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  • 1
    ISSN: 1434-3940
    Keywords: Schlüsselwörter Plattenepithelkarzinome der Kopf-Hals-Region (KHPEK) ; p53 ; HPV ; Überlebensrate ; Key words Head and neck squamous cell carcinoma (HNSCC) ; p53 ; HPV ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Mutations of the p53 gene are the most commonly observed genetic alterations in malignant tumors and are often associated with a loss of the tumor suppressor function of the p53 protein. We have analyzed specimens of head and neck squamous cell carcinomas (HNSCC) from 110 patients for p53 gene mutations and 92 of them additionally for human papillomavirus (HPV) infection in order to evaluate the prognostic significance of these factors by comparison with clinical follow-up data. Using the method of polymerase chain reaction (PCR) / temperature gradient gel electrophoresis (TGGE), mutations within the exons 5 to 8 of the p53 gene were found in 48 tumors (44%). Sequencing revealed missense mutations in most cases (15/20). Frequency of p53 gene mutations was not related to the tumor stage, the grade of differentiation, the presence of lymph node metastases, or the smoking history of the patients. With the help of a highly sensitive PCR/hybridization assay, an infection with the high-risk HPV types 16 and 18 could be detected in 39/92 tumor specimens (42%). Follow-up data were obtained from 99 patients with a range of 2– 112 months. No correlation of overall survival on the presence of p53 gene mutations or HPV infection could be observed. The absence of statistically significant correlations between p53 gene mutations and progressive disease, however, does not exclude its putative relevance in early phases of tumor development.
    Notes: Es wurden Tumorgewebsproben von 110 Patienten mit Plattenepithelkarzinomen der Kopf-Hals-Region (KHPEK) untersucht. Mit Hilfe der Polymerasekettenreaktion (PCR) und anschließender Temperaturgradientengelelektrophorese (TGGE) konnten in 48/110 Tumoren (44%) Mutationen in den Exons 5–8 des p53-Gens nachgewiesen werden. Die Sequenzierung der PCR-Produkte ergab in den meisten Fällen Missense-Mutationen. Die Mutationshäufigkeit korrelierte nicht mit dem Tumorstadium, dem Differenzierungsgrad der Tumoren, dem Lymphknotenstatus oder dem Tabakkonsum der Patienten. Infektionen mit den High-Risk-HPV-Typen 16 und 18 zeigten 39/92 Tumoren (42%). Die Gesamtüberlebensrate der Patienten korrelierte nicht mit der p53-Mutationsfrequenz und der HPV-Infektionsrate. Das Fehlen einer statistisch signifikanten Korrelation mindert jedoch nicht die mögliche Bedeutung dieser Faktoren für die frühen Phasen der Tumorentstehung.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2307
    Keywords: Keywords MUC2 ; MUC5AC ; ACIS ; Adenocarcinoma ; Tubal metaplasia ; Endometriosis ; Cervix uteri
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The expression of mucin genes in the normal glandular epithelium of the endocervix has been well characterized. However, mucin gene expression in neoplastic or particular non-neoplastic glandular cervical lesions has not been addressed. This immunohistochemical study was carried out to analyze the expression of MUC2 and MUC5AC in neoplastic and non-neoplastic glandular lesions of the cervix. Monoclonal antibodies were used on paraffin-embedded sections from 41 adenocarcinomas, 2 adenosquamous carcinomas, 13 adenocarcinomas in situ (ACIS), 3 glandular dysplasias, 8 endometrioses, 5 tubal metaplasias, 17 squamous metaplasias, 3 microglandular hyperplasias and normal tissue of the endocervix, endometrium and fallopian tube. The patterns of expression of MUC2 and MUC5AC were different and in principle contrary. Focal MUC2 expression was observed almost exclusively in neoplastic lesions (36%) and not in normal epithelia and non-neoplastic lesions, the one notable exception being immature metaplasia. In contrast, strong expression of MUC5AC was observed in both normal endocervical epithelium (100%) and neoplastic lesions (73%). The expression of MUC5AC, however, was diminished in most neoplastic glandular lesions. Co-expression of MUC2 and MUC5AC was consistently documented in the lesions with intestinal differentiation. In contrast, cases of tubal metaplasia and endometriosis were negative for MUC2 and MUC5AC. These results indicate that discrimination of mucin gene expression may be helpful in discriminating lesions of the cervix.