACKGROUND: The molecular mechanisms leading to prostate cancer progression are poorly understood. In particular, those changes which are responsible for androgen-independent growth and metastatic spread in prostate cancer are an issue of current investigations. METHODS: To gain more insight into these processes, paired microdissected samples from both untreated, locally advanced primary tumors (n = 20) and recurrences (n = 20) after conventional androgen-deprivation therapy (ADT) were analyzed retrospectively for microsatellite instability (MSI) and loss of heterozygosity (LOH) at nine loci on chromosomes 8, 18, and X by polymerase chain reaction. In parallel, 12 prostatic carcinomas treated by radical prostatectomy and nine corresponding lymph-node metastases were analyzed in the same way. RESULTS: The group treated with ADT showed a total of 10 MSI in 7 of the primary tumors (35%): 4 of these (20%) at one locus, and 3 of these (15%) at two loci. In the recurrences, MSI was observed in 4 cases (20%): 3 of these at one locus (15%), and 1 of these (5%) at two loci. LOH was found in 8 cases (40%) before as well as after ADT. In the radically resected carcinomas, MSI could be detected at two chromosomal loci in one of the primary tumors (8%) and in one of the metastases (11%); LOH was found in 2 primaries (16%) and 3 metastases (33%). CONCLUSIONS: Although MSI can be found in advanced prostatic carcinomas, it apparently does not play a major role in the progression of prostate cancer regarding androgen-independent growth or lymphogenous spread.

Aged↗
PubMed1999

In serous ovarian neoplasms the frequency of Ki-ras mutations correlates with their malignant potential.

We analysed 44 tissue samples from serous ovarian neoplasms of different malignant potential for Ki-ras mutations by denaturing gradient gel electrophoresis (DGGE) and direct sequencing after microdissection. Point mutations at codon 12 were found in 7 of 20 tumours of low malignant potential (LMP) (35%) and in 2 of 6 well-differentiated carcinomas (33%). In contrast, no mutations were detected in the 11 poorly differentiated ovarian carcinoma samples or in the 7 serous cystadenomas. The frequency of Ki-ras mutations in serous ovarian tumours seems to correlate with the malignant potential of the neoplasms. The data favour the hypothesis of a de novo development of poorly differentiated ovarian carcinomas and do not support an evolution from LMP tumours or well-differentiated carcinomas.

Adult↗
PubMed1999

Lymphoepithelial duct lesions in Sjögren-type sialadenitis.

It is not clear, whether the so-called basal cells of the salivary striated ducts are an independent cell-type distinct from myoepithelial cells, making characterization of the cell proliferation typical of the duct lesions in Sjögren-type sialadenitis/benign lymphoepithelial lesion (BLEL) difficult. An immunohistochemical investigation including different cytokeratin subtypes, alpha-actin, Ki-67 and Bcl-2 was directed at the epithelial cytoskeleton in normal parotid parenchyma (n=8), BLEL (n=12), HIV-associated lymphoepithelial cysts (n=8) and palatine tonsils (n=8). There are profound morphological and functional differences between basal and myoepithelial cells in the normal salivary duct. Development of duct lesions in BLEL arises from basal cell hyperplasia of striated ducts with aberrant differentiation into a multi-layered and reticulated epithelium, characterized by profound alteration of the cytokeratin pattern. This functionally inferior, metaplastic epithelium is similar to the lymphoepithelial crypt epithelium of palatine tonsils. The often postulated participation of myoepithelial cells in duct lesions of Sjögren disease/BLEL cannot be supported. We regard the designations lymphoepithelial lesion and lymphoepithelial metaplasia as the most appropriate.

Adolescent↗
PubMed1999

Prognostic importance of the expression of CD44 splice variants in oral squamous cell carcinomas.

Considering squamous cell carcinomas (SCCs) of the oral cavity and oropharynx the molecular mechanisms underlying the infiltration and destruction of adjacent tissue as well as the metastatic spread are largely unknown. In this context, the detection of defective expression of cellular adhesion molecules in the tumour cells, e.g. CD44, might be important and correlated with prognosis. Paraffin-embedded tumour-tissue from 99 patients with primary oral and oropharyngeal SCC, additionally including corresponding lymph-node metastases in nine cases, was analysed for expression of the CD44 splice variants v4, v5, v6, v7, and v9 by means of immunohistochemistry. A diminution of at least one of the examined CD44 isoforms compared to the normal oral epithelium was observed in 39.4% of the squamous cell carcinomas. No correlations could be found between CD44 expression and pT- or pN-stage. However, decreased expression of v9 was correlated with higher histological grade (p < 0.001). Moreover, reduced CD44 expression was a statistically significant independent predictor for shorter survival time (p = 0.002) as well as shorter recurrence-free interval (p = 0.004) in addition to pT- and pN-stage. The separate analysis showed that particularly the decreased v7 (p = 0.04) and v9 (p < 0.02) expression in the tumour cells was associated negatively with survival.

