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  • 1
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 17 cases of focal epithelial hyperplasia of the oral mucosa (FEH, Heck's disease) were investigated for the presence of human papillomavirus (HPV) nucleic acid sequences by means of in situ DNA hybridization using biotinylated DNA probes of HPV types 1, 6, 11, 13, 16, 18, and 32. Ten of 17 cases were positive for HPV 13 DNA in contrast to 6 of 17 positive cases obtained after application of the HPV 32 probe, with a double infection in one case. The results of our study suggest, that HPV 13 and HPV 32 are very specifically found in lesions of FEH and can be detected in a high percentage of cases using in situ hybridization.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We analyzed specimens of head and neck squamous cell carcinomas (HNSCC) from 110 patients for p53 gene mutations, and 92 of them for human papillomavirus (HPV) infection, in order to evaluate the prognostic significance of these factors by comparison with clinical follow-up data. Mutations within the exons 5 to 8 of the p53 gene were found in 48 tumors (44%). Sequencing revealed in most cases mis-sense mutations (16/21). Frequency of p53 gene mutations was not related to the tumor stage or the presence of lymph node metastases. Of the 46 tumors that were analyzed by immunohistochemistry. 26 stained positively (56%). The number of positively stained nuclei increased slightly with decreasing differentiation of the tumors, whereas no correlation was found between tumor stage and immunoreactivity. 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 within a range of 2 to 112 months. No dependence 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 mutation and progressive disease, however, does not deny its putative relevance in early phases of tumor development.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2307
    Keywords: Adenocarcinoma Adenocarcinoma in situ Cervix uteri HPV infection HPV 16 and HPV 18 E6/E7 oncogene expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. To evaluate the importance of high-risk human papillomavirus (HPV) types in in situ and invasive adeno- and adenosquamous carcinomas (ACISs/ACs, and ASCISs/ASCs) of the cervix uteri, we analyzed HPV infection and HPV 16- and HPV 18 E6/E7 oncogene expression in different histologic subtypes. Using the polymerase chain reaction (PCR) technique, 29 of 33 (88%) ACISs, 2 of 2 (100%) ASCISs, 46 of 54 (85%) ACs, and 8 of 10 (80%) ASCs were found to be HPV 16- and/or HPV 18-positive. In 25 of 35 (71%), 10 of 35 (29%), and 4 of 35 (11%) ACISs/ASCISs, HPV 16, HPV 18, and HPV 16 and HPV 18 were detected, respectively. Invasive ACs/ASCs were more frequently infected with HPV 18 (36 of 64, 56%) than with HPV 16 (28 of 64, 44%). Ten (16%) of these cases were positive for HPV 16 and HPV 18. In ACISs/ASCISs, HPV 16 oncogene expression predominated (62%) relative to HPV 18 (25%) expression, whereas in invasive ACs/ASCs, only 21% of the cases expressed HPV 16, but 48% of the cases expressed HPV 18 oncogenes. Thus, detection of HPV 18 in ACISs/ASCISs might be associated with an increased risk of progression. HPV oncogene expression was not dependent on histologic subtype of in situ or invasive AC. Normal glandular epithelia and glandular dysplasias (GDs, n=4) were always negative concerning HPV oncogene expression. In HPV 16- and HPV 18-double-infected cases, HPV 18 oncogene expression was most frequently detected, and we did not find a coexpression of HPV 16- and HPV 18-specific oncogenes in purely glandular lesions or in cases with an additional CIN (cervical intraepithelial neoplasia) II or CIN III. HPV E6/E7 expression of the same HPV type in both in situ or invasive ACs and associated CIN II/III suggest that these lesions might be histogenetically related.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 384 (1979), S. 109-120 
    ISSN: 1432-2307
    Keywords: Plasma cell ; Immunoglobulins ; Leukoplakia ; Squamous cell carcinoma ; Tumor therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The subepithelial and peritumoral inflammatory infiltrates of 202 oral premalignant and malignant lesions — 108 leukoplakias and 94 squamous cell carcinomata with different grades of dysplasia were examined using an immunoenzymatic method. In addition, the influence of radiation and bleomycin-therapy on the stromal reaction of 24 carcinomata was studied. The incidence of immunoglobulin labelled plasma cells (IgA and IgG) was twice as high in those cases of leukoplakia where dysplasia was present. The number of plasma cells, especially IgA- and IgG-containing plasma cells, decreased significantly with progressive tumor dedifferentiation. The plasma cell response differed before and after radiation with a decrease in IgA- and IgG-containing plasma cells after therapy. In contrast, bleomycin-therapy did not produce distinct changes in the humoral and cellular stromal reaction. In the epithelium, IgA and IgG were localized throughout all epithelial layers in leukoplakias with dysplasia. This finding indicates a leakage of locally synthesized immunoglobulins through an altered oral mucosa. This investigation reveals alterations in the local immune homoeostasis of the oral mucosa in premalignant and malignant lesions which varies with the grade of dysplasia, tumor differentiation and therapy.
