TY - JOUR AB - Background. SLC2A3 is upregulated in various cancer types and promotes proliferation, invasion, and metabolism. However, its role in the prognosis and immune regulation of head and neck squamous cell carcinoma (HNSCC) is still obscure. This study is aimed at exploring the prognostic and immunotherapeutic potential of SLC2A3 in HNSCC. Methods. All data were downloaded from TCGA database and integrated via R software. SLC2A3 expression was evaluated using R software, TIMER, CPTAC, and HPA databases. The association between SLC2A3 expression and clinicopathologic characteristics was assessed by R software. The effect of SLC2A3 on survival was analyzed by R software and Kaplan-Meier Plotter. Genomic alterations in SLC2A3 were investigated using the cBioPortal database. Coexpression of SLC2A3 was studied using LinkedOmics and STRING, and enrichment analyses were performed with R software. The relationship between SLC2A3 expression and immune infiltration was determined using TIMER and TISIDB databases. Immune checkpoints and ESTIMATE score were analyzed via the SangerBox database. Results. SLC2A3 expression was upregulated in HNSCC tissues compared to normal tissues. It was significantly related to TNM stage, histological grade, and alcohol history. High SLC2A3 expression was associated with poor prognosis in HNSCC. Coexpression analysis indicated that SLC2A3 mostly participated in the HIF-1 signaling pathway and glycolysis. Furthermore, SLC2A3 expression strongly correlated with tumor-infiltrating lymphocytes in HNSCC. Conclusion. SLC2A3 could serve as a potential prognostic biomarker for tumor immune infiltration in HNSCC. AU - Chu, M.K.* AU - Zheng, K.* AU - Li, X.* AU - Luo, Z.* AU - Yang, X. AU - Wei, C.* C1 - 66411 C2 - 52810 TI - Comprehensive analysis of the role of SLC2A3 on prognosis and immune infiltration in head and neck squamous cell carcinoma. JO - Anal. Cell. Pathol. VL - 2022 PY - 2022 SN - 0921-8912 ER - TY - JOUR AB - Cell type specific radial positioning of chromosome territories (CTs) and their sub-domains in the interphase seem to have functional relevance in non-neoplastic human nuclei, while much less is known about nuclear architecture in carcinoma cells and its development during tumor progression. We analyzed the 3D-architecture of the chromosome 8 territory (CT8) in carcinoma and corresponding non-neoplastic ductal pancreatic epithelium. Fluorescence-in-situ-hybridization (FISH) with whole chromosome painting (WCP) probes on sections from formalin-fixed, paraffin wax-embedded tissues from six patients with ductal adenocarcinoma of the pancreas was used. Radial positions and shape parameters of CT8 were analyzed by 3D-microscopy. None of the parameters showed significant inter-individual changes. CT8 was localized in the nuclear periphery in carcinoma cells and normal ductal epithelial cells. Normalized volume and surface of CT8 did not differ significantly. In contrast, the normalized roundness was significantly lower in carcinoma cells, implying an elongation of neoplastic cell nuclei. Unexpectedly, radial positioning of CT8, a dominant parameter of nuclear architecture, did not change significantly when comparing neoplastic with non-neoplastic cells. A significant deformation of CT8, however, accompanies nuclear atypia of carcinoma cells. This decreased roundness of CTs may reflect the genomic and transcriptional alterations in carcinoma. AU - Timme, S.* AU - Schmitt, E.* AU - Stein, S.* AU - Schwarz-Finsterle, J.* AU - Wagner, J.* AU - Walch, A.K. AU - Werner, M.* AU - Hausmann, M.* AU - Wiech, T.* C1 - 5605 C2 - 28830 SP - 21-33 TI - Nuclear position and shape deformation of chromosome 8 territories in pancreatic ductal adenocarcinoma. JO - Anal. Cell. Pathol. VL - 34 IS - 1-2 PB - IOS Press PY - 2011 SN - 0921-8912 ER - TY - JOUR AB - Feature extraction is a crucial step in most cytometry studies. In this paper a systematic approach to feature extraction is presented. The feature sets that have been developed and used for quantitative cytology at the Laboratory for Biomedical Image Analysis of the GSF as well as at the Center for Image Analysis in Uppsala over the last 25 years are described and illustrated. The feature sets described are divided into morphometric, densitometric, textural and structural features. The latter group is used to describe the eu‐ and hetero‐chromatin in a way complementing the textural methods. The main goal of the paper is to bring attention to the need of a common and well defined description of features used in cyto‐ and histometrical studies. The application of the sets of features is shown in an overview of projects from different fields. Finally some rules of thumb for the design of studies in this field are proposed. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐1/rodenacker.htm. AU - Rodenacker, K. AU - Bengtsson, E.* C1 - 22145 C2 - 20835 SP - 1-36 TI - A feature set for cytometry on digitized microscopic images. JO - Anal. Cell. Pathol. VL - 25 IS - 1 PY - 2003 SN - 0921-8912 ER - TY - JOUR AB - Multiple chromosomal imbalances have been identified in breast cancer using comparative genomic hybridization (CGH). Their association with the primary tumors' potential for building distant metastases is unknown. In this study we have investigated 39 invasive breast carcinomas with a mean follow-up period of 99 months (max. 193 months) by CGH to determine the prognostic value of chromosomal gains and losses.The mean number of chromosomal imbalances per tumor was 6.5+/-0.7 (range 2 to 18). The most frequent alterations identified in more than 1/3 of cases were gains on chromosomes 11q13, 12q24, 16, 17, and 20q, and losses on 2q and 13q. A significantly different frequency of chromosomal aberrations (pless than or equal to0.05) was found between DNA-diploid and non-diploid tumors (gain on chromosome 17). Differences were also noted between tumors progressing to distant metastases within the period of follow-up and those which do not (gains on 11q13 and 12q24; loss on 12q).Significant univariate correlations (pless than or equal to0.05) with the metastasis-free survival of patients were found for lymph node status, the cytometrical determined DNA ploidy (diploid/non-diploid) and anisokaryosis, and for DNA gains on 11q13, 12q24, 17, and 18p. An unexpected inverse correlation was found between clinical outcome and gains on 11q13 and 12q24.In multivariate analysis independent prognostic value, in addition to lymph node status, was found for chromosomal gains on 11q13, 12q24, 17 and 18p. Amplification on 20q, which did not correlate with metastasis-free survival in a univariate analysis, showed weak prognostic significance in combination with the nodal status.The prognostic value of chromosomal alterations - some of them by inverse correlation - suggests an interaction and/or compensation of the involved amplified genes and their effects on the occurrence of distant metastases in breast cancer patients. AU - Aubele, M. AU - Auer, G.* AU - Braselmann, H.* AU - Nährig, J.* AU - Zitzelsberger, H.* AU - Quintanilla-Martinez, L. AU - Smida, J.* AU - Höfler, H. AU - Werner, M.* C1 - 10378 C2 - 20370 SP - 77-87 TI - Chromosomal imbalances are associated with metastasis-free survival in breast cancer patients. JO - Anal. Cell. Pathol. VL - 24 IS - 2-3 PB - IOS Press PY - 2002 SN - 0921-8912 ER - TY - JOUR AB - The hypothetical multistep model of breast carcinogenesis suggests a transition from normal epithelium to invasive carcinoma via intraductal hyperplasia (without and with atypia) and in situcarcinoma. These presumptive precursor lesions are currently defined by their histological features, and their prognosis is imprecisely estimated from indirect epidemiological evidence. Cytogenetic and molecular‐genetic analysis of these lesions give evidence for an accumulation of various genetic alterations during breast tumorigenesis. Using immuno‐histochemistry overexpression of the c‐erbB‐2 oncogene was found in ductal carcinoma in situ(DCIS), but not in atypical intraductal hyperplasia (AIDH) and intraductal hyperplasia (IDH). An expression of mutant p53 tumor suppressor gene as well as expression of cyclin D1 was identified in DCIS. In IDH lesions loss of heterozygosity (LOH) at various loci could be identified, and comparative genomic hybridization (CGH) and fluorescence in situhybridization (FISH) studies delivered evidence for DNA amplification on chromosomal region 20q13 in the early stage of IDH. However, little is currently known about genetic alterations in those premalignant lesions, and the chronology of genetic alterations and histopathological changes during carcinogenesis is mainly undiscovered. Figure 1 can be viewed in colour on http://www.esacp.org/acp/2002/24‐23/aubele.htm AU - Aubele, M. AU - Werner, M.