Adult↗
PubMed1999

Proliferation- and apoptosis-associated factors in advanced prostatic carcinomas before and after androgen deprivation therapy: prognostic significance of p21/WAF1/CIP1 expression.

The molecular mechanisms leading to androgen-independent growth in prostate cancer (PC) are poorly understood. Androgen deprivation therapy (ADT) results physiologically in a decrease in proliferation and an increase in programmed cell death (PCD)/apoptosis. The aim of our study was to get more insight into these processes in prostatic carcinomas before and after ADT. For this purpose, immunohistologic staining for the androgen receptor (AR) molecule, the Ki-67 antigen, the bcl-2 oncoprotein, the p53 protein and its physiologic effector, p21/WAF1, was performed on archival material. PCD was visualized by enzymatic detection of DNA fragmentation. Specimens from 69 PC patients after ADT were studied in correlation to histopathology and prognosis. In 42 cases, corresponding tumour tissue from the untreated primary tumours could be analysed comparatively. Before ADT, histologic grade was associated with Ki-67 index (P < 0.0001, Spearman correlation) and PCD rate (P < 0.05, Spearman correlation). Ki-67 index correlated with PCD rate (P < 0.05, Spearman correlation) and p21/WAF1 expression (P < 0.01, Fisher's exact test). p21/WAF1 expression was the only statistically significant prognostic factor for shorter survival (P < 0.002, log-rank test). All p21/WAF1-positive cases showed high Ki-67 index and high histologic grade. After ADT, loss of AR expression was associated with high Ki-67 index, whereas histologic signs of regression correlated negatively with Ki-67 index (P < 0.001, Pearson chi2 test). p21/WAF1 expression increased significantly (P < 0.02, McNemar test) and correlated with p53 accumulation (P < 0.0001, Pearson chi2 test). Most significant prognostic parameter after conventional ADT was high-rate p21/WAF1 expression (> 50% of tumour cells; P < 0.00001, log-rank test). This study demonstrates that p21/WAF1 overexpression before and after ADT characterizes a subgroup of advanced PC with paradoxically high proliferation rate and significantly worse clinical outcome. This finding might be clinically useful for planning therapy in these patients.

Aged↗
PubMed1999

Paraneoplastic pemphigus with fatal pulmonary involvement in a woman with a mesenteric Castleman tumour.

A 42-year-old woman presented with oral and labial erosions, conjunctivitis, facial rash and lichenoid erythematous papules on the trunk. Paraneoplastic pemphigus (PNP) was suspected, and a search for a neoplasm revealed an intra-abdominal Castleman tumour sized 7 x 5 x 6 cm. After removal of the Castleman tumour, the skin and mucosal inflammation gradually subsided over the next 12 months. However, due to irreversible pulmonary involvement the patient died of intractable respiratory distress 2 years after the onset of the disease. Systemic corticosteroids, azathioprine, cyclophosphamide, high-dose intravenous immunoglobulins and thalidomide were ineffective. The diagnosis of PNP was confirmed by keratinocyte antigen immunoprecipitation with the patient's serum.

Adult↗
PubMed1999

Microsatellite analysis in serous tumors of the ovary.

Thirty-four serous ovarian neoplasms were analyzed for microsatellite instability (MIN) and loss of heterozygosity (LOH) at 20 chromosomal loci of eight different chromosomes, including the map positions of the six known mismatch repair genes. Twelve of the 20 (60%) serous ovarian tumors of low malignant potential (LMP) and 13 of 15 (87%) samples of serous ovarian carcinomas, taken from 14 patients, showed LOH at one or more of the analyzed microsatellite loci. In serous carcinomas, LOH of the dinucleotide repeat D7S521 was most frequent. Six of 20 (30%) LMP tumors were also affected by MIN at more than one locus, whereas in the carcinomas MIN was found only sporadically (p < 0.025). No correlation between increased occurrence of MIN and LOH at the chromosomal loci of the known mismatch repair genes were discovered for these LMP tumors. Although our observation regarding LOH frequency in serous LMP tumors and serous carcinomas is compatible with the hypothesis that serous LMP tumors might represent precursor lesions of invasive carcinomas, the results concerning the occurrence of MIN suggest that the mechanisms of tumorigenesis of some tumors of LMP are distinct from those in invasive serous carcinomas.

Aged↗