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 6 (2000), S. 1022-1033 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Während das Plattenepithelkarzinom der Vulva eine konstante Inzidenz aufweist, lässt sich für die vulväre intraepitheliale Neoplasie (VIN) eine steigende Häufigkeit nachweisen. Diese gründet sich auf die wachsende Infektionsrate mit den in einem Teil der Fälle pathogenetisch bedeutsamen Humanen Papillomaviren (HPV). Hinsichtlich der klinischen Therapieplanung sowie der prognostischen Einschätzung ist eine histopathologische Differenzierung der präneoplastischen und neoplastischen Erkrankungen der Vulva unerlässlich. Gleiches gilt für maligne Erkrankungen der Vagina, wobei hier insbesondere primär vaginale Tumoren von metastatischen Absiedelungen zu unterscheiden sind. Für den klinisch-onkologisch tätigen Arzt ist aus diesen Gründen die Kenntnis histopathologischer Kriterien zur Interpretation der ihm übermittelten Befunde hilfreich.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2307
    Keywords: Key words Breast cancer ; Extracellular matrix ; MMP ; TIMP ; Extracellular matrix degradation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Invasive growth requires degradation of extracellular matrix. Altered expression of matrix degrading enzymes may indicate an increased potential for invasive growth. We determined the expression patterns of matrix-metalloproteinases (MMP)-1, -2, and -3 and of the tissue inhibitors of metalloproteinases (TIMP)-1 and -2 by in situ hybridization with isotopically labeled RNA probes in normal breast tissue (n=6), fibrocystic disease (n=20), five cases of which contained radial scars, lobular carcinoma in situ (CLIS; n=5), ductal carcinoma in situ (DCIS; n=9) and invasive carcinomas (n=24). Only a few cells displayed MMP-1- and MMP-2-specific labeling in normal breast tissue and fibrocystic disease. Noninvasive ductal carcinomas showed elevated MMP-2 transcript levels in peritumor stromal cells in the absence of significant MMP-1 specific signals. In general, compared with adjacent normal breast tissue, a gradual increase of MMP-2 was found in noninvasive to invasive cancers. Invasive ductal and lobular carcinomas displayed co-expression of MMP-1 and MMP-2 by stromal cells, mainly of the invasion front, with high signal intensity particularly in high-grade invasive carcinomas. Tumor cells and peritumor stroma showed low MMP-3 transcript levels, especially in medullary carcinomas. TIMP-1 and -2 transcript levels were increased in invasive carcinomas correlating with the histological grade. These RNA expression patterns suggest an increased invasive potential in breast carcinomas even prior to histologically overt invasive growth.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2307
    Keywords: p53 ; Endometrioid carcinoma ; Endometrial hyperplasia ; Temperature-gradient gel electrophoresis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to evaluate the presence and distribution of p53 alterations in pure endometrioid adenocarcinomas (n=120) of different grades and stages, as opposed to normal endometrium (n=13) and various risk groups of hyperplasia (n=39). All samples were initially analysed by immunohistochemistry with the monoclonal antibody Ab-6. Normal endometria were negative. With increasing degrees of malignancy, the number of cases with p53 accumulation rose and ranged from 9% to 18% in hyperplasia, through 25% in lowgrade carcinomas (G1), to 69% in high-grade carcinomas (G3). This increase was also seen when comparing tumours by stage. Of carcinomas in stage IA, only 17% showed p53 immunostaining, in contrast with 72% in stage IC. Of this material, 34 carcinomas and 8 hyperplasias were analysed for p53 mutations in exons 5–8 by means of polymerase chain reaction and temperature-gradient gel electrophoresis (TGGE). In none of 5 hyperplasia and 6 of 12 carcinomas showing p53 accumulation by immunohistochemistry, p53 mutations were detected by TGGE. In contrast, 4 of 22 carcinomas harboured mutant p53 but were negative by immunohistochemistry. Immunohistochemical and molecular investigations revealed that p53 alterations are related to the standard prognostic markers of endometrial cancer, i.e. grading and staging. TGGE, an indirect screening procedure for p53 mutations, is used to detect the type of p53 alteration and may provide additional insight into the complex figure of p53 abnormalities in the development and progression of malignant endometrial lesions.