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  • 5
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    Unknown
    Wiesbaden, etc. : Periodicals Archive Online (PAO)
    Hermes. 109 (1981) 280 
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  • 6
    ISSN: 1432-1335
    Keywords: Ovarian carcinoma ; p53 ; Metastasis ; Prognosis ; Ki67
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract p53 mutation and p53 protein overexpression are common findings in ovarian carcinomas. In order to evaluate the prognostic significance of the p53 status and its role in metastasis, we examined 104 ovarian carcinomas, among them 83 cases with follow-up data, and 40 pairs of primary tumors and metastases, by p53 immunohistochemistry and temperature-gradient gel electrophoresis. Comparison of primary tumors and their metastases revealed identical results in 88%–90% of the cases, indicating that, in most cases, mutantp53 occurs prior to metastatic spread and remains clonally conserved. With respect to all tumors, moderate/high p53 expression was significantly more prevalent in serous-papillary types, carcinomas with high grade, and high Ki67 scores, but was not associated with age, stage, or hormone receptor status. Kaplan-Meier analysis of 83 cases, followed-up for 9–96 months, demonstrated that moderate/high p53 overexpression in the group of 66 stage T3/M1 tumors was associated significantly (P=0.0028 andP=0.0105) with shorter overall and recurrence-free survival. Multivariate analysis revealed that advanced clinical stage and p53 positivity were the only independent predictive variables. No significance was seen in regard to second-look results and outcome of 50 patients receiving platinum-based chemotherapy. These observations show that p52 immunohistochemistry is an independent prognostic indicator at the given cut-off level, but does not reliably predict chemotherapy response.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1335
    Keywords: Key words Ovarian carcinoma ; p53 ; Metastasis ; Prognosis ; Ki67
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract p53 mutation and p53 protein overexpression are common findings in ovarian carcinomas. In order to evaluate the prognostic significance of the p53 status and its role in metastasis, we examined 104 ovarian carcinomas, among them 83 cases with follow-up data, and 40 pairs of primary tumors and metastases, by p53 immunohistochemistry and temperature-gradient gel electrophoresis. Comparison of primary tumors and their metastases revealed identical results in 88%–90% of the cases, indicating that, in most cases, mutant p53 occurs prior to metastatic spread and remains clonally conserved. With respect to all tumors, moderate/high p53 expression was significantly more prevalent in serous-papillary types, carcinomas with high grade, and high Ki67 scores, but was not associated with age, stage, or hormone receptor status. Kaplan-Meier analysis of 83 cases, followed-up for 9–96 months, demonstrated that moderate/high p53 overexpression in the group of 66 stage T3/M1 tumors was associated significantly (P = 0.0028 and P = 0.0105) with shorter overall and recurrence-free survival. Multivariate analysis revealed that advanced clinical stage and p53 positivity were the only independent predictive variables. No significance was seen in regard to second-look results and outcome of 50 patients receiving platinum-based chemotherapy. These observations show that p52 immunohistochemistry is an independent prognostic indicator at the given cut-off level, but does not reliably predict chemotherapy response.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2307
