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Biomedical subjects

Katharina Glatz-Krieger

Publications and source records attributed to Katharina Glatz-Krieger.

6 recordsLinked to original sources

Anatomic site-specific patterns of gene copy number gains in skin, mucosal, and uveal melanomas detected by fluorescence in situ hybridization.

To assess the differences between melanomas of different location and different etiology, 372 malignant melanomas were brought in a tissue microarray format. The collection included 23 acral and 118 non-acral skin melanomas, 9 mucosal melanomas, 100 uveal melanomas, and 122 melanoma metastases. Fluorescence in situ hybridization (FISH) was used to assess copy number changes of the cyclin D1 (CCND1), MDM2, c-myc (MYC), and HER2 genes. FISH analysis revealed distinct differences between melanomas from different locations. CCND1 amplifications were detected in skin melanomas from sites with chronic sun exposure (6 of 32 cases), acral melanomas (4 of 17 cases), and mucosal melanomas (one of ten cases) but not in uveal melanomas. High-level MDM2 amplifications were exclusively present in acral melanomas (2 of 19 cases). MYC copy number gains were detected in 32 of 71 uveal melanomas, five of eight mucosal melanomas, and 6 of 67 melanomas from sites with intermittent sun exposure but not in acral melanomas nor melanomas from sites with chronic sun exposure. Alterations of the MYC gene were associated with advanced tumor stage. There were no high-level HER2 amplifications. Site-specific genetic and epigenetic features may impact the response of melanomas to various anti-cancer drugs and should be considered in future studies on the molecular pathogenesis of malignant melanomas.

Biomarkers, Tumor↗

Factors to keep in mind when introducing virtual microscopy.

Digitization of glass slides and delivery of so-called virtual slides (VS) emulating a real microscope over the Internet have become reality due to recent improvements in technology. We have implemented a virtual microscope for instruction of medical students and for continuing medical education. Up to 30,000 images per slide are captured using a microscope with an automated stage. The images are post-processed and then served by a plain hypertext transfer protocol (http)-server. A virtual slide client (vMic) based on Macromedia's Flash MX, a highly accepted technology available on every modern Web browser, has been developed. All necessary virtual slide parameters are stored in an XML file together with the image. Evaluation of the courses by questionnaire indicated that most students and many but not all pathologists regard virtual slides as an adequate replacement for traditional slides. All our virtual slides are publicly accessible over the World Wide Web (WWW) at http://vmic.unibas.ch . Recently, several commercially available virtual slide acquisition systems (VSAS) have been developed that use various technologies to acquire and distribute virtual slides. These systems differ in speed, image quality, compatibility, viewer functionalities and price. This paper gives an overview of the factors to keep in mind when introducing virtual microscopy.

Education, Medical, Continuing↗

Expression of sex hormone receptors and cell cycle proteins in melanocytic lesions of the ocular conjunctiva.

BACKGROUND: Both dermal and ocular melanocytic nevi have been reported to undergo changes during pregnancy. This has been proposed to be related to hormonal influences; however, few studies have provided any proof. We therefore set out to evaluate the expression of sex hormone receptors and cell cycle proteins in melanocytic lesions of the ocular conjunctiva. METHODS: Formalin-fixed, paraffin-embedded material from 76 tumors--69 conjunctival nevi, 5 specimens of primary acquired melanosis (PAM), and 2 conjunctival melanomas--were included in a tissue microarray (TMA) format. The TMA sections were analyzed by immunohistochemistry with antibodies for progesterone and estrogen receptors, and cell cycle-related proteins (p16, MIB1-Ki67). RESULTS: Progesterone receptors were highly (96%) and similarly expressed in all lesions. In addition, progesterone receptor expression showed a tendency to increase with age (p=0.06). In contrast, estrogen receptor expression was completely absent in all tumors. The cell cycle regulator p16 was expressed in 97% of the lesions. The proliferation marker MIB1-Ki67 was expressed at low levels (mean+/-SD: 13+/-14%) in 79% of the lesions. No differences of expression were found between the different lesions and nevi types. The mean age of the patients was highest in conjunctival melanoma (70+/-22 years), followed by PAM (60+/-19 years) and nevi (36+/-18 SD years). The different types of nevi also showed significant age dependency (junctional 25+/-17 years, compound 34+/-17 years, dermal 49+/-15 years). CONCLUSION: Our findings reveal the expression of progesterone, but not estrogen, in melanocytic lesions of the ocular conjunctiva. In benign conjunctival lesions, p16 and MIB1-Ki67 expression was comparable to that in benign nevi of the skin.

