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Biomedical subjects

S Pahl

Publications and source records attributed to S Pahl.

At least 19 recordsLinked to original sources

Expression of human Kallikrein 14 (KLK14) in breast cancer is associated with higher tumour grades and positive nodal status.

Human kallikrein 14 (KLK14) is a steroid hormone-regulated member of the tissue kallikrein family of serine proteases, for which a prognostic and diagnostic value in breast cancer has been suggested. To further characterise the value of KLK14 as a breast tumour marker, we have carefully analysed KLK14 expression in normal breast tissue and breast cancer both on the RNA level by real-time RT-PCR (n = 39), and on the protein level (n = 127) using a KLK14-specific antibody for immunohistochemistry. We correlated KLK14 protein expression data with available clinico-pathological parameters (mean follow-up time was 55 months) including patient prognosis. KLK14 RNA expression as quantified by real-time RT-PCR was significantly more abundant in breast tumours compared to normal breast tissue (P = 0.027), an issue that had not been clarified recently. Concordantly with the RNA data, cytoplasmic KLK14 protein expression was significantly higher in invasive breast carcinomas compared to normal breast tissues (P = 0.003). Furthermore, KLK14 protein expression was associated with higher tumour grade (P = 0.041) and positive nodal status (P = 0.045) but was not significantly associated with shortened disease-free or overall patient survival time in univariate analyses. We conclude that KLK14 is clearly overexpressed in breast cancer in comparison to normal breast tissues and is positively associated with conventional parameters of tumour aggressiveness, but due to a missing association with survival times, the use of KLK14 immunohistochemistry as a prognostic marker in breast cancer is questionable.

Adult↗

Polyploidization and centrosome hyperamplification in inflammatory bronchi.

OBJECTIVE AND DESIGN: Inflammatory and tumorous bronchi were screened in order to obtain new tumor relevant cytogenetic parameters. MATERIAL OR SUBJECTS: Bronchial cells of 32 patients were cultivated by standard cell culture procedures. METHODS: Tetraploidy and aneuploidy was determined by enumeration of chromosome 7 and 8 versus the number of centrosomes. The resulting data were correlated with histopathological data. RESULTS: Tetra- and aneuploidy of epithelial cells were detectable in 76% of tumor cell cultures, 75% of high grade inflammatory tissues and 40% of non- and low grade-inflammatory tissues. Additionally, we observed centrosome hyper-amplification and multipolar mitoses not only in the tumor but also in the early stages of inflammation. CONCLUSION: Inflammatory bronchi already show tumor-specific features and may consequently represent the preliminary genetic stage of cancer development in bronchi.

Adult↗

Thin section arrays for I-FISH analysis of chromosome-specific imbalances in squamous cell carcinomas of the head and neck.

Thin section arrays of 20 head and neck squamous cell carcinomas were studied by I-FISH for gains (including amplification) and losses of specific genomic segments. These arrays allow the examination not only of a number of tumor sections but also of the surrounding margins and of inconspicuous control tissue in one experiment. All tumor sections examined significantly differed from the inconspicuous control tissues by containing more or less extensive cell populations with aberrant signal constitutions. In no case, however, did the aberrant population constitute the whole area of the section. Gains of signals were strikingly more frequent than were losses. All tumors showed significant gains of the segments examined, the highest differences between tumor and control sections were found for the segments 9q34 and 8q24, followed by 5p15.3 and 11q13. Amplifications were most frequently found of 11q13: 8 of the 20 tumors showed amplifications in more than 20% of the nuclei, while no nucleus with more than four signals was found in any of the control tissues (control: 0%). Amplifications of the target sequences on chromosomes 8 (14 tumors) and 9 (8 tumors) were observed in low but significant percentages of nuclei, no significant cell population was detected with an amplification of 5p15.3. Fourteen tumors exhibited a significant loss of 13q14, and only 8 tumors a significant loss at any other site. In the tumor margin sections, in most cases, the margins apparently were also affected by the one or the other of the genomic changes of the pertinent primary tumor. Nevertheless, there were, in some cases, also large differences depending on the way of analysis, but also on the specific signal constitution considered. Tumor stages T3 and T4 tended to have higher frequency of nuclei with gains of 5p15.3, 8q24, and 11q13 as compared to T2 tumors and less gains of 9q34 and loss of 13q14. With the exception of 8q24 and 13q14 alterations there was also a trend to higher percentages of aberrant nuclei in the margin of T3-4 tumors vs. T2 tumors.

