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U Löhrs

Publications and source records attributed to U Löhrs.

At least 19 recordsLinked to original sources
PubMed2006

HER-2/neu gene amplification in ovarian tumours: a comprehensive immunohistochemical and FISH analysis on tissue microarrays.

AIMS: Data on HER-2/neu overexpression, its correlation to prognosis and the success of treatment with Herceptin((R)) in ovarian carcinomas are scarce and contradictory. Therefore we assessed HER-2/neu expression and amplification in a large series of ovarian tumours by using tissue microarrays (TMAs). METHODS AND RESULTS: Two TMAs containing 173 invasive carcinomas, 36 borderline tumours, 20 granulosa cell tumours, 14 carcinosarcomas, 11 benign cystadenoms and eight other pelvic tumours were constructed to assess HER-2/neu gene amplification by fluorescence in-situ hybridization (FISH) and immunohistochemistry. Immunohistochemistry was successful in 94.3%; 81.8% were HercepTest negative, 11.3% were scored as 1+, 4.1% as 2+ and 2.8% as 3+, including 3.1% of invasive carcinomas, 2.8% of borderline tumours and 7.7% of carcinosarcomas; 83.6% could be analysed successfully by FISH revealing no aberration in 75.8%, low amplification in 2.7% and high amplification in 3.7% of the cases. In 17.8% monosomy, trisomy, polysomy or deletion could be detected. All cases with high-level amplification had 2+ or 3+ scores on immunohistochemistry. CONCLUSIONS: TMA is a feasible tool to study a large number of ovarian cases. Correlation between immunohistochemistry and FISH was excellent. HER-2/neu overexpression or gene amplification does not correlate with histological tumour type, stage, grade or prognosis.

Adolescent↗
PubMed2005

Tumour size is an important predictor for the outcome after liver transplantation for hepatocellular carcinoma.

AIMS: Recently, there is a tendency to expand tumour sizes qualifying for OLT. The present study re-evaluates tumour size and histopathological features as selection criteria for OLT. METHODS: Retrospective analysis of 93 adult HCC patients underwent OLT between June 1985 and December 2003. Median follow-up was 28 months (1-222 months). The Milan criteria were routinely applied since 1994. RESULTS: Five year survival rate of HCC patients was significantly lower than in patients transplanted for benign diseases, 41 and 71%, respectively (p<0.0001). Multivariate analysis revealed that the presence of vascular invasion represents the most significant predictor (p<0.001) affecting the survival rate. Survival was also significantly impaired when the tumour size was >5 cm (p<0.05), whereas the number of nodules had no significant effect on survival. Consequently, the survival rate for HCC fulfilling the Milan criteria histologically improved to 70% since 1994. CONCLUSION: Tumour size has been shown to be the most important pre-operatively detectable predictor for patient survival after OLT.

Adolescent↗
PubMed2004

[Chronic circumferential aortic dissection with intimo-intimal intussusception].

A circumferential aortic dissection with so-called intimo-intimal intussusception is a very rare complication of a dissecting aneurysm, in which the sock-like intimal flap is upended in the true lumen by the blood stream. The few cases reported thus far are based on radiological or intraoperative findings in acute dissections. The present postmortem study documents the very rare case of long-term survival of a chronic circumferential dissection with intimo-intimal intussusception.

Aortic Dissection↗
PubMed2004

Analysis of HER-2/neu amplification in endometrial carcinoma by chromogenic in situ hybridization. Correlation with fluorescence in situ hybridization, HER-2/neu, p53 and Ki-67 protein expression, and outcome.