Adolescent↗

Acute renal failure on immune reconstitution in an HIV-positive patient with miliary tuberculosis.

Immune reconstitution syndrome following HAART in human immunodeficiency virus (HIV)-infected patients is characterized by inflammatory worsening of organ functions despite improvement in HIV surrogate markers of HIV infection. We describe a patient with miliary tuberculosis and urinary shedding of acid fast bacilli who developed acute renal failure 8 weeks after initiation of antituberculosis therapy and 6 weeks after initiation of HAART. The diagnostic workup and further course of disease implicated immune reconstitution syndrome as the cause of acute renal failure.

Acute Kidney Injury↗

Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance.

PURPOSE: CEACAM6, CEACAM1, and human carcinoembryonic antigen (CEA) are coexpressed in normal colorectal epithelia, but show deregulated expression in colorectal cancers (CRC). Upregulation of CEACAM6 expression in hyperplastic polyps and early adenomas represents one of the earliest observable molecular events leading to colorectal tumors. The aim of our study was to evaluate the prognostic relevance of CEACAM6, CEACAM1, and CEA tissue expression in patients with CRC. PATIENTS AND METHODS: Immunohistochemical analysis was carried out on tissue microarrays from 243 paraffin-embedded biopsies from a randomized controlled clinical trial (Swiss Group for Clinical Cancer Research [SAKK] 40/81) of adjuvant fluorouracil-based chemotherapy with CEACAM-specific monoclonal antibodies. The median follow-up was 8 years. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier estimates and hazard ratios (HRs) estimated using Cox proportional hazards models. RESULTS: Tissue expression of CEACAM6, CEACAM1, and CEA was enhanced in 55%, 58%, and 94% of patients, respectively. Multivariate Cox analysis including sex, age, tumor site, stage, differentiation grade, treatment, and nodal status as covariates showed that CEACAM6 overexpression independently predicted poor OS (HR, 1.86; P =.0100) and DFS (HR, 2.00; P =.0028), whereas CEACAM1 or CEA were not significantly related to these outcomes. The data did not provide evidence for or against the hypothesis that the CEACAM6 effect on survival differs according to treatment. CONCLUSION: Expression of the cell adhesion molecule CEACAM6 in CRC is an independent prognostic factor allowing subdivision of patients into low- and high-risk groups. Whether CEACAM6 or CEA and CEACAM1 might be useful as predictive markers of chemotherapy benefit remains unclear.

Adenocarcinoma↗

Virtual slides: high-quality demand, physical limitations, and affordability.

Virtual slides (VSs) have been around since the beginning of telepathology. As recently as a couple of years ago, only single small images could be acquired, and their distribution was limited to e-mail at best. Today, whole slides can be acquired, covering an area up to 100,000 times larger than that possible only a few years ago. Moreover, advanced Internet and world-wide web technologies enable delivery of those images to a broad audience. Despite considerable advances in technology, few good examples of VSs for public use can be found on the web. One of the reasons for this is a lack of sophisticated and integrated commercial solutions covering the needs from acquisition to delivery at reasonable cost. This article describes physical and technical limitations of the VS technology to clarify the demands on a VS acquisition system. A new type of web-based VS viewer (vMic; http://alf3.urz.unibas.ch/vmic/) open to public use is introduced, allowing anyone to set up a VS system with high usability at low cost.

Humans↗