Aged↗

[Acinic cell carcinomas of the parotid gland. A retrospective analysis].

BACKGROUND AND OBJECTIVE: Acinic cell carcinoma of the parotid gland is a rare malignant tumor, which is generally regarded as low grade. However, rapidly fatal courses do occur. PATIENTS AND METHODS: Eighteen patients with acinic cell carcinoma were studied retrospectively who had undergone treatment between 1968 and 1997 at the University Ear, Nose, and Throat (ENT) Hospital in Homburg (Saar), Germany and between 1994 and 1997 at the Marienhospital ENT Hospital in Stuttgart, Germany. RESULTS: The distribution of the T category (UICC 1997) was as follows: T1 n = 8, T2 n = 7, T3 n = 1, and T4 n = 2). Treatment was exclusively surgical in 14 cases and a combination of surgery and postoperative radiotherapy in 4 cases. The recurrence rate according to Kaplan-Meier was 6% after 3 years and 19% after 5, 10, and 15 years. The survival rate was 87% after 3 years and 73% after 5, 10, and 15 years. None of the 12 patients with low-grade tumors according to Batsakis et al. (1979) died from the tumor, whereas survival at 5 years was only 33% for 6 high-grade tumors (p = 0.02). CONCLUSIONS: We recommend complete surgical removal of the tumor, in general by total parotidectomy. Postoperative radiotherapy may be useful in advanced high-grade tumors.

Adolescent↗

Patterns of cytokeratin expression in monkey and human periodontium following regenerative and conventional periodontal surgery.

The pattern of cytokeratin expression has been extensively described in the normal and inflamed periodontium. However, there is no information regarding the pattern of cytokeratin expression in the periodontium which has been reformed following regenerative periodontal surgery. The aim of the present investigation was to evaluate the pattern of cytokeratin expression in the reformed human and monkey periodontium following regenerative and conventional periodontal surgery. In 3 monkeys, acute fenestration-type and chronic intrabony defects were treated with guided tissue regeneration (GTR), enamel matrix proteins (EMD), or coronally repositioned flap surgery (control). After a healing period of 5 months, the animals were sacrificed and perfused with 10% buffered formalin for fixation. Specimens containing the defects and surrounding tissues were dissected free, decalcified in EDTA and embedded in paraffin. Histological sections were cut with the microtome set at 3 microm. The sections were alternatively stained either with hematoxylin and eosin, or immunohistochemically by using one of the broad range monoclonal antibodies 34betaE 12 (for cytokeratins 1, 5, 10 and 14) or KL 1 (for cytokeratins 1, 2, 5, 6, 7, 8, 10, 11, 16 and 19), or one of the individual monoclonal antibodies LL025 (for cytokeratin 16), DC 10 (for cytokeratin 18), A53-B/A2 (for cytokeratin 19). Twelve patients, each displaying one deep intrabony defect scheduled for extraction due to advanced periodontitis or prosthetic reasons, were treated as described above. Following a healing period of 6 months, the teeth were extracted together with some of their surrounding soft and hard tissues. The histological and immunohistochemical processing of the human biopsies was identical to that described in monkeys. The results revealed that both the normal non-treated (original) monkey and human junctional epithelium stained strongly with all of the monoclonal antibodies used. The reformed junctional epithelium displayed the same cytokeratin expression pattern as the non-treated junctional epithelium. No differences regarding the cytokeratin expression pattern of the junctional epithelium were found between the treatments and types of healing (i.e. regenerative, through a new periodontal ligament, or reparative through a long junctional epithelium). In the intact periodontal ligament, the epithelial rests of Malassez displayed a comparable cytokeratin expression pattern to that of the junctional epithelium. However, no expression of cytokeratins was seen in the newly formed periodontal ligament. In such specimens, cytokeratin expression was observed only until the borderline between the regenerated cementum and the epithelial downgrowth. It was concluded that: a) the reformed junctional epithelium, following any type of surgical procedure, displays a similar pattern of cytokeratin expression to the original junctional epithelium; b) in the newly formed periodontal ligament, no expression of cytokeratins is present; and c) the epithelial rests of Malassez do not seem to reform after regenerative periodontal surgery.