    Keywords: Oral mucosa ; Interepithelial cells ; Lymphocytes ; Langerhans cells ; Cerebriform cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im mehrschichtigen Plattenepithel der Mundschleimhaut finden sich neben den Keratinocyten auch nichtepitheliale mesenchymale und neuroektodermale, sog. interepitheliale Zellen, welche lichtmikroskopisch nur unzulänglich klassifizierbar sind. In der vorliegenden Studie wurde die Lippen-, Wangen- und Zungenschleimhaut von 50 Mäusen licht- und elektronenmikroskopisch untersucht. Dabei konnten 3 025 mononucleäre interepitheliale Zellen dokumentiert und analysiert werden. Monocytogene Makrophagen, Plasmazellen und Mastzellen waren interepithelial nicht nachweisbar und sind nicht als fester Bestandteil des Epithels anzusehen. Nur sehr wenige neuroektodermale Zellen — bei der Maus fast ausschließlich Merkelzellen und keine Melanocyten — liegen im Epithel. Die überwiegende Mehrzahl der interepithelialen Zellen sind Lymphocyten und Langerhanszellen als integrale Bestandteile des Epithels. 22,8% der gesamten interepithelialen Zellen erwiesen sich ultrastrukturell als Lymphocyten. Etwa je die Hälfte hiervon wiesen runde und gekerbte Kerne auf. Als zweite Gruppe von interepithelialen Zellen kommen die größeren dendritischen Langerhanszellen in der oralen Mucosa ebenso wie in allen anderen mehrschichtigen Plattenepithelien vor. 56,8% der interepithelialen Zellen können als Langerhanszellen eingestuft werden. Nicht alle cytologisch den Langerhanszellen entsprechenden Zellen enthalten Langerhansgranula. Diese können somit nicht als alleiniges Identifizierungsmerkmal gelten. Zwei Typen von Langerhanszellen können unterschieden werden. 80,9% haben das mehr oder weniger typische Erscheinungsbild, wie es von der Epidermis bekannt ist und wurden als makrophagocytoide Langerhanszellen bezeichnet. Die Kerne dieser Zellform sind unregelmäßig gekerbt und mäßig heterochromatinhaltig. 19,1% der Langerhanszellen besaßen auffällig große, runde euchromatische Kerne und ein helleres Cytoplasma. Diese werden als retikuloide Langerhanszellen bezeichnet. Etwa 20% der interepithelialen Zellen konnten weder Lymphocyten noch Langerhanszellen zugeordnet werden. Es waren kleine bis mittelgroße Zellen mit stark gekerbten „cerebriformen” heterochromatinreichen Kernen. Diese sind den sog. Sézary-Zellen und Mycosis fungoides Zellen der epidermotropen T-Zell-Lymphome ähnlich, deren lymphocytäre Natur gesichert ist. Auch uns erscheint eine Entwicklung dieser Zellen aus Lymphocyten im Epithel wahrscheinlich. Weiterhin wird diskutiert, ob die cerebriformen Zellen Vorstufen der Langerhanszellen darstellen. Eine solche Auffassung wird durch morphologische Zwischenstufen nahegelegt. Dies würde bedeuten, daß Langerhanszellen aus Lymphocyten entstehen, wobei die cerebriforme Zelle eine Zwischenstufe der Differenzierung darstellt. Möglicherweise spielt das mehrschichtige Plattenepithel hierbei eine Rolle für diese Zelldifferenzierung und erklärt die Epitheliotropie der Lymphocyten. Eine mögliche Identität von Langerhanszellen und interdigitierenden Retikulumzellen der T-Zellareale der Lymphknoten sowie eine enge funktionelle Kooperation von Langerhanszellen, Lymphocyten und interdigitierenden Reticulumzellen bei der immunologischen Abwehr externer Antigene werden diskutiert.