Fluorescence in situ hybridization (FISH) is the most widely used technique to detect HER-2/neu gene amplification; however, it is only available in some institutions. In contrast, chromogenic in situ hybridization (CISH) can be evaluated by routine light microscopy. In endometrial carcinoma there are few data concerning HER-2/neu status and prognosis. Therefore, we determined HER-2/neu gene status by CISH using a digoxigenin-labelled probe on 60 formalin-fixed paraffin-embedded endometrial carcinomas. The data were compared with the immunohistochemistry of HER-2/neu (A0485, TAB250), p53, Ki-67, clinicopathological factors, and survival. By conventional light microscopy, HER-2/neu amplification (>/=6 copies >50% cancer cells) was detected in 14% (8/59) tumours, HER-2/neu overexpression (>10% cells moderate/strong complete membrane staining) in 22% (13/60) for A0485, and 18% (11/60) for TAB250, p53 (>10% +cells) in 61% (36/59), and Ki-67 (>50% +cells) in 50% (30/60). Discordant cases for CISH and immunohistochemistry, as well as all (2+) were further analysed by FISH (Vysis). Among 10 cases (2+) and not amplified by CISH, two showed low-level amplification by FISH. Significant correlation was found between amplification and protein overexpression (P</=0.001), and a trend with nonendometrioid type, higher grade, and older age. A better outcome (Kaplan-Meier) was observed for patients with nonamplified (1-5 copies per nucleus) or low-level (6-10 copies) amplification tumours, low Ki-67 expression, age <50 years, endometrioid type, low FIGO (International Federation of Obstetrics and Gynaecology) grade and stage, superficial myometrial infiltration, and no lymph-vascular invasion (P</=0.036), but only as a trend for HER-2/neu protein negative (P=0.13). Cox analysis revealed age, FIGO grade and stage, myometrial infiltration, and lymph-vascular invasion to be independent prognostic factors (P</=0.05), and a trend for HER-2/neu gene copy number (0.18). In endometrial carcinoma, HER-2/neu gene status can be readily assessed by CISH in routine clinical practice, and it gives more prognostic information than HER-2/neu by immunohistochemistry. FISH analysis in (2+) cases but negative by CISH may detect additional tumours with low-level amplification.

Adult↗
PubMed2004

Prognostic relevance of 20q13 gains in sporadic colorectal cancers: a FISH analysis.

BACKGROUND: Amplification of 20q13 is a frequent chromosomal alteration in solid tumors and harbors a number of putative oncogenes (CAS/CSE1-L, NABC1, or Aurora2). Amplifications on 20q13 have been identified as an independent prognostic marker indicating worse survival in breast and ovarian cancer. However, little is known about the prognostic significance of 20q13 gains in sporadic colorectal cancers. The aim of this study was to correlate 20q13 gains in sporadic colorectal cancers with other known prognostic factors, tumor progression, and overall survival. METHODS: Nuclei were extracted from 146 paraffin-embedded colorectal cancers of different UICC stages and used for fluorescence in situ hybridization (FISH) with a directly labeled probe for 20q13.2 (VYSIS). Signals were counted in 120 nuclei per sample. 20q13 was considered gained when > or =40% of the nuclei showed 3 or more FISH signals. Statistical correlations were tested with log-rank tests and Kaplan-Meier survival curves. RESULTS: Signal numbers for 20q13.2 were gained in 78 cases (53%). Cases with gains on 20q13.2 showed worse outcome than cases without: the gain of 20q13.2 was an independent prognostic marker for overall survival (P=0.006) as well as tumor progression (P=0.012) in univariate and multivariate analyses. Gains on 20q13.2 did not correlate with tumor stage. However, there was a significant association between 20q13.2 gains and tumor location in the left-sided colon and an inverse correlation between histologic grade and 20q13.2 gains. CONCLUSION: These data indicate that gains on 20q13.2 correlate with faster tumor progression and worse patient survival independent from tumor size and lymph node involvement. Therefore, alterations on 20q13 are an important biological event in colorectal tumor progression with independent prognostic relevance.

Adenoma↗
PubMed2003

[Adrenal adenomatoid tumor. A rare clinicopathological entity].

Adenomatoid tumors are uncommon, benign tumors of the genital tract which have also been reported to occur extragenitally. Case reports on adenomatoid tumors of the adrenal gland exist. Most of these are incidentally discovered at autopsy or after the resection of incidentalomas. We report on the case of a young man with epigastic pain and with the finding of a 4 cm heterogeneous right adrenal mass on abdominal CT scan. After endocrine activity had been ruled out, an inactive, benign adrenal tumor was suspected and laparoscopic right adrenalectomy performed. The specimen was found to be an adenomatoid tumor. We discuss the differential diagnosis and the possible embryological origin of these tumors. The feature of 'local invasive ability' does not imply malignancy. All cases discovered surgically and at autopsy have been benign. Local resection seems to be the appropriate therapy.

Adenomatoid Tumor↗
PubMed2003

[Hepatitis of unknown origin with protracted liver failure in a 48-year-old patient with significantly increased pANCA titer].

In spite of intense diagnostic testing, no cause for the chronically aggressive hepatitis of a 48-year old male patient was found. Evidence for an autoimmune process, however, could be derived from a high titer of pANCA. Only according to the revised criteria of the working group on autoimmune hepatitis, but not to the first version, it was possible to classify this as an autoimmune hepatitis. Despite of high-dose steroid treatment and accelerated preparation for liver transplantation the patient died of the complications of rapid liver failure. Thus, in case of unclear rapid progressive hepatitis, the revised criteria of autoimmune hepatitis should be reviewed early and with high priority and consequent high-dose steroid therapy and preparation for liver transplantation should be initiated. The prognostic impact of a high titer of pANCA in patients with autoimmune hepatitis remains to be established.

Antibodies, Antineutrophil Cytoplasmic↗
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

Inverse relation of Fas-ligand and tumor-infiltrating lymphocytes in angiosarcoma: indications of apoptotic tumor counterattack.

Fas and Fas-L regulate immune responses through the induction of cell death. Fas-L is commonly expressed in activated immune cells and in the endothelium. In the latter it contributes to the inhibition of transvascular cell migration by the induction of apoptosis in Fas-bearing lymphocytes. Here we investigated whether the Fas/Fas-L system may regulate lymphocyte invasion into angiosarcomas. Fas and Fas-L expression was quantitatively determined in different grade angiosarcomas (n = 40) and related to the number of extravasated tumor-infiltrating lymphocytes (TILs). Fas expression was detected in < 50% of the cases. In positive tumors both the number of Fas-positive cells and the staining intensity were highly variable and did not correlate with the number of TILs, the mean time of survival, and the histopathological tumor grade. By contrast, Fas-L expression was detected in >70% of the cases and the relative numbers of Fas-L-positive cells correlated inversely with the numbers of CD3- and CD8-positive TILs (P < or = 0.004). The survival times of patients with high Fas-L-expressing angiosarcomas were significantly reduced as compared to patients with low Fas-L-expressing tumors. Our results show that angiosarcomas with low Fas-L expression are characterized by numerous TILs, whereas sarcomas with high Fas-L expression show significantly reduced numbers of TILs. These results suggest that the Fas/Fas-L system may repress TIL invasion into angiosarcoma and by this may contribute to the evasion of the anti-tumor immune surveillance of angiosarcoma in the course of an apoptotic tumor counterattack mechanism.

Adult↗
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

Prognostic relevance of hMLH1, hMSH2, and BAX protein expression in endometrial carcinoma.

Endometrial carcinoma is the most common gynecologic malignancy in perimenopausal and postmenopausal women. A role of mismatch repair genes, like hMLH1 and hMSH2 in their pathogenesis, has been suggested. Loss of their function leads to the accumulation of replication errors (mutator phenotype), which are responsible for further mutations in genes with microsatellite sequences in their coding region, such as Bax. We analyzed the expression of hMLH1, hMSH2, and Bax genes in 89 formalin-fixed paraffin-embedded endometrial carcinomas. The immunostains were scored with regard to percentage of positive tumor cells (0%, <10%, 10 to 50%, >50%), and relative staining intensity (1+, 2+, 3+). The staining results were correlated with clinicopathologic features and survival. Loss of hMSH2 expression (0% positive cells) was observed in 1.1% (1/89) of the tumors; loss of hMLH1 was seen in 12.4% (11/89) of the cases, particularly in endometrioid tumors with mucinous differentation (5/11; 45%; P =.03). No significant association was found between the immunoscores and grade, stage criteria of the International Federation of Obstetrics and Gynecology (FIGO), or age of the patients. Among 11 tumors with loss of Bax expression (12.4%), 4 had also loss of hMLH1 (4/11; 36.4%; P =.017). In multivariate analysis (Cox model), significantly longer survival was found for patients with tumors in FIGO Stage I-II (P <.0001), endometrioid type (P =.001), low grade (P =.001), and absence of hMLH1 expression (P =.027). Our results suggest that loss of function of hMLH1 and Bax occur in a subgroup of endometrial carcinoma. In addition to the classical prognostic factors, absence of hMLH1 expression is associated with better outcome of patients.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Cellular apoptosis susceptibility gene expression in endometrial carcinoma: correlation with Bcl-2, Bax, and caspase-3 expression and outcome.