* AU - Höfler, H. C1 - 22016 C2 - 20567 SP - 69-76 TI - Genetic alterations in presumptive precursor lesions of breast carcinomas. JO - Anal. Cell. Pathol. VL - 24 IS - 2-3 PY - 2002 SN - 0921-8912 ER - TY - JOUR AB - There is evidence that breast cancer is a heterogeneous disease phenotypically as well as molecular biologically. So far, heterogeneity on the molecular biological level has not been investigated in potential precursor lesions, such as ductal hyperplasia (DH) and ductal carcinoma in situ (DCIS). In this study we applied comparative genomic hybridization (CGH) to formalin-fixed, paraffin-embedded breast tissue with DH and DCIS, adjacent to invasive ductal carcinoma (IDC), to screen these potential precursor lesions for whole genomic chromosomal imbalances. Laser-microdissection was used to select pure cell populations from the sections. Isolated DNA was amplified by degenerate oligonucleotide primed PCR (DOP-PCR) and further processed for CGH analysis. Investigating multiple samples (n = 25) from four patients we found an average of 5.6 +/- 0.9 (mean +/- SEM) chromosomal imbalances already present in DH. In the twelve DCIS lesions an average of 10.8 (+/- 0.9) aberrations was identified with 14.8 (+/- 0.8) aberrations in the four adjacent IDC lesions. The increasing number of chromosomal changes in parallel with the histopathological sequence corroborate the hypothesis, that the carcinomas may have developed through a sequential progression from normal to proliferative epithelium and eventually into carcinoma. However, heterogeneous results were identified in the multiple samples per entity from the same patient, demonstrated mainly in the DCIS samples in the chromosomal regions 6p, 9p, 11q, 16p and 17q, in the DH samples by 3p, 16p and 17q. This heterogeneous findings were most pronounced within the DH and was less in the DCIS and IDC samples. The only aberration consistently found in all samples-even in all DH sample-was amplification of the 20q13 region. Our results demonstrate, that the applied combination of laser-microdissection, DOP-PCR and CGH, may serve to analyse breast carcinogenesis pathways in suitable histological material. However, so far, it is unclear how to handle heterogeneous results and these make identification of relevant changes more difficult. Setting a threshold and evaluating only those chromosomal changes which are present in a majority of samples may be one possibility. This involves however, the risk that infrequent but possibly significant aberrations may be missed. Figures on http://www.esacp.org/acp/2000/20-1/aubele. htm. AU - Aubele, M. AU - Cummings, M.* AU - Walch, A.K. AU - Zitzelsberger, H. AU - Nährig, J.* AU - Höfler, H. AU - Werner, M.* C1 - 23362 C2 - 31120 SP - 17-24 TI - Heterogeneous chromosomal aberrations in intraductal breast lesions adjacent to invasive carcinoma. JO - Anal. Cell. Pathol. VL - 20 IS - 1 PB - IOS Press PY - 2000 SN - 0921-8912 ER - TY - JOUR AB - Neuroendocrine tumours (NET) of the lung are divided in subtypes with different malignant potential. The first is the benign or low‐grade malignant tumours, well‐differentiated, called typical carcinoids (TC) and the second is the high‐grade malignant tumours, poorly differentiated of small (SCLC) or large cell type (LCLC). Between these tumour types lies the well‐differentiated carcinoma with a lower grade of malignancy (WDNEC). In clinical routine it is very important with regard to prognosis to distinguish patients with low malignant potential from those with higher ones. In this study 32 cases of SCLC, 13 of WDNEC and 14 of TC with a follow‐up time up to 7 years were collected. Sections 4 μm thick from paraffin embedded tissue were Feulgen stained. By means of high resolution image analysis 100 nuclei per case were randomly gathered to extract morphometric, densitometric and textural quantitative features. To investigate the ploidy status of the tumour the corrected DNA distribution was calculated. Stepwise linear discriminant analysis to differentiate the classes and Cox regression analysis for the survival time analysis were applied. Using chromatin textural and morphometric features in two two‐class discriminations, 11 of the 14 TC cases and 8 of the 13 WDNEC cases were correctly classified and 11/13 WDNEC cases and 28/32 SCLC cases, respectively. The WDNEC cases are more similar in chromatin structure to TC than to SCLC. For the survival analysis, only chromatin features were selected to differentiate patients with better and worse prognosis independent of staging and tumour type. AU - Jütting, U. AU - Gais, P. AU - Rodenacker, K. AU - Böhm, J.* AU - Koch, S. AU - Präuer, H.W.