    Notes: Summary Non-epithelial mesenchymal and neuroectodermal cells occur between the keratinocytes in the stratified squamous epithelium of the oral mucosa. These cells cannot be classified adequately by light microscopy. In the present study the oral mucosa of the lip, cheek and tongue of 50 mice were studied by light and electron microscopy. 3,025 mononuclear interepithelial cells were documented and analysed. Monocytogenic macrophages, plasma cells and mast cells were not found interepithelially and cannot be regarded as a regular constituent of the epithelium. Only a few neuroectodermal cells — in mice these are exclusively Merkel cells, with no melanocytes — were localized in the epithelium. The majority of the interepithelial cell population is made up of lymphocytes (22.8%) and Langerhans cells (56.8%). They are an integral constituent of the epithelium. Lymphocytes with rounded and indented nuclei can be identified. The larger and dendritic Langerhans cells are a specific cell of squamous epithelium and also occur in the oral mucosa. Not all cells which feature the cytological characteristics of Langerhans cells contain Langerhans or Birbeck granules. Accordingly these granules cannot be considered an exclusive identification characteristic. Two types of Langerhans cells can be differentiated. 80.9% have the more or less typical appearance known from the epidermis and were termed macrophagocytoid Langerhans cells. The nuclei are irregularly indented and moderately heterochromatic. 19.1% possessed conspicuous large, spherical, euchromatic nuclei and an electron-lucent cytoplasm. These were termed reticuloid Langerhans cells. About 20% of the interepithelial cell population could not be identified, neither as typical lymphocytes nor as Langerhans cells. These were small to medium sized cells with deeply indented “cerebriform” strongly heterochromatic nuclei. They are similar to the “Sézary cells” or mycosis fungoides cells of epidermotropic human T-cell lymphomas. The lymphocytic nature of these cells has been confirmed. It seems likely that differentiation of lymphocytes to cerebriform cells occurs within the epithelium. It is further discussed whether cerebriform cells are precursors of Langerhans cells, a conclusion suggested morphologically by transitional forms. This would imply that Langerhans cells originate from lymphocytes, and that the cerebriform cell is an intermediate step of differentiation. The microenvironment of the squamous epithelium may play a role in the process of differentiation, which could explain the epitheliotropy of lymphocytes. The possibility is considered that Langerhans cells and interdigitating reticulum cells of the T-cell area of lymph nodes are identical. The close functional cooperation of Langerhans cells, lymphocytes, and interdigitating reticulum cells in immunological defenses against external antigens is discussed.
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  • 9
    ISSN: 1432-2307
    Keywords: Keratin polypeptides ; Epidermis ; Oral mucosa ; Epithelial differentiation ; Malignant transformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immune sera against total keratin and keratin polypeptide subunits were induced in guinea pigs, using the different bands of SDS polyacrylamide gel electrophoresis of fibrous proteins of stratum corneum, derived from normal human epidermis. The distribution of the different polypeptides was studied in numerous human biopsies of normal epidermis, normal oral mucosa and epidermal and mucosal inflammatory, premalignant and malignant lesions using the indirect immunoperoxidase method. Antisera against total keratin (TK) and against the keratin polypeptide of M.W. 55,000 dalton (55K) labelled all keratinocytes in normal and pathological conditions. These antisera may be useful for the histodifferentiation in diagnostic pathology. Atisera against the keratin polypeptides of M.W. 67,000 (67K) and 62,000 dalton (62K) identified only keratin antigens in the spinous, granular and keratinized layer of normal epidermis and oral mucosa. No labelling of the basal layer was achieved with these immune sera. However, there were important differences in the distribution of these keratin antigens in altered epithelia which may be of value in the differential diagnosis of inflammatory, premalignant and malignant lesions of the skin and oral mucosa.
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  • 10
    ISSN: 1432-2307
    Keywords: EBV infection ; Oral epithelia ; Hairy leukoplakia ; In situ hybridization ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty biopsies of oral mucosal lesions and normal oral mucosa were obtained from 26 HIV-seropositive individuals and studied for virus infections with Epstein-Barr virus-specific DNA probes (EBV). In situ DNA hybridization was carried out on frozen and formalin-fixed, paraffin-embedded tissues. Specifically bound biotinylated virus probes were detected with the streptavidin-gold-silver technique and visualized by standard and interference reflection microscopy. In 9/30 biopsies, EBV DNA was clearly demonstrated in the upper two thirds of oral epithelia. This finding corresponded to peculiar cytopathic effects including ground glass nuclei, basophilic nuclear inclusions, and ballooning of the cytoplasm, which were concentrated in the upper two or three layers of the stratum spinosum. Cytopathic effects together with the demonstration of EBV DNA were demonstrated in seven cases of tongue mucosa, and two cases derived from the gingiva. When comparing clinical and pathological findings with DNA detection rates, we saw 5/9 hairy leukoplakias associated with EBV infections. Four positive cases (two samples from the tongue, two gingival specimens) had not been regarded as hairy leukoplakia clinically. EBV infection of the oral epithelium occurred in male homosexuals (7 cases) and in male/ female intravenous drug abusers (2 cases). Among the nine EBV-positive cases, 2 patients were asymptomatic, 4 patients were grouped into the ARC-, and 3 individuals into the AIDS-category. We conclude that HIV-seropositive patients are particularly prone to develop productive EBV infections in oral epithelia. This infection most frequently appears at the lateral border of the tongue, but may also occur at other sites of the oral cavity, and may already exist in a preclinical stage prior to the development of oral white lesions (hairy leukoplakia).
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