Alveolar Bone Loss↗

DNA amplification on chromosome 7q in squamous cell carcinoma of the tongue.

Squamous cell carcinoma of the head and neck exhibit a highly variable picture of chromosomal aberrations. In the present study the clearly defined anatomical region of the tongue was analyzed for potentially specific patterns of chromosomal alterations. Fresh tumor samples from 18 patients afflicted by squamous cell carcinoma of the tongue constituted the clinical basis of the present investigation. The tumor samples were analyzed on the basis of comparative genomic hybridization (CGH), a molecular cytogenetic FISH-approach. Gains in DNA copy numbers were detected as the predominant imbalance on chromosomes 7q (9/18), 3q (48/18), 16p (7/18) and 20q (7/18). The regions of minimal overlap on these chromosomes were mapped to 7q11.2q11.3 and 3q26. A conspicuous finding was the frequent detection of amplifications in the 7q11 region. Gains in the 7q region have been rarely reported in CGH studies of tumors derived from different regions of the head and neck. Amplifications on 7q could thus be specifically linked with the tongue region and could correlate with specific clinical factors of this tumor entity.

Adult↗

[Identification of a nasopharyngeal carcinoma using Epstein-Barr virus diagnosis].

We report the case of a 36-year-old women who was found to have a malignant tumor extending from the side of her right nasal cavity to the nasopharynx. Magnetic resonance imaging and computed tomography were not able to define the primary site of the tumor. Histologic evaluation demonstrated an undifferentiated squamous cell carcinoma. Because of the different treatment concepts for carcinomas of the nasal cavity and nasopharynx, we tried to identify the primary site by diagnosing Epstein-Barr virus (EBV) infection, which is associated with carcinoma of the nasopharynx. By using immunohistochemistry and polymerase chain reaction EBV could be identified in the cells of the carcinoma. This showed that the primary site of the tumor was located in the nasopharynx and resulted in the patient being treated with simultaneous radiochemotherapy.

Adult↗

[Diagnosis and therapy of pseudotumors of the orbits].

Orbital pseudotumor is a nonspecific inflammatory process of unknown etiology that can be divided histopathologically into three basic types: granulomatous, lymphoid, and sclerosing. Between 1995 and 1998, 12 patients with pseudotumor orbitae were treated in the ENT Department of the University of Saarland. Histopathological examination showed granulomatous type of pseudotumor in six, lymphoid in three, and sclerosing in three patients. In seven cases the pseudotumor orbitae were medially located and in four cases laterally. In one patient nearly all orbital structures were infiltrated. Diagnostic biopsy was taken endonasally in six cases, via medical orbitotomy in two cases, and via lateral orbitotomy in four cases. Due to their good delimitation lymphoid and sclerosing tumors were extracted completely during diagnostic biopsy and patients were free of complaints after a few weeks. The six patients with granulomatous pseudotumor were treated primarily with steroids after the diagnosis had been definitely confirmed by histology. In three of those six cases a second course of steroid therapy had to be given, with positive results in two cases. Follow-up was between 6 and 28 months (mean 16 months). There were no postoperative complications. The clinical and radiographic presentation of the pseudotumors can vary greatly. Therefore, the differential diagnosis of specific infections or neoplasms can only be established through diagnostic biopsy. Different rhinosurgical approaches provide clear biopsy results and in some cases the pseudotumor is even completely removed.