* AU - Höfler, H. C1 - 21018 C2 - 19068 SP - 109-119 TI - Diagnosis and prognosis of neuroendocrine tumours of the lung by means of high resolution image analysis. JO - Anal. Cell. Pathol. VL - 18 IS - 2 PY - 1999 SN - 0921-8912 ER - TY - JOUR AB - Highly sensitive and inexpensive methods that are not time consuming are desirable for monitoring the workplace environment for the detection of cytotoxic hazards, particularly cancerous risks. It is possible to detect precancerous and cancerous lesions in samples taken by brushing the nose, but the cytological diagnoses can be affected by an inability to obtain representative smears from the sometimes very small focal lesions, and uncertainties in the subjective interpretation of suspicious cells when these are small in number. In an attempt to improve diagnosis we applied imaging cytometry (ICM) and tested the concept of malignancyassociated changes (MAC) in routinely Papanicolaou-stained smears. Cells of non-goblet type that visually appeared normal were selected from nickel workers with and without dysplastic lesions of the nasal mucosa. A set of nuclear features was measured by ICM and used for discriminant analysis. We were able to differentiate between workers with non-dysplastic normal and suspicious mucosa smears and those with dysplastic lesions. Unexpectedly, it was found possible to distinguish between workers in the roasting/smelting and the electrolysis departments, who were exposed to different carcinogenic nickel compounds. A further surprising finding was the possibility to distinguish smokers and non-smokers among the nickel workers. AU - Reith, A.K.* AU - Reichborn-Kjennerud, S.* AU - Aubele, M. AU - Jütting, U. AU - Gais, P. AU - Burger, G.T. C1 - 39989 C2 - 35185 SP - 9-21 TI - Biological monitoring of chemical exposure in nickel workers by imaging cytometry (ICM) of nasal smears. JO - Anal. Cell. Pathol. VL - 6 IS - 1 PY - 1994 SN - 0921-8912 ER - TY - JOUR AB - The chromosomes from a methotrexate (MTX)-resistant and its parental V79,B7 Chinese hamster cell line were analysed by the combined use of flow karyotyping and sorting, metaphase analysis and in situ hybridization with a probe for the dihydrofolate reductase (DHFR) gene responsible for methotrexate resistance. A marker chromosome with an elongated arm carrying the amplified DHFR gene was identified by in situ hybridization of metaphase cells of the methotrexate-resistant line. In the flow karyotype the marker chromosome was found as an additional peak with a higher DNA content compared with the largest chromosome of the sensitive line. This was additionally verified by G-banding of the chromosomes sorted from the marker peak. Several other chromosomal rearrangements not associated with the amplified gene could be identified in the methotrexate-resistant line by the combined use of flow karyotyping and metaphase analysis. The fate of the original marker chromosome was studied in cells growing several weeks in the absence of methotrexate, comparing flow karyotyping and metaphase analysis. The original marker chromosome was lost in about 50% of the cells after 5 weeks and in about 60% of the cells after 8 weeks; between 80 and 90% of the cells, however, contained marker chromosomes of various sizes. The MTX-resistance decreased in parallel during loss of the original marker chromosome. In conclusion, the study shows that the power of cytogenetic analysis is improved by the combined use of conventional cytogenetics, molecular cytogenetics and flow cytometry. AU - Nüsse, M. AU - Viaggi, S. AU - Bonatti, S. C1 - 40512 C2 - 34371 SP - 345-358 TI - Identification and fate of a marker chromosome in methotrexate-resistant V79,B7 cells by flow karyotyping and sorting, metaphase analysis and in situ hybridization. JO - Anal. Cell. Pathol. VL - 4 IS - 5 PY - 1992 SN - 0921-8912 ER - TY - JOUR AU - Burger, G. C1 - 19343 C2 - 12422 TI - Cytometric Measures for the Diagnostic Support in Breast Cancer Pathology. JO - Anal. Cell. Pathol. PY - 1991 SN - 0921-8912 ER - TY - JOUR AU - Aubele, M. AU - Guttenberger, R. AU - Gais, P. A2 - Burger, G.* C1 - 18539 C2 - 11127 SP - 309 TI - Morphological Changes in Murine Lymphocytes and Vaginal Cells during Experimental Tumorigenesis. JO - Anal. Cell. Pathol. IS - 1 (5-6) PB - Amsterdam : Excerpta Medica PY - 1990 SN - 0921-8912 ER - TY - JOUR AU - Nüsse, M. AU - Viaggi, S. AU - Bonatti, S. A2 - Burger, G.* C1 - 19597 C2 - 12706 CY - Amsterdam SP - 302 TI - Identification of Marker Chromosomes in PALA Resistant Cell Clones by Flow Karyotyping and Sorting, Metaphase Analysis and in Situ Hybridization. JO - Anal. Cell. Pathol. IS - 1(5-6) PB - Elsevier Science Publishers PY - 1990 SN - 0921-8912 ER - TY - JOUR AU - Burger, G. AU - Jütting, U. AU - Aubele, M. AU - Auer, G. A2 - Burger, G.* C1 - 19596 C2 - 12705 SP - 286 TI - The Role of High Resolution Cytometry in the Prognosis of Breast Cancer. JO - Anal. Cell. Pathol. IS - 1(5-6) PB - Amsterdam : Excerpta Medica PY - 1989 SN - 0921-8912 ER - TY - JOUR AU - Höfler, H. A2 - Burger, G.* C1 - 19598 C2 - 12707 SP - 324 TI - Simultaneous in Situ Hybridization and Immunohistochemistry. JO - Anal. Cell. Pathol. IS - 1 (5-6) PB - Amsterdam : Excerpta Medica PY - 1989 SN - 0921-8912 ER -