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 20 (1999), S. 9-14 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Endometriumkarzinom ; Zervixkarzinom ; Konus ; Hysterektomie ; Key words Cervical Carcinoma ; Endometrial carcinoma ; Konisation ; Loop excision ; Hysterectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Tumor classification, grading and staging of malignant tumors of the cervix and corpus uteri should be done according to the rules of the WHO fascicle of 1994 and the TNM manual of 1997, respectively. With these lines taking into account, the surgical pathology report will include the most important prognostic factors, which in part are also of therapeutic relevance, i.e. localization of the lesion, depth of invasion and distant tumor manifestation. Yet, gross inspection and preparation are the prerequisites of the quality of the histopathological statement. Accurate documentation of tumor extension, depth of invasion into the cervical stroma and/or the myometrium and distance to the resection lines at the vaginal cuff and the parametrium needs to be given in centimeters, first by eye, than controlled by histopathology. The tumor extension of cervical carcinomas should be given in three dimensions, including the depth of invasion into the cervical wall. It is also mandatory to document the number and size of lymph nodes with metastatic involvement compared to the total number of nodes which are discovered in parametral, pelvioperitoneal and paraaortal sites. Most of what has been outlined for the surgical pathology report of hysterectomy specimens is also pertinent to conisations, by whatever method these are performed (cold knife, laser or loop). For appropriate documentation of the localization of the lesion, horizontal expansion of the dysplastic lesion and recognition of microinvasion it is sufficient to dissect the conisation specimen clockwise and to cut the various paraffin blocks in serial sections.
    Notes: Zusammenfassung Die Tumorklassifikation und das Grading des Zervix- und Endometriumkarzinoms richten sich nach der WHO Einteilung von 1994, das Staging nach der TNM-Klassifikation von 1997. Darin sind die prognostisch und z.T. auch therapeutisch bedeutsamsten Faktoren wie die Tumorlokalisation, die Invasionstiefe und evtl. organübergreifendes Tumorwachstum enthalten. Die wichtigste Voraussetzung für einen adäquaten histopathologischen Befundbericht ist die systematische Makropräparation und Begutachtung des Operationspräparates. Besonderes Augenmerk ist auf die metrischen Angaben zur Tumorausdehnung, relativen Invasionstiefe und zum Abstand zu den Resektionsrändern (vaginal, parametran) zu legen. Das Zervixkarzinom sollte dreidimensional gemessen werden („Tumorvolumetrie”). Obligatorisch sind Angaben zur Zahl und Größe der Lymphknoten-Metastasen im Verhältnis zur Zahl der untersuchten Lymphknoten. Das gilt auch für die parametranen Lymphknoten. Auch bei Konisaten bzw. Loop-Exzisaten ist die Lokalisation und Ausdehnung der Läsion anzugeben (bei Dysplasien die horizontale Ausdehnung, beim mikroinvasiven Zervixkarzinom zusätzlich die Invasionstiefe). Für die Ermittlung dieser Angaben ist der segmentale Zuschnitt zu empfehlen. Diese Methode hat den Vorteil, daß Gewebe für die Durchführung zusätzlicher Untersuchungen erhalten bleibt.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 20 (1999), S. 42-49 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Zervixkarzinom ; Plattenepithelkarzinom ; Mikroinvasives Zervixkarzinom ; Key words Cervical carcinoma ; Squamous cell carcinoma ; Microinvasive cervical carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The clinical management of cervical carcinomas is solely based upon the FIGO-staging system. Therefore clinical staging is crucial for primary therapy of cervical carcinomas. Accurate morphologic evaluation of the surgical specimens completes the clinical staging and determines postoperative procedures and the individual prognosis. The most important morphologic prognostic factors include stromal invasion, vascular space involvement, tumor volume and surgical margins (pelvic recurrence, metastasic dissemination, survival). The prognostic and therapeutic importance of tumor biological markers is presently controversial. Radical surgical therapy (Wertheim-Meigs surgery) and primary or adjuvant pelvic radiation are currently the basic therapeutic modalities for invasive cervical carcinomas. The role of chemotherapy still needs to be defined. A less radical therapeutic approach is performed for microinvasive cervical carcinomas depending on the extent of stromal invasion, the presence of vascular space involvement and the surgical margins.