Adult↗

Malignant odontogenic myxoma of the maxilla: case with cytogenetic confirmation.

An odontogenic myxoma of the maxilla with an aggressive clinical course is presented. The tumour arose in a 53-year-old patient, recurred two times after extended maxillectomy and ultimately caused the patient's death by uncontrollable local disease with infiltration of the cranial cavity. Microscopically, the tumour showed histological features of a low grade malignant myxosarcoma with cellular areas, enhanced mitotic activity and nuclear pleomorphism. Cytogenetic analysis revealed an unexpectedly aberrant hypertetraploid chromosome complement, that was considered as incompatible with the usual karyotypic patterns of benign tumours.

Humans↗

A second primary intestinal-type adenocarcinoma of the sinonasal tract induced by wood dust.

Intestinal type adenocarcinoma of the sinonasal tract is associated with exposure to wood dust. We report the case of an adenocarcinoma tumor of the left sinonasal area diagnosed in 1998. Nineteen years earlier (1979), an intestinal type adenocarcinoma of the right nasal cavity was diagnosed. The first tumor was treated in 1979 surgically followed by postoperative radiotherapy. The second tumor showed the same histological features as an intestinal type adenocarcinoma (papillary type). The patient had a history of a 10 year exposure to wood dust (furniture worker), and the latency time of this patient was 48 years in 1998. We suppose that the tumor of the left side is a second primary intestinal type adenocarcinoma. This case indicates the usefulness of a lifelong follow up of patients with adenocarcinoma of the nose because of the wide range of latency times of these tumors.

Adenocarcinoma↗

[Hyper-IgE syndrome with ENT manifestations. Overview and case report of successful therapy with high dosage i.v. immunoglobulin].

Hyperimmunoglobulin E syndrome (Hiob syndrome or Buckley syndrome) is a rare disorder of the immune system that can show characteristic manifestations in the head and neck. Typical symptoms are fever, recurrent urticarial rashes, lymphadenitis, and bacterial infections of the skin and various parenchymatous organs. Diagnosis is established by elevated serum IgE concentrations with the absence of any signs of allergy or parasitic disease. We present our clinical experiences in managing of a 29-year old woman whose hyper IgE syndrome was diagnosed initially during of the treatment of lymphatic hyperplasia of the base of the tongue although she had typical symptoms of hyper IgE syndrome for some years. High-dose intravenous immunoglobulin therapy (IVIG) was found to be well-tolerated and effective. More than one year after a single course of immunoglobin therapy symptoms markedly improved. Current knowledge and therapeutic options in hyper IgE syndrome are discussed. We recommend that IVIG be considered as one of the first choices in the treatment of hyper IgE syndrome.

Adult↗

Expression analysis of genes at 3q26-q27 involved in frequent amplification in squamous cell lung carcinoma.

Gene amplifications are known to occur frequently in lung cancer. Recently, we identified gene amplifications at 3q26 in squamous cell lung carcinoma (SCC) using reverse chromosome painting. Here, our aim was to analyse the expression of genes which map within the amplified chromosomal region. The genes which were selected for their known function and their potential involvement in tumour development included the genes for ribosomal protein L22 (RPL22), butyrylcholinesterase (BCHE), glucose transporter 2 (SLC2A2), transferrin receptor (TFRC), thrombopoietin (THPO) and the phosphatidylinositol-3 kinase catalytic alpha polypeptide (PIK3CA). While five genes were expressed in the majority of the 17 samples of SCC, the gene for the glucose transporter 2 (SLC2A2) was expressed in only three cases, excluding SLC2A2 as the target gene of the amplification unit. For a subset of tumours, we determined the amplification status of the six genes. The TFRC, PIK3CA, BCHE, THPO and SLC2A2 genes were amplified in several cases, whereas the RPL22 gene was amplified in only one case. The combined amplification and expression data of this and our previous studies indicate that the amplified region at 3q26 contains several genes that are transcribed in SCC, providing the possibility that several amplified and functionally important genes at 3q26 may be involved in the pathogenesis of SCC.

Blotting, Southern↗