Deregulation of proliferation and apoptosis is known to contribute to neoplastic transformation and growth. Using specific antibodies for the cellular apoptosis susceptibility (CAS) gene, caspase-3, Bcl-2, and Bax, we examined the protein expression in 89 endometrial carcinomas and in 56 samples of nonneoplastic adjacent endometrium for comparison. Immunostaining results were scored with regard to approximate percentage of positive tumor cells (< 10%, 10% to 50%, > 50%) and relative immunostaining intensity (1+, 2+, 3+). In nonneoplastic endometrium, CAS protein was expressed in 70.6%, Bax in 64%, caspase-3 in 52%, and Bcl-2 in 87%. In neoplastic tissue, CAS was present in 93% of the tumors, Bax in 88%, caspase-3 in 77%, and Bcl-2 in 51%. Bcl-2:Bax ratio was > 1 in 9 cases (10%). In cases of atrophy (n = 24) and simple (n = 10) and complex (n = 22) hyperplasia in the adjacent endometrium, lower levels of expression compared with carcinoma were observed for CAS (p = 0.003), caspase-3 (p = 0.034), and Bax (p = 0.04) and higher levels for Bcl-2, although for this protein the results were not statistically significant (p = 0.32). There was no association between immunoscores and FIGO stage. High caspase-3 levels were seen in endometrioid tumor type (p = 0.017). CAS expression was higher in grade 3 tumors (p = 0.002) and older patients (p = 0.013). All tumors of younger patients (< 50 years) were Bcl-2 negative (p = 0.037). Caspase-3 correlated positively with CAS (p = 0.008), Bax (p = 0.04), and low Bcl-2:Bax ratio (p = 0.043), and inversely (as a trend) with Bcl-2 (p = 0.056). Survival analysis (Kaplan-Meier and Cox regression) established a strong association between prognosis and stage, grade, and histologic type (all p < or = 0.0036). In addition, shorter survival was observed for patients whose tumors contained > 50% of positive cells for caspase-3 (p = 0.024) or for CAS (p = 0.04). Age, Bcl-2, Bax, and Bcl-2:Bax ratio did not provide prognostic information. Our results suggest a role of CAS, Bcl-2, Bax, and caspase-3, which are apparently involved in the progressive deregulation of proliferation and apoptosis leading from simple and complex hyperplasia to carcinoma. In addition, CAS and caspase-3 protein levels may be useful markers in predicting the outcome of the patients.

Adenocarcinoma, Mucinous↗
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↗
PubMed2001

[Pathology in so-called Problem Oriented Learning (POL)].

UNLABELLED: Within the evolutionary progress in biomedical research and clinical medicine the medical education plays a derminting role. Problem based learning (PBL) or problem oriented learning (POL), respectively, are main though not quite new topics in the international discussion about modern teaching in medicine. After shortly reviewing the principles of PBL the problems of this concept in general and in the special situation of the Medical Schools of German Universities bound to legal rules and with high numbers of students are discussed with special regard to Pathology representing a substantially central teaching discipline. At the Medical School of the University of Munich since 1997 the so-called Münchner Modell (Munich Model) has been successfully established representing a hybrid curriculum with integration of PBL courses and traditional forms of teaching. The experience with special regard to the participation of Pathology is discussed. IN CONCLUSION: Modern scientific medicine requires an adequate teaching and learning culture. PBL is one main concept possibly to be integrated. In the future Pathology will continuously play a central role in medical teaching because of its imminent potential. Permanent reflecting the usefulness of modern teaching proposals and critical engagement are prerequisites.

Education, Medical↗
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↗