    Notes: Zusammenfassung Die Behandlung des histologisch gesicherten Zervixkarzinoms erfolgt unabhängig vom histologischen Typ stadienspezifisch. Das klinische Staging ist für die Wahl der primären Therapie des Zervixkarzinoms entscheidend. Nach operativer Therapie ist die morphologische Begutachtung des Operationspräparates die Grundlage für das endgültige Staging, das weitere postoperative Vorgehen und die Prognose. Besondere Bedeutung haben Stroma- und Gefäßinvasion, Tumorvolumen und Resektatrandbefund, da diese Parameter als die wichtigsten morphologischen Prognosefaktoren (Beckenrezidiv, Fernmetastasierung, Überleben) gelten. Tumorbiologische Marker und Nachweismethoden spielen für die Therapieplanung und Prognose bisher keine Rolle. Klassische Therapieprinzipien sind die radikale Hysterektomie nach Wertheim-Meigs und die primäre oder adjuvante Bestrahlung des Beckens. Die Rolle der Chemotherapie ist noch zu definieren. Bei mikroinvasiven Karzinomen ist ein differenziertes, weniger invasives Vorgehen in Abhängigkeit von den Faktoren Stromainvasion, Gefäßinvasion und Resektatrandbefund möglich.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 20 (1999), S. 34-41 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Zervixdysplasie ; Zervikale intraepitheliale Läsion ; Zervikale intraepitheliale Neoplasie ; Key words Cervical dysplasia ; Cervical intraepithelial lesion ; Cervical intraepithelial neoplasia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Diagnosis of cervical dysplasia is based on colposcopy, cytology and histology. In case of suspect cytology, the management (controls only, extended diagnosis by histology or therapy without additional histological control) is dependent on colposcopic findings.Biopsy or endocervical curettings are necessary in cases of suspect ectocervical findings or endocervical lesions, respectively. As a rule, HE staining is sufficient for histological diagnosis. Yet, additional prognostic information is obtained by HPV-analysis and DNA-cytometry. Grading of dysplasia should be done according to the most recent WHO/ISGYP criteria. The exact diagnosis as to the grading and extension of dysplasia is the prerequisite of an effective individually adjusted therapy. For ablative therapy, gynecologists have to focus their attention on modern organ preserving surgery strategies (loop-excision).
    Notes: Zusammenfassung Die Diagnostik zervikaler Plattenepitheldysplasien umfaßt die Kolposkopie, Zytologie und Histologie. Bei auffälliger Zytologie bestimmt der kolposkopische Befund, ob ein abwartendes Verhalten mit Befundkontrollen möglich ist, eine erweiterte Diagnostik mit histologischer Sicherung des Befundes notwendig erscheint oder ob die vorhandenen Informationen für eine Therapieentscheidung ausreichend sind. Für die diagnostische Gewebsentnahme suspekter ektozervikaler Läsionen ist die Knipsbiopsie geeignet. Endozervikale Befunde werden durch eine Zervixabrasio abgeklärt. Die HE-Färbung ist für die histologische Befundung in der Regel ausreichend. Zusätzliche diagnostische, differentialdiagnostische und prognostische Informationen sind durch HPV-Analytik, DNA-Zytophotometrie oder Immunhistochemie (Keratine, Proliferationsmarker) möglich. Die Graduierung der Dysplasie sollte entsprechend der gültigen WHO/ISGYP- oder CIN-Nomenklatur vorgenommen werden. Nur eine optimale Dysplasie-Diagnostik (Graduierung, Ausdehnung, HPV-Typisierung) ermöglicht eine effektive, individuell abgestimmte Therapie. Das gelingt in vielen Fällen nur in einer Dysplasiesprechstunde. Bei der ablativen Therapie ist ein Schwerpunkt auf die organerhaltende, ambulant mögliche Hochfrequenz-Chirurgie (Schlingen-Exzision) zu setzen.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 256 (1995), S. 39-41 
    ISSN: 1432-0711
    Keywords: Vaginitis ; Vaginal diseases ; Immunosuppression ; Kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report a case of vaginitis emphysematosa in an immunosuppressived renal transplant patient without detectable infection. Immunological factors may have been involved in the pathogenesis.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 256 (1995), S. 39-41 
    ISSN: 1432-0711
    Keywords: Key words: Vaginitis ; Vaginal diseases ; Immunosuppression ; Kidney transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We report a case of vaginitis emphysematosa in an immunosuppressived renal transplant patient without detectable infection. Immunological factors may have been involved in the pathogenesis.
    Type of Medium: